O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → (S)-4-[2-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-{[(tetrahydropyran-4-ylmethyl)-carbamoyl]-methyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963065노트

반응식

HRID 1963065 반응식
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([C:24]2[N:32]3[C:27]([CH:28]=[CH:29][CH:30]=[CH:31]3)=[C:26]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:25]=2[CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:41]=2[CH3:47])=[O:23])[CH2:18][C@@H:17]1[CH2:48][C:49](O)=[O:50])=[O:15])([CH3:12])([CH3:11])[CH3:10].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([C:24]2[N:32]3[C:27]([CH:28]=[CH:29][CH:30]=[CH:31]3)=[C:26]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:25]=2[CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:41]=2[CH3:47])=[O:23])[CH2:18][C@@H:17]1[CH2:48][C:49](=[O:50])[NH:1][CH2:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1)=[O:15])([CH3:11])([CH3:12])[CH3:10]

참가 물질

5

반응물 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27732104-AminomethyltetrahydropyranHCID 70663959{(S)-1-tert-Butoxycarbonyl-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazin-2-yl}-acetic acid

생성물 1

HCID 70663881(S)-4-[2-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-{[(tetrahydropyran-4-ylmethyl)-carbamoyl]-methyl}-piperazine-1-carboxylic acid tert-butyl ester수율 63.5%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

To a stirred, ice-cold solution of 4-aminomethyl-tetrahydropyran (0.047 g, 0.40 mmol), EDIA (0.19 ml, 1.08 mmol) and the compound of step 2 (0.190 g, 0.27 mmol) was added TBTU (0.259 g, 0.81 mmol) in small portions. The solution was stirred at room temperature for 18 h. Then water (8 ml) was added and the mixture was extracted 3 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 (cyclohexane/EA, 100:0, then 50:50) to give 0.117 g of the title compound as an orange gum.

후처리

  1. extractionthe mixture was extracted 3 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 (cyclohexane/EA, 100:0

출처 및 근거

ORD 기록
ord-1b68f16768c74f6b8102b3113961876c
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415336B2

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