Triethylamine → 4-[2-(3-Fluoro-2-methyl-benzyl)-7-methylcarbamoyl-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963058ノート

反応式

HRID 1963058 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]=[C:21]([C:25]([OH:27])=O)[CH:22]=[CH:23]3)=[C:18]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:17]=2[CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=2[CH3:42])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN.[CH2:46]([N:48](CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[C:21]([C:25](=[O:27])[NH:48][CH3:46])[CH:22]=[CH:23]3)=[C:18]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:17]=2[CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=2[CH3:42])=[O:15])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6364545Methylamine hydrochlorideHCID 677727443-(4-tert-Butoxycarbonyl-piperazine-1-carbonyl)-2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-7-carboxylic acid

生成物 1

HCID 677721744-[2-(3-Fluoro-2-methyl-benzyl)-7-methylcarbamoyl-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester収率 46.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

The compound of step 6 (0.139 g, 0.24 mmol), methylamine hydrochloride (0.022 g, 0.32 mmol) and triethylamine (0.17 ml, 0.97 mmol) were dissolved in 2 ml of DMF and cooled to 0° C. TBTU (0.195 g, 0.61 mmol) was added and the solution was stirred at room temperature overnight. Water (8 ml) was then added and the mixture was extracted three times with EA. The combined organic phases were washed with 1 N hydrochloric acid, water, a saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (DCM/MOH, 100:0, then 96:4) to give 0.065 g of the title compound as a beige solid.

後処理

  1. extractionthe mixture was extracted three times with EA
  2. washThe combined organic phases were washed with 1 N hydrochloric acid, water
  3. dry with materiala saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (DCM/MOH, 100:0

出典と根拠

ORDレコード
ord-dff2dff6aa0943cf80e30770ba73a4c0
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…