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Diisopropylethylamine → N-[(2S)-4-{3-[4-(Azetidin-1-ylcarbonyl)piperidin-1-yl]azetidin-1-yl}-2-(4-fluorophenyl)butyl]-3-bromo-N-methyl-5-(trifluoromethyl)benzamide

HRID 426077
ノート
印刷プレビュー

反応式

HRID 426077 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[C:5]([N:7]([CH2:9][C@H:10]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:11][CH:12]=O)[CH3:8])=[O:6].[NH:28]1[CH2:31][CH:30]([N:32]2[CH2:37][CH2:36][CH:35]([C:38]([N:40]3[CH2:43][CH2:42][CH2:41]3)=[O:39])[CH2:34][CH2:33]2)[CH2:29]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[N:40]1([C:38]([CH:35]2[CH2:36][CH2:37][N:32]([CH:30]3[CH2:29][N:28]([CH2:12][CH2:11][C@@H:10]([C:14]4[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=4)[CH2:9][N:7]([CH3:8])[C:5](=[O:6])[C:4]4[CH:21]=[C:22]([C:24]([F:26])([F:27])[F:25])[CH:23]=[C:2]([Br:1])[CH:3]=4)[CH2:31]3)[CH2:33][CH2:34]2)=[O:39])[CH2:41][CH2:42][CH2:43]1
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 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 159506583-bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamideHCID 236587781-Azetidin-3-yl-4-(azetidin-1-ylcarbonyl)piperidine

生成物 1

HCID 23582759N-[(2S)-4-{3-[4-(Azetidin-1-ylcarbonyl)piperidin-1-yl]azetidin-1-yl}-2-(4-fluorophenyl)butyl]-3-bromo-N-methyl-5-(trifluoromethyl)benzamide
収率 59.5%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

3-Bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide (see method 1; 0.16 g, 0.36 mmol) and 1-azetidin-3-yl-4-(azetidin-1-ylcarbonyl)piperidine (see method 2; 0.10 g, 0.47 mmol) were dissolved in methylene chloride (10 mL) together with a small amount of dry methanol (0.2 mL). To the resultant solution were added DIPEA (0.14 g, 1.08 mmol) and sodium triacetoxyborohydride (0.15 g, 0.72 mmol). The mixture was stirred under nitrogen for 4 h at RT. The mixture was diluted with methylene chloride and washed twice with saturated aqueous NaHCO3 and then with brine. The organic phase was filtered through a phase separator and the solvent was removed by evaporation. The product was purified by chromatography on silica gel (methanol-methylene chloride, 10:1). There was obtained 0.14 g (59%) of the title compound as a white foam. 1H NMR (500 MHz, CDCl3): δ 1.4-1.8 (cm, 6H), 2.1 (m, 1H) 2.2 (qn, 2H), 2.3-2.4 (cm, 2H), 2.5-3.5 (cm, 14H), 3.6 (d, 1H), 3.9 (t, 2H), 4.1 (t, 2H), 6.8-7.4 (cm, 6H), 7.7 (s, 1H); LCMS: m/z 654 (M+1)+.

後処理

  1. washwashed twice with saturated aqueous NaHCO3
  2. filtrationThe organic phase was filtered through a phase separator
  3. customthe solvent was removed by evaporation
  4. customThe product was purified by chromatography on silica gel (methanol-methylene chloride, 10:1)

出典と根拠

ORDレコード
ord-36a02cae85d54ad9bc3cf9d666967ab1
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08106208B2

反応ノート

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