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Sodium cyanoborohydride → 3-Bromo-N-((2S)-2-(4-fluorophenyl)-4-{3-[(9aS)-4-oxohexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]azetidin-1-yl}butyl)-N-methyl-5-(trifluoromethyl)benzamide

HRID 2063299
ノート
印刷プレビュー

反応式

HRID 2063299 の反応式
Cl.Cl.[Br:3][C:4]1[CH:5]=[C:6]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[C:7]([N:9]([CH2:11][C@H:12]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[CH2:13][CH2:14][N:15]1[CH2:18][CH:17]([N:19]2[CH2:24][CH2:23][N:22]3[C:25](=[O:29])[CH2:26]C[CH2:28][CH:21]3[CH2:20]2)[CH2:16]1)[CH3:10])=[O:8].N1CC(N2CCN3[C@H](C[O:52]CC3=O)C2)C1.C([BH3-])#N.[Na+]>C(O)C.CO.[Cl-].[Zn+2].[Cl-]>[Br:3][C:4]1[CH:5]=[C:6]([CH:37]=[C:38]([C:40]([F:42])([F:41])[F:43])[CH:39]=1)[C:7]([N:9]([CH2:11][C@H:12]([C:30]1[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=1)[CH2:13][CH2:14][N:15]1[CH2:18][CH:17]([N:19]2[CH2:24][CH2:23][N:22]3[C@H:21]([CH2:28][O:52][CH2:26][C:25]3=[O:29])[CH2:20]2)[CH2:16]1)[CH3:10])=[O:8]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 5003444Sodium cyanoborohydrideHCID 16124476(9aS)-8-azetidin-3-ylhexahydropyrazino[2,1-c][1,4]oxazin-4(3H)-oneHCID 866483133-Bromo-N-{(2S)-2-(4-fluorophenyl)-4-[3-(6-oxooctahydro-2H-pyrido[1,2-a]pyrazin-2-yl)azetidin-1-yl]butyl}-N-methyl-5-(trifluoromethyl)benzamide dihydrochloride

生成物 1

HCID 596128753-Bromo-N-((2S)-2-(4-fluorophenyl)-4-{3-[(9aS)-4-oxohexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]azetidin-1-yl}butyl)-N-methyl-5-(trifluoromethyl)benzamide
収率 62.4%

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 702Ethanol溶媒HCID 887Methanol溶媒

実験手順

To a solution of 3-bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide (see Method 3; 100 mg, 0.22 mmol) and (9aS)-8-azetidin-3-ylhexahydropyrazino[2,1-c][1,4]oxazin-4(3H)-one (see Method 12; ˜0.20 mmol) in ethanol (20 mL) was added a solution of sodium cyano borohydride (125 mg, 2.0 mmol) and zinc chloride (135 mg, 0.99 mmol) in methanol (10 mL). The reaction mixture was stirred at RT for 10 min and then the solvent was removed by evaporation. The residue was partitioned between ethyl acetate (50 mL) and water (20 mL). The organic solution was washed with brine and then dried over Na2SO4. The solvent was removed by evaporation and the residue was dissolved in a mixture of acetonitrile (10 mL), acetic acid (100 mg) and water (20 mL). The product was purified by means of reversed phase chromatography using a mixture of acetonitrile and aqueous 0.1 M ammonium acetate. The proper fractions were combined and concentrated on a rotavapor. The aqueous residue was extracted with ethyl acetate and the organic solution was dried over Na2SO4. The solvent was removed by evaporation. There was obtained 80 mg (55%) of the title compound. 1H NMR (400 MHz, CDCl3): 0.9-3.8 (cm, 21.5H), 3.9 (d, 1H), 4.1-4.2 (qt, 2H), 4.4 (b, 0.5H), 4.5-4.6 (d, 1H), 6.6-7.5 (cm, 6H), 7.8 (s, 1H); LCMS: m/z 642 (M+1)+.

後処理

  1. customthe solvent was removed by evaporation
  2. customThe residue was partitioned between ethyl acetate (50 mL) and water (20 mL)
  3. washThe organic solution was washed with brine
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed by evaporation
  6. dissolutionthe residue was dissolved in a mixture of acetonitrile (10 mL), acetic acid (100 mg) and water (20 mL)
  7. customThe product was purified by means of reversed phase chromatography
  8. additiona mixture of acetonitrile and aqueous 0.1 M ammonium acetate
  9. concentrationconcentrated on a rotavapor
  10. extractionThe aqueous residue was extracted with ethyl acetate
  11. dry with materialthe organic solution was dried over Na2SO4
  12. customThe solvent was removed by evaporation

出典と根拠

ORDレコード
ord-42077c7ef2544d7bb4f90a4be36cd8d8
出典データセット
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08288370B2

反応ノート

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