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

HRID 1963058노트

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HRID 1963058 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-dff2dff6aa0943cf80e30770ba73a4c0
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415336B2

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