Trimethyl orthoformate → 2-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1H-benzimidazole

HRID 272985노트

반응식

HRID 272985 반응식
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH:23][C:24]4[C:25]([NH2:30])=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.COC(OC)OC>C(O)=O>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3([C:22]4[NH:30][C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=5[N:23]=4)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:14][CH:15]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

4

반응물 2

HCID 9005Trimethyl orthoformateHCID 68576071N-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)benzene-1,2-diamine

생성물 1

HCID 598373462-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1H-benzimidazole수율 30.3%

시약·촉매·용매 1

HCID 284Formic Acid용매

실험 절차

N-({4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)benzene-1,2-diamine (500 mg, 1.22 mmol), trimethylorthoformate (5 ml) and formic acid (0.5 ml) were stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between aqueous sodium carbonate (50 ml) and ethyl acetate (100 ml). The layers were separated and the organic phase washed with water (50 ml), dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:0.2 to 92:8:1 by volume). The relevant fractions were evaporated and the residue taken up in diethyl ether (20 ml). The unsoluble material was filtered off and the filtrate concentrated in vacuo to provide the title compound (150 mg, 29%). 1H NMR (400 MHz, CD3OD) δ 1.83-1.85 (m, 4H), 1.98-2.06 (m, 4H), 2.23 (d, 2H), 2.62 (s, 4H), 2.69 (t, 2H), 3.42 (t, 2H), 3.82 (d, 2H), 4.00 (t, 2H), 4.33 (s, 2H), 6.84 (d, 2H), 7.06 (d, 2H), 7.14-7.18 (m, 3H), 7.26 (s, 1H), 7.55 (d, 1H). HRMS ESI+ m/z 420.2637 [MH]+.

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between aqueous sodium carbonate (50 ml) and ethyl acetate (100 ml)
  3. customThe layers were separated
  4. washthe organic phase washed with water (50 ml)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:0.2 to 92:8:1 by volume)
  9. customThe relevant fractions were evaporated
  10. filtrationThe unsoluble material was filtered off
  11. concentrationthe filtrate concentrated in vacuo

출처 및 근거

ORD 기록
ord-d1caacb71b36421fb5f62a84cc0daa22
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07456164B2

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