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

HRID 272985ノート

反応式

HRID 272985 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 284Formic Acid溶媒

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-d1caacb71b36421fb5f62a84cc0daa22
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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