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

HRID 1747164노트

반응식

HRID 1747164 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-63dcca66cec549d6baf1731740316cb5
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150550B2

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