1,2-Dimethoxyethane → [1-(2-{5-[4'-(2-tert-butoxycarbonylamino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 71747ノート

反応式

HRID 71747 の反応式
[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1)=[O:10])([CH3:4])([CH3:3])[CH3:2].[CH3:19][O:20][C:21](=[O:54])[NH:22][CH:23]([C:27]([N:29]1[CH2:33][CH2:32][CH2:31][CH:30]1[C:34]1[NH:35][C:36]([C:39]2[CH:44]=[CH:43][C:42](B3OC(C)(C)C(C)(C)O3)=[CH:41][CH:40]=2)=[CH:37][N:38]=1)=[O:28])[CH:24]([CH3:26])[CH3:25].C(=O)([O-])[O-].[K+].[K+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:19][O:20][C:21](=[O:54])[NH:22][CH:23]([C:27]([N:29]1[CH2:33][CH2:32][CH2:31][CH:30]1[C:34]1[NH:35][C:36]([C:39]2[CH:40]=[CH:41][C:42]([C:14]3[CH:15]=[CH:16][C:11]([C:9](=[O:10])[CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:18])=[CH:12][CH:13]=3)=[CH:43][CH:44]=2)=[CH:37][N:38]=1)=[O:28])[CH:24]([CH3:26])[CH3:25]

参加物

7

反応物 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 59610197tert-butyl N-[2-(4-bromophenyl)-2-oxoethyl]carbamateHCID 66619939[2-Methyl-1-(2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester

生成物 1

HCID 66620939[1-(2-{5-[4'-(2-tert-butoxycarbonylamino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester収率 44%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

A mixture of [2-(4-Bromo-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester (1 g, 3.2 mmol), [2-methyl-1-(2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (1.57 g, 3.2 mmol), tetrakis(triphenylphosphine)palladium(0) (183 mg, 0.15 mmol), potassium carbonate (878 mg, 6.5 mmol), 1,2-dimethoxyethane (25 mL) and water (2.5 mL) was stirred at 80° C. for 16 hours. The mixture was cooled and all volatiles were removed under reduced pressure. The resulting residue was taken up in dichloromethane (100 mL) and washed with water (25 mL) and saturated sodium chloride (25 mL). The organic phase was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to provide [1-(2-{5-[4′-(2-tert-butoxycarbonylamino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (869 mg, 1.4 mmol, 44%).

後処理

  1. temperatureThe mixture was cooled
  2. customall volatiles were removed under reduced pressure
  3. washwashed with water (25 mL) and saturated sodium chloride (25 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was removed under reduced pressure
  7. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-fa267a6c2f1445a183149ac2c6c14be3
出典データセット
uspto-grants-2014_09
特許番号
US08822430B2

反応ノート

読み込み中…