Cyclohexanone → (R)-6-(1-cyclohexyl-1,2,3,6-tetrahydropyridin-4-yl)-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole

HRID 1747164ノート

反応式

HRID 1747164 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C@H:9]([N:11]1[C:15]2[CH:16]=[C:17]([C:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH:25]=3)[CH:18]=[CH:19][C:14]=2[N:13]=[CH:12]1)[CH3:10].[C:26]1(=O)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[CH:26]1([N:23]2[CH2:22][CH:21]=[C:20]([C:17]3[CH:18]=[CH:19][C:14]4[N:13]=[CH:12][N:11]([C@@H:9]([C:3]5[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=5[Cl:1])[CH3:10])[C:15]=4[CH:16]=3)[CH2:25][CH2:24]2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

参加物

6

反応物 3

HCID 7967CyclohexanoneHCID 5049666Sodium triacetoxyborohydrideHCID 86688430(R)-1-(1-(2,4-dichlorophenyl)ethyl)-6-(1,2,3,6-tetrahydropyridin-4-yl)-1H-benzo[d]imidazole

生成物 1

HCID 71581877(R)-6-(1-cyclohexyl-1,2,3,6-tetrahydropyridin-4-yl)-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole収率 25%

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 6344Dichloromethane溶媒

実験手順

To a stirred solution of the crude (R)-1-(1-(2,4-dichlorophenyl)ethyl)-6-(1,2,3,6-tetrahydropyridin-4-yl)-1H-benzo[d]imidazole (prepared from Example 4 step d, 0.047 g, 0.13 mmol) and cyclohexanone (0.0.038 g, 0.38 mmol) in dichloromethane (1 mL) was added sodium triacetoxyborohydride (NaBH(OAc)3, 0.11 g, 0.52 mmol) and acetic acid (3 drops). The reaction mixture was stirred at room temperature for 18 h, and quenched with saturated aqueous sodium bicarbonate. The mixture was extracted with dichloromethane (2×15 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude material was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give a white solid (0.015 g, 0.032 mmol, 25%). 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1 H), 7.69 (d, J=8.4 Hz, 1 H), 7.44 (d, J=2.4 Hz, 1 H), 7.32 (dd, J=1.2, 8.4 Hz, 1 H), 7.12 (dd, J=2.4, 8.4 Hz, 1 H), 7.06 (s, 1 H), 6.82 (d, J=8.4 Hz, 1 H), 5.99-5.94 (m, 2 H), 3.30 (d, J=2.8 Hz, 2 H), 2.81-2.78 (m, 2 H), 2.58-2.48 (m, 2 H), 2.38-2.36 (m, 1 H), 1.97 (d, J=6.8 Hz, 3 H), 1.94-1.82 (m, 4 H), 1.67-1.64 (m, 1 H), 1.31-1.26 (m, 4 H), 1.15-1.11 (m, 1 H); MS: (ES) m/z calculated for C26H30Cl2N3 [M+H]+ 454.2, found 453.

後処理

  1. customquenched with saturated aqueous sodium bicarbonate
  2. extractionThe mixture was extracted with dichloromethane (2×15 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude material was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

出典と根拠

ORDレコード
ord-63dcca66cec549d6baf1731740316cb5
出典データセット
uspto-grants-2015_10
特許番号
US09150550B2

反応ノート

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