tert-Butyl 3-amino-5-bromo-1H-indazole-1-carboxyl­ate

Thiruvalluvar, A.A.; Kusanur, R.; Sridharan, M.

doi:10.1107/S2414314621006945

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 6| Part 7| July 2021| x210694

https://doi.org/10.1107/S2414314621006945

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tert-Butyl 3-amino-5-bromo-1H-indazole-1-carboxylate

Aravazhi Amalan Thiruvalluvar,^a ^* Raviraj Kusanur ^b and Makuteswaran Sridharan ^b

^aPrincipal (Retired), Kunthavai Naacchiyaar Government Arts College for Women (Autonomous), Thanjavur 613 007, Tamilnadu, India, and ^bDepartment of Chemistry, RV College of Engineering, Bangalore 560 059, Karnataka, India
^*Correspondence e-mail: thiruvalluvar.a@gmail.com

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 30 June 2021; accepted 6 July 2021; online 9 July 2021)

In the title compound, C₁₂H₁₄BrN₃O₂, the pyrazole and benzene rings are nearly co-planar with a dihedral angle between the rings of 2.36 (5)°. In the crystal, inversion dimers linked by pairwise N—H⋯N hydrogen bonds generate R₂²(8) loops. The dimers are linked into a three-dimensional network by weak aromatic π–π stacking interactions [centroid–centroid separation = 3.7394 (6) Å] and C—H⋯O and C—H⋯Br hydrogen bonds.

Keywords: crystal structure; 1H-indazole; inversion dimer.

CCDC reference: 2094667

Structure description

Indazole derivatives possess pharmacological properties against infectious, neurodegenerative and inflammatory disorders and are also good anti-microbial agents (e.g., Kusanur & Mahesh, 2013 ). To generate a library of compounds using 3-amino-6-bromo indazole, the boc protection of the ring NH group was carried out to form the title compound. From the crystal data, it is confirmed that, as expected, the boc protection happened only at the ring NH grouping.

In this structure (Fig. 1), the fused pyrazole (N1/N2/C7/C6/C1) and benzene (C1–C6) rings are nearly co-planar, subtending a dihedral angle of 2.36 (5)°. The dihedral angle between the C8/O1/O2 ester group and the fused-ring system is 10.01 (4)°. One of the methyl groups (C10) of the tert-butyl substituent lies close to the ester-group plane [displacement = −0.068 (1) Å], whereas C11 and C12 are displaced above and below it. Very weak C2—H2⋯O2, C11—H11C⋯O2 and C12—H12B⋯O2 intramolecular interactions are present (Table 1).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯O2	0.95	2.46	2.9609 (13)	113
C11—H11C⋯O2	0.98	2.38	2.9559 (15)	117
C12—H12B⋯O2	0.98	2.46	3.0475 (15)	118
N3—H3B⋯N2ⁱ	0.865 (18)	2.165 (19)	3.0249 (12)	172.8 (16)
C2—H2⋯O2ⁱⁱ	0.95	2.62	3.4133 (12)	141
C5—H5⋯Br1ⁱⁱⁱ	0.95	3.11	3.8871 (10)	140
C12—H12A⋯O2^iv	0.98	2.62	3.5582 (14)	161
Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

Figure 1
A view of the structure of the title compound with displacement ellipsoids drawn at the 70% probability level.

In the extended structure, pairwise N3—H3B⋯N2 links form centrosymmetric dimers with an R₂²(8) ring motif (Fig. 2). The dimers are linked into a three-dimensional network by C2—H2⋯O2, C5—H5⋯Br1 and C12—H12A⋯O2 hydrogen bonds and a π–π stacking interaction (Fig. 3) also occurs with Cg1⋯Cg1(2 − x, 1 − y, −z) = 3.7394 (6) Å, where Cg1 is the centroid of the pyrazole ring.

Figure 2
Partial packing viewed along b-axis direction showing the R₂²(8) ring motif.

Figure 3
A view of the π–π interaction along the a-axis direction.

Synthesis and crystallization

5-Bromo-1H-indazol-3-amine (1): To a solution of 5-bromo-2-fluoro benzonitrile (1.0 mmol) in ethanol (20 ml) was added hydrazine hydrate (99%) (10.0 mmol). The reaction mixture was heated in sealed tube at 343 K for 4 h and progress of the reaction was monitored by TLC. The reaction mixture was concentrated to dryness. The brown-coloured solid was purified by recrystallization from ethanol solution to afford pale-yellow needles (90%), m.p. 407 K (Fig. 4).

Figure 4
Synthesis scheme for the title compound.

tert-Butyl 3-amino-5-bromo-1H-indazole-1-carboxylate (2): To a solution of compound (1) (5.0 mmol) in dichloromethane (40 ml) was added DMAP (5.0 mmol). The reaction mixture cooled to 273 K and boc anhydride (5.0 mmol) was added. The reaction mixture was slowly warmed to room temperature and stirred for 15 h. Progress of the reaction was monitored by TLC. The reaction mixture was diluted with dichloromethane (50 ml) and washed with water and brine (25 ml), dried over anhydrous sodium sulfate and concentrated. The crude compound was purified by column chromatography (silica gel, 20–30% ethyl acetate in hexane) to afford a gummy solid, which solidifies as transparent crystals after 2 d (62%), m.p. 389 K.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₁₄BrN₃O₂
M_r	312.17
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	100
a, b, c (Å)	5.8281 (2), 10.5313 (3), 11.0917 (3)
α, β, γ (°)	85.954 (1), 78.801 (2), 75.105 (1)
V (Å³)	645.23 (3)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	3.18
Crystal size (mm)	0.45 × 0.32 × 0.30

Data collection
Diffractometer	Bruker SMART APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2012 )
T_min, T_max	0.502, 0.748
No. of measured, independent and observed [I > 2σ(I)] reflections	19603, 7076, 5872
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.895

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.027, 0.070, 1.08
No. of reflections	7076
No. of parameters	174
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.59, −0.53
Computer programs: APEX2 and SAINT (Bruker, 2012), SHELXS97 (Sheldrick, 2008 ), SHELXL2018/3 (Sheldrick, 2015 ), ORTEP-3 for Windows (Farrugia, 2012 ), PLATON (Spek, 2020 ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 2094667

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314621006945/hb4388sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314621006945/hb4388Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314621006945/hb4388Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2414314621006945/hb4388Isup4.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2020); software used to prepare material for publication: SHELXL2018/3 (Sheldrick, 2015), PLATON (Spek, 2020) and publCIF (Westrip, 2010).

tert-Butyl 3-amino-5-bromo-1H-indazole-1-carboxylate top

Crystal data top

C₁₂H₁₄BrN₃O₂	F(000) = 316
M_r = 312.17	D_x = 1.607 Mg m⁻³
Triclinic, P1	Melting point: 389 K
a = 5.8281 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.5313 (3) Å	Cell parameters from 2120 reflections
c = 11.0917 (3) Å	θ = 2.7–25.5°
α = 85.954 (1)°	µ = 3.18 mm⁻¹
β = 78.801 (2)°	T = 100 K
γ = 75.105 (1)°	Fragment, colourless
V = 645.23 (3) Å³	0.45 × 0.32 × 0.30 mm
Z = 2

Data collection top

Bruker SMART APEXII CCD diffractometer	5872 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.018
Absorption correction: multi-scan (SADABS; Bruker, 2012)	θ_max = 39.5°, θ_min = 1.9°
T_min = 0.502, T_max = 0.748	h = −10→10
19603 measured reflections	k = −18→18
7076 independent reflections	l = −19→19

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.027	Hydrogen site location: mixed
wR(F²) = 0.070	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	w = 1/[σ²(F_o²) + (0.0327P)² + 0.1773P] where P = (F_o² + 2F_c²)/3
7076 reflections	(Δ/σ)_max = 0.002
174 parameters	Δρ_max = 0.59 e Å⁻³
0 restraints	Δρ_min = −0.53 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. The amino –NH₂ H atoms were located in a difference Fourier map and their positions were freely refined. The C-bound H atoms were placed in calculated positions (C—H = 0.95–0.98 Å) and were refined with U_iso(H) = 1.2U_eq(C) or 1.5U_eq(methyl C).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.90907 (17)	0.59306 (9)	0.21941 (9)	0.01265 (14)
C2	1.04771 (18)	0.62182 (10)	0.29904 (9)	0.01532 (16)
H2	1.063744	0.574273	0.374242	0.018*
C3	1.16027 (19)	0.72288 (10)	0.26285 (10)	0.01661 (17)
H3	1.255405	0.745757	0.314333	0.020*
C4	1.13572 (18)	0.79194 (10)	0.15122 (10)	0.01534 (16)
C5	1.00073 (18)	0.76403 (10)	0.07169 (9)	0.01467 (16)
H5	0.987132	0.811006	−0.003982	0.018*
C6	0.88544 (17)	0.66311 (9)	0.10852 (9)	0.01246 (14)
C7	0.73941 (17)	0.60237 (9)	0.05102 (9)	0.01226 (14)
C8	0.76837 (18)	0.40037 (10)	0.31328 (9)	0.01421 (15)
C9	0.61429 (18)	0.20590 (10)	0.36754 (9)	0.01514 (16)
C10	0.5067 (2)	0.12827 (12)	0.29308 (11)	0.0236 (2)
H10A	0.356430	0.184090	0.272305	0.035*
H10B	0.472695	0.051548	0.341495	0.035*
H10C	0.621570	0.099056	0.217351	0.035*
C11	0.8457 (2)	0.11997 (11)	0.40268 (11)	0.02108 (19)
H11A	0.963638	0.090441	0.328004	0.032*
H11B	0.810398	0.043417	0.450934	0.032*
H11C	0.912110	0.170719	0.451721	0.032*
C12	0.4299 (2)	0.26645 (12)	0.47786 (11)	0.0218 (2)
H12A	0.285095	0.320478	0.450072	0.033*
H12B	0.498911	0.321461	0.521026	0.033*
H12C	0.386670	0.196475	0.533695	0.033*
Br1	1.30179 (2)	0.92671 (2)	0.10637 (2)	0.01982 (3)
N1	0.78125 (15)	0.49788 (8)	0.22385 (8)	0.01335 (13)
N2	0.67956 (15)	0.50413 (8)	0.11849 (7)	0.01299 (13)
N3	0.67793 (17)	0.63640 (9)	−0.06185 (8)	0.01576 (15)
O1	0.66674 (15)	0.31183 (8)	0.27930 (7)	0.01632 (13)
O2	0.84393 (16)	0.40048 (8)	0.40767 (7)	0.01973 (15)
H3A	0.669 (3)	0.7159 (19)	−0.0811 (17)	0.029 (5)*
H3B	0.575 (3)	0.6006 (17)	−0.0839 (16)	0.025 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0122 (4)	0.0141 (4)	0.0128 (3)	−0.0042 (3)	−0.0033 (3)	−0.0017 (3)
C2	0.0155 (4)	0.0186 (4)	0.0141 (4)	−0.0059 (3)	−0.0051 (3)	−0.0017 (3)
C3	0.0160 (4)	0.0194 (4)	0.0172 (4)	−0.0068 (3)	−0.0054 (3)	−0.0041 (3)
C4	0.0148 (4)	0.0145 (4)	0.0181 (4)	−0.0059 (3)	−0.0020 (3)	−0.0031 (3)
C5	0.0160 (4)	0.0137 (4)	0.0156 (4)	−0.0059 (3)	−0.0031 (3)	−0.0004 (3)
C6	0.0123 (4)	0.0132 (4)	0.0131 (3)	−0.0039 (3)	−0.0038 (3)	−0.0009 (3)
C7	0.0119 (3)	0.0136 (4)	0.0124 (3)	−0.0042 (3)	−0.0032 (3)	−0.0006 (3)
C8	0.0144 (4)	0.0157 (4)	0.0136 (4)	−0.0049 (3)	−0.0041 (3)	0.0008 (3)
C9	0.0158 (4)	0.0163 (4)	0.0147 (4)	−0.0065 (3)	−0.0044 (3)	0.0039 (3)
C10	0.0311 (6)	0.0252 (5)	0.0218 (5)	−0.0178 (4)	−0.0103 (4)	0.0064 (4)
C11	0.0169 (4)	0.0192 (4)	0.0260 (5)	−0.0022 (3)	−0.0055 (4)	0.0031 (4)
C12	0.0161 (4)	0.0275 (5)	0.0193 (4)	−0.0035 (4)	−0.0008 (4)	0.0033 (4)
Br1	0.01951 (5)	0.01624 (5)	0.02640 (6)	−0.00958 (4)	−0.00275 (4)	−0.00328 (4)
N1	0.0151 (3)	0.0157 (3)	0.0120 (3)	−0.0067 (3)	−0.0058 (3)	0.0013 (3)
N2	0.0140 (3)	0.0156 (3)	0.0115 (3)	−0.0055 (3)	−0.0052 (3)	0.0005 (3)
N3	0.0205 (4)	0.0166 (4)	0.0136 (3)	−0.0080 (3)	−0.0077 (3)	0.0022 (3)
O1	0.0216 (3)	0.0177 (3)	0.0137 (3)	−0.0105 (3)	−0.0069 (3)	0.0039 (2)
O2	0.0260 (4)	0.0218 (4)	0.0159 (3)	−0.0096 (3)	−0.0111 (3)	0.0037 (3)

Geometric parameters (Å, º) top

C1—N1	1.3874 (12)	C9—O1	1.4835 (12)
C1—C6	1.4006 (13)	C9—C10	1.5177 (15)
C1—C2	1.4019 (13)	C9—C12	1.5185 (16)
C2—C3	1.3859 (15)	C9—C11	1.5222 (15)
C2—H2	0.9500	C10—H10A	0.9800
C3—C4	1.4039 (15)	C10—H10B	0.9800
C3—H3	0.9500	C10—H10C	0.9800
C4—C5	1.3815 (14)	C11—H11A	0.9800
C4—Br1	1.9021 (10)	C11—H11B	0.9800
C5—C6	1.3954 (13)	C11—H11C	0.9800
C5—H5	0.9500	C12—H12A	0.9800
C6—C7	1.4453 (13)	C12—H12B	0.9800
C7—N2	1.3141 (12)	C12—H12C	0.9800
C7—N3	1.3671 (12)	N1—N2	1.3998 (11)
C8—O2	1.2122 (12)	N3—H3A	0.840 (19)
C8—O1	1.3351 (12)	N3—H3B	0.865 (18)
C8—N1	1.3824 (13)

N1—C1—C6	106.05 (8)	C10—C9—C11	110.23 (10)
N1—C1—C2	132.33 (9)	C12—C9—C11	112.91 (9)
C6—C1—C2	121.59 (9)	C9—C10—H10A	109.5
C3—C2—C1	116.85 (9)	C9—C10—H10B	109.5
C3—C2—H2	121.6	H10A—C10—H10B	109.5
C1—C2—H2	121.6	C9—C10—H10C	109.5
C2—C3—C4	120.95 (9)	H10A—C10—H10C	109.5
C2—C3—H3	119.5	H10B—C10—H10C	109.5
C4—C3—H3	119.5	C9—C11—H11A	109.5
C5—C4—C3	122.74 (9)	C9—C11—H11B	109.5
C5—C4—Br1	118.85 (8)	H11A—C11—H11B	109.5
C3—C4—Br1	118.40 (7)	C9—C11—H11C	109.5
C4—C5—C6	116.38 (9)	H11A—C11—H11C	109.5
C4—C5—H5	121.8	H11B—C11—H11C	109.5
C6—C5—H5	121.8	C9—C12—H12A	109.5
C5—C6—C1	121.49 (8)	C9—C12—H12B	109.5
C5—C6—C7	133.15 (9)	H12A—C12—H12B	109.5
C1—C6—C7	105.28 (8)	C9—C12—H12C	109.5
N2—C7—N3	122.92 (9)	H12A—C12—H12C	109.5
N2—C7—C6	111.54 (8)	H12B—C12—H12C	109.5
N3—C7—C6	125.46 (9)	C8—N1—C1	126.18 (8)
O2—C8—O1	127.43 (9)	C8—N1—N2	122.33 (8)
O2—C8—N1	121.75 (9)	C1—N1—N2	111.27 (8)
O1—C8—N1	110.82 (8)	C7—N2—N1	105.85 (8)
O1—C9—C10	102.25 (8)	C7—N3—H3A	113.2 (13)
O1—C9—C12	109.28 (9)	C7—N3—H3B	118.0 (12)
C10—C9—C12	110.83 (9)	H3A—N3—H3B	117.7 (17)
O1—C9—C11	110.84 (8)	C8—O1—C9	119.35 (8)

N1—C1—C2—C3	177.48 (10)	O2—C8—N1—C1	10.52 (16)
C6—C1—C2—C3	0.02 (15)	O1—C8—N1—C1	−169.07 (9)
C1—C2—C3—C4	−0.25 (15)	O2—C8—N1—N2	−175.37 (10)
C2—C3—C4—C5	−0.10 (16)	O1—C8—N1—N2	5.04 (13)
C2—C3—C4—Br1	−178.60 (8)	C6—C1—N1—C8	175.41 (9)
C3—C4—C5—C6	0.68 (15)	C2—C1—N1—C8	−2.34 (17)
Br1—C4—C5—C6	179.17 (7)	C6—C1—N1—N2	0.75 (11)
C4—C5—C6—C1	−0.91 (14)	C2—C1—N1—N2	−177.00 (10)
C4—C5—C6—C7	−177.26 (10)	N3—C7—N2—N1	177.97 (9)
N1—C1—C6—C5	−177.46 (9)	C6—C7—N2—N1	0.84 (11)
C2—C1—C6—C5	0.59 (15)	C8—N1—N2—C7	−175.90 (9)
N1—C1—C6—C7	−0.22 (10)	C1—N1—N2—C7	−1.00 (11)
C2—C1—C6—C7	177.83 (9)	O2—C8—O1—C9	6.31 (16)
C5—C6—C7—N2	176.37 (10)	N1—C8—O1—C9	−174.13 (8)
C1—C6—C7—N2	−0.41 (11)	C10—C9—O1—C8	−179.09 (9)
C5—C6—C7—N3	−0.68 (18)	C12—C9—O1—C8	63.43 (12)
C1—C6—C7—N3	−177.45 (9)	C11—C9—O1—C8	−61.63 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O2	0.95	2.46	2.9609 (13)	113
C11—H11C···O2	0.98	2.38	2.9559 (15)	117
C12—H12B···O2	0.98	2.46	3.0475 (15)	118
N3—H3B···N2ⁱ	0.865 (18)	2.165 (19)	3.0249 (12)	172.8 (16)
C2—H2···O2ⁱⁱ	0.95	2.62	3.4133 (12)	141
C5—H5···Br1ⁱⁱⁱ	0.95	3.11	3.8871 (10)	140
C12—H12A···O2^iv	0.98	2.62	3.5582 (14)	161

Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x+2, −y+1, −z+1; (iii) −x+2, −y+2, −z; (iv) x−1, y, z.

Acknowledgements

MS thanks the academic and administrative authorities of RV College of Engineering for their support and encouragement. The authors are grateful to Dr M. Zeller for the single-crystal X-ray diffraction data.

References

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