Sodium cyanoborohydride → HCID 68650966、化合物

HRID 646717ノート

反応式

HRID 646717 の反応式
[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

参加物

6

反応物 3

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

生成物 1

HCID 68650966HCID 68650966、化合物収率 52.5%

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 8028Tetrahydrofuran溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-b8b7715a2bf947d29063a24d04a0f8a7
出典データセット
uspto-grants-2010_04
特許番号
US07704995B2

反応ノート

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