Sodium Bicarbonate → (3S)-3-(aminomethyl)-3-cyclopropyl-1-(2-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyrrolidin-2-one

HRID 714908Notes

Reaction equation

HRID 714908 reaction equation
[CH:1]1([C@:4]2([C:27]#[N:28])[CH2:8][CH2:7][N:6]([C:9]3[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]4[CH:17]=[N:18][N:19]([C:21]([CH3:25])([CH3:24])[CH2:22][OH:23])[CH:20]=4)[N:10]=3)[C:5]2=[O:26])[CH2:3][CH2:2]1.[BH4-].[Na+].C(=O)([O-])O.[Na+]>CO.O.O.O.O.O.O.[Co](Cl)Cl>[NH2:28][CH2:27][C@@:4]1([CH:1]2[CH2:3][CH2:2]2)[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[N:18][N:19]([C:21]([CH3:25])([CH3:24])[CH2:22][OH:23])[CH:20]=3)[N:10]=2)[C:5]1=[O:26]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 71741336(3S)-3-cyclopropyl-1-(2-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 117841033(3S)-3-(aminomethyl)-3-cyclopropyl-1-(2-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyrrolidin-2-oneYield 20.8%

Reagents, catalysts & solvents 2

HCID 517166Dichlorocobalt hexahydrateCatalystHCID 887MethanolSolvent

Procedure

To a solution of (3S)-3-cyclopropyl-1-(2-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile (400 mg) obtained in Step I of Example 103 and cobalt(II) chloride hexahydrate (1.0 g) in methanol (6.0 mL) was added sodium borohydride (400 mg), and the mixture was stirred at room temperature for 4 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution in an ice bath, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to give the title compound (84 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe obtained organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol)

Sources & evidence

ORD record
ord-8d8f62c591d645f1bc7cfe50c20cf7a4
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

Loading…