Sodium borohydride → HCID 46892495, compound

HRID 1801899Notes

Reaction equation

HRID 1801899 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][C:14]([C:27]([F:30])([F:29])[F:28])=[CH:15][CH:16]=3)[N:11]=2)=[O:9])=[CH:4][CH:3]=1.[BH4-].[Na+]>O.CO.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][C:14]([C:27]([F:30])([F:28])[F:29])=[CH:15][CH:16]=3)[N:11]=2)[OH:9])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 46892494HCID 46892494, compound

Product 1

HCID 46892495HCID 46892495, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To (4-fluorophenyl) (4-(5-methyl-1H-pyrazol-3-ylamino)-7-(trifluoromethyl)quinazolin-2-yl) methanone (500 mg, 1.2 mmol) in a 1:1 mixture of MeOH/THF (10 mL) at 0° C. was added NaBH4 (68 mg, 1,79 mmol). After 10 min of stirring at 0° C., 10 drops of water were added. The solvents were removed under vacuum and the residue was dissolved in a mixture of 1:1 of water EtOAc (20 mL), washed with brine and dried over sodium sulfate. The crude product (360 mg) was purified on reverse-phase preparative HPLC (elution gradient of 40-90% acetonitrile in water with 0.05% acetic acid) to afford (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)-7-(trifluoromethyl)quinazolin-2-yl)methanol as white solid (140 mg, 40%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.2 (s, 3 H) 5.9(s, 1H) 6.55 (s, 1 H) 7.35-7.5(m, 3H) 7.9-8.0(m, 1H) 8.05-8.3 (m, 4H) 11.1 (br. s, 1 H) 12.25 (br. s., 1 H) LC-MS (ESI) m/z 418 (M+H)+.

Workup

  1. customThe solvents were removed under vacuum
  2. dissolutionthe residue was dissolved in a mixture of 1:1 of water EtOAc (20 mL)
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. customThe crude product (360 mg) was purified on reverse-phase preparative HPLC (elution gradient of 40-90% acetonitrile in water with 0.05% acetic acid)

Sources & evidence

ORD record
ord-fc2c1bed0713442e8aa5fddf08201e03
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

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