Sodium hydride → 1-(2-aminopyrimidin-4-yl)-6-bromo-N,N-dimethylindazole-3-carboxamide

HRID 1398570Notes

Reaction equation

[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([NH2:25])[N:20]=1>CN(C=O)C>[NH2:25][C:21]1[N:22]=[C:23]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=3)[C:6]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[N:7]2)[CH:24]=[CH:19][N:20]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 6-bromo-N,N-dimethyl-1H-indazole-3-carboxamide (95%, 450 mg, 1.59 mmol) in DMF (10 mL) was added NaH (60% dispension in mineral oil) (60 mg, 1.02 mmol) at 0° C. Mixture was stirred at rt for 10 mins before addition of 4-chloropyrimidin-2-amine (413 mg, 3.19 mmol). The mixture was stirred at 65° C. overnight. The mixture was quenched by addition of water (10 mL). The mixture was extracted with EtOAc (2×15 mL). The combined organics washed with water (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. Trituration with DCM:heptane (4:1) gave the desired product. The filtrate was re-filtered. The solids were combined to give the title compound; 1H NMR (250 MHz, DMSO) delta 3.11 (3H, s), 3.32 (3H, s), 7.08 (1H, d, J=5.48 Hz), 7.19 (1H, d, J=3.35 Hz), 7.58 (1H, dd, J=8.68, 1.68 Hz), 7.95 (1H, d, J=8.53 Hz), 8.34 (1H, d, J=5.63 Hz), 9.18 (1H, d, J=1.22 Hz); LC-MS: m/z=+362.8 (M+H)+.

Workup

customThe mixture was quenched by addition of water (10 mL)
extractionThe mixture was extracted with EtOAc (2×15 mL)
washThe combined organics washed with water (10 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-017ea8594fa241b7b6af597ee95e2e57
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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