Ethyl Acetate → (S)-2-[(2-Carbamoyl-2-methyl-propylcarbamoyl)-methyl]-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963072ノート

反応式

HRID 1963072 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[CH:21][CH:22]=[CH:23]3)=[C:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2[CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[CH3:39])=[O:15])[CH2:10][C@@H:9]1[CH2:40][C:41](O)=[O:42])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:44][CH2:45][C:46]([CH3:51])([CH3:50])[C:47]([NH2:49])=[O:48].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CC(=O)OCC>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[CH:21][CH:22]=[CH:23]3)=[C:18]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:17]=2[CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[CH3:39])=[O:15])[CH2:10][C@@H:9]1[CH2:40][C:41](=[O:42])[NH:44][CH2:45][C:46]([C:47](=[O:48])[NH2:49])([CH3:51])[CH3:50])=[O:7])([CH3:3])([CH3:4])[CH3:2]

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 111593153-Amino-2,2-dimethylpropanamideHCID 70663959{(S)-1-tert-Butoxycarbonyl-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazin-2-yl}-acetic acid

生成物 1

HCID 67773127(S)-2-[(2-Carbamoyl-2-methyl-propylcarbamoyl)-methyl]-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester収率 91.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

The compound of step 5 (0.176 g, 0.30 mmol) was dissolved in 2.5 ml of anhydrous DCM at 0° C. 3-Amino-2,2-dimethyl-propionamide (0.044 g, 0.38 mmol), EDIA (0.13 ml, 0.75 mmol) and TBTU (0.120 g, 0.38 mmol) were added and the solution was stirred at room temperature for 60 h. EA (15 ml) was then added and the solution was washed with water, 1 N hydrochloric acid, a saturated solution of sodium hydrogencarbonate and brine. The organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (EA/MOH, 100:0, then 97:5, then 95:5) to give 0.188 g of the title compound as a greenish-brown wax.

後処理

  1. washthe solution was washed with water, 1 N hydrochloric acid
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (EA/MOH, 100:0

出典と根拠

ORDレコード
ord-efc0894f6a164684aa8ce60793ac228b
出典データセット
uspto-grants-2013_04
特許番号
US08415336B2

反応ノート

読み込み中…