Sodium hydride → HCID 178509490, compound

HRID 1398490Notes

Reaction equation

HRID 1398490 reaction equation
Cl[CH:2]1[NH:7][C:6]([NH2:8])=[N:5][CH:4]=[C:3]1[N+:9]([O-:11])=[O:10].[H-].[Na+].[NH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]#[N:24])[CH:21]=2)[CH:16]=[N:15]1>CN(C=O)C>[NH2:8][C:6]1[NH:7][CH:2]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]#[N:24])[CH:21]=3)[CH:16]=[N:15]2)[C:3]([N+:9]([O-:11])=[O:10])=[CH:4][N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 4225291H-indazole-6-carbonitrileHCID 178508523HCID 178508523, compound

Product 1

HCID 178509490HCID 178509490, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-chloro-5-nitro-1,6-dihydropyrimidin-2-amine (538.5 mg, 60% purity, 2.00 mmol) in DMF (10 mL) was added NaH (60% oil suspension, 172 mg, 4.30 mmol) at 0° C. Mixture was stirred at RT for 10 min before addition of 1H-indazole-6-carbonitrile (410 mg, 2.87 mmol). Stirring was continued at RT for 18 hr. The reaction mixture was quenched with water (25 mL) cooled in an ice bath and extracted with EtOAc (3×20 mL). Insoluble solid formed during extraction was separated out. Combined EtOAc extract was washed with water (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. A portion (70 mg) of the crude product was purified by reverse phase preparative HPLC to give the title compound: 1H NMR (250 MHz, DMSO) δ 7.79 (1 H, dd, J=8.22, 1.07 Hz), 8.14 (1H, d, J=8.22 Hz), 8.20 (1H, br. s.), 8.33 (1H, br. s.), 8.65 (1H, s), 8.91 (1H, s), 9.03 (1H, s); LC-MS: m/z=+281.95 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with water (25 mL)
  2. temperaturecooled in an ice bath
  3. extractionextracted with EtOAc (3×20 mL)
  4. customInsoluble solid formed during extraction
  5. customwas separated out
  6. extractionCombined EtOAc extract
  7. washwas washed with water (20 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customA portion (70 mg) of the crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-95557195f6cf49499890de38052fe0aa
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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