Sodium cyanoborohydride → HCID 68650966, compound

HRID 646717Notes

Reaction equation

HRID 646717 reaction equation
[NH2:1][C:2]1[C:3]([C:16]([NH:18][CH3:19])=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=O)[CH:9]=2)=[CH:6][N:7]=1.[NH2:20][CH:21]1[C:29]2[C:24](=[C:25]([F:31])[CH:26]=[CH:27][C:28]=2[F:30])[CH2:23][CH2:22]1.[C:32]([BH3-])#N.[Na+]>C1COCC1.C(O)(=O)C>[NH2:1][C:2]1[C:3]([C:16]([NH:18][CH3:19])=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][NH:20][CH:21]3[C:29]4[C:24](=[C:25]([F:31])[CH:26]=[CH:27][C:28]=4[F:30])[CH:23]([CH3:32])[CH2:22]3)[CH:9]=2)=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 584399044,7-Difluoro-2,3-dihydro-1H-inden-1-amineHCID 58710602HCID 58710602, compound

Product 1

HCID 68650966HCID 68650966, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide (50 mg, 0.19 mmol) and 1-amino-4,7-difluoroindane (67.6 mg, 0.4 mmol) in THF (5 mL) was added sodium cyanoborohydride (62.8 mg, 1 mmol) and 1 drop of acetic acid. The solution was stirred overnight and solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (50 mL) and saturated aqueous solution of Na2CO3 (10 mL). The phases were separated. The organic layer was washed with HCl (5 mL 0.5 M) then saturated aqueous sodium chloride and dried (Na2SO4). Filtration and concentration follow by hplc purification gave (42.2 mg, 50% yield) of 3-amino-6-(3-{[(4,7-difluoro-3-methyl-2,3-dihydro-1H-inden-1-yl)amino]methyl}phenyl)-N-methylpyrazine-2-carboxamide. An excess of HCl in dioxane (0.2 mL, 4.0 M) was added to the solution and the solvent was removed to give hydrochloride: 1H NMR (400 MHz; DMSO-d6): 10.1 (br s, 1H); 9.7 (br s, 1H); 9.0 (m, 1H); 8.85 (s, 1H); 8.2 (m, 1H); 7.5 (m, 2H); 7.3-7.2 (m, 2H); 5.0 (m, 1H); 4.6-4.15 (m, 3H); 3.4 (m, 1H); 2.95 (m, 1H); 2.85 (d, 3H); 2.6 (m, 1H); 2.46 (m, 1H); MS (EI) for C22H21N50F2 HCl: 410 (MH+).

Workup

  1. customsolvent was removed under reduced pressure
  2. customThe residue was partitioned between ethyl acetate (50 mL) and saturated aqueous solution of Na2CO3 (10 mL)
  3. customThe phases were separated
  4. washThe organic layer was washed with HCl (5 mL 0.5 M)
  5. dry with materialsaturated aqueous sodium chloride and dried (Na2SO4)
  6. filtrationFiltration and concentration
  7. customfollow by hplc purification

Sources & evidence

ORD record
ord-b8b7715a2bf947d29063a24d04a0f8a7
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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