Sodium cyanoborohydride → HCID 68650966, 화합물

HRID 646717노트

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HRID 646717 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

HCID 68650966HCID 68650966, 화합물수율 52.5%

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 8028Tetrahydrofuran용매

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-b8b7715a2bf947d29063a24d04a0f8a7
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07704995B2

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