Acetic Acid → 3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide

HRID 646713Notes

Reaction equation

HRID 646713 reaction equation
[NH2:1][C:2]1[C:3]([C:23]([NH:25][CH3:26])=[O:24])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][CH2:17][CH:18]3[CH2:22][CH2:21][CH2:20][NH:19]3)=[O:15])[CH:9]=2)=[CH:6][N:7]=1.[CH:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[NH2:1][C:2]1[C:3]([C:23]([NH:25][CH3:26])=[O:24])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][CH2:17][CH:18]3[CH2:22][CH2:21][CH2:20][N:19]3[CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:15])[CH:9]=2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 686509073-amino-N-methyl-6-(3-{[(pyrrolidin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide

Product 1

HCID 686520823-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamideYield 225%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 3-amino-N-methyl-6-(3-{[(pyrrolidin-2-ylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide (35.4 mg, 0.01 mmol) and benzaldehyde (24.8 mg, 0.02 mmol) in methanol (3 mL) was added sodium cyanoborohydride (25 mg, 0.04 mmol). The mixture was stirred for 1 h and then acetic acid added until the pH of the solution was 7.0. The solution was stirred for an additional 6 h, solvent was removed and residue was partitioned with CHCl3 and 2 M aqueous sodium hydroxide (5 mL). The aqueous phase was extracted with additional CHCl3 (2×5 mL) and the combined organic layer were washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate. Filtration, concentration and column chromatography provided 10 mg of 3-amino-N-methyl-6-{3-[({[1-(phenylmethyl)pyrrolidin-2-yl]methyl}amino)carbonyl]phenyl}pyrazine-2-carboxamide: 1H NMR (400 MHz; CDCl3); 8.7 (s, 1H); 8.65 (s, 1H); 8.28 (br s, 1H); 7.95 (d, 1H); 7.22 (d, 1H); 7.53 (t, 1H); 7.2-7.4 (m, 5H); 4.3-3.5 (m, 7H); 2.95 (d, 3H); 2.35-1.8 (m, 4H); MS (EI) for C25H28N6O2: 445 )

Workup

  1. stirringThe solution was stirred for an additional 6 h
  2. customsolvent was removed
  3. customresidue was partitioned with CHCl3 and 2 M aqueous sodium hydroxide (5 mL)
  4. extractionThe aqueous phase was extracted with additional CHCl3 (2×5 mL)
  5. washthe combined organic layer were washed with saturated aqueous sodium chloride
  6. dry with materialthen dried over anhydrous sodium sulfate
  7. filtrationFiltration, concentration and column chromatography

Sources & evidence

ORD record
ord-5ca01a6cf71344f8ab71297fbc6d45bf
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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