Sodium hydride → 4-{6-Bromo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine

HRID 1398573Notes

Reaction equation

HRID 1398573 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[O:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH2:28])[N:23]=1>CN(C=O)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[O:12])=[N:7][N:8]2[C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH2:28])[N:23]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2233322-Amino-4-chloropyrimidineHCID 681818546-bromo-3-[(morpholin-4-yl)carbonyl]-1H-indazole

Product 1

HCID 681816314-{6-Bromo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-bromo-3-[(morpholin-4-yl)carbonyl]-1H-indazole (78%, 458 mg, 1.15 mmol) in DMF (8 mL) was added NaH (60% oil suspension, 73.71 mg, 1.84 mmol) at 0° C. Mixture was stirred at RT for 10 minutes before addition of 4-chloropyrimidin-2-amine (298.44 mg, 2.3 mmol). The mixture was stirred at RT for 10 minutes and then at 65° C. for 5 hr. Reaction mixture was quenched by addition of water (5 mL) and a little EtOAc (2 mL) was added. Precipitate formed was collected and dried under vacuum to give the title compound: 1H NMR (500 MHz, DMSO) delta 3.58-3.80 (6H, m), 3.87-4.13 (2H, m), 7.07 (1H, d, J=5.52 Hz), 7.59 (1H, dd, J=8.51, 1.42 Hz), 7.94 (1H, d, J=8.83 Hz), 8.35 (1H, d, J=5.52 Hz), 9.19 (1H, d, J=1.26 Hz); LC-MS: m/z=+404.8 (M+H)+.

Workup

  1. waitat 65° C. for 5 hr
  2. customReaction mixture
  3. customwas quenched by addition of water (5 mL)
  4. additiona little EtOAc (2 mL) was added
  5. customPrecipitate formed
  6. customwas collected
  7. customdried under vacuum

Sources & evidence

ORD record
ord-1e775331d92b492dbdce4524be8ba4ad
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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