Potassium Carbonate → 1-(4-Bromo-2-methylphenyl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

HRID 1398990ノート

反応式

HRID 1398990 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:13]([CH2:14][CH2:15][CH2:16][CH2:17]O)[C:12]3[C:19]([CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[CH:20][CH:21]=[C:22]([Cl:23])[C:11]=3[N:10]=2)=[C:4]([CH3:29])[CH:3]=1.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(N(CC)CC)C.C(=O)([O-])O.[Na+].CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9]3=[N:10][C:11]4[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]([CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])[C:12]=4[N:13]3[CH2:14][CH2:15][CH2:16][CH2:17]2)=[C:4]([CH3:29])[CH:3]=1

参加物

10

反応物 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 68765623HCID 68765623、化合物

生成物 1

HCID 577863541-(4-Bromo-2-methylphenyl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

試薬・触媒・溶媒 5

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
0 °C

実験手順

To a solution of 4-[2-[(4-bromo-2-methylphenyl)amino]-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol (Reference Example 61; 1.10 g, 2.30 mmol) in tetrahydrofuran (20 mL) and triethylamine (1.6 mL) was added methanesulfonyl chloride (0.72 mL, 9.24 mmol) at 0° C. The mixture was stirred at 0° C. for 14 hr, and diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. A mixture of the resulting mesylate, potassium carbonate (150 mg, 1.09 mmol) in N,N-dimethylformamide (15 mL) was stirred at 70° C. for 3 hr. The mixture was diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 0-30 % ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was purified by preparative HPLC to give a mixture contained the title compound as the trifluoroacetic acid salt. The trifluoroacetic acid salt was washed with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the title compound as a colorless amorphous (680 mg, 1.48 mmol, 64% in 2 steps).

後処理

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringwas stirred at 70° C. for 3 hr
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layer was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash column chromatography on silica gel eluting with a 0-30 % ethyl acetate/n-hexane gradient mixture
  13. concentrationThe filtrate was concentrated in vacuo
  14. customto give the solid, which
  15. customwas purified by preparative HPLC
  16. customto give a mixture

出典と根拠

ORDレコード
ord-a9628f1ac7ff4ebf971419817405b09d
出典データセット
uspto-grants-2014_12
特許番号
US08901141B2

反応ノート

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