Pyridine → (S)-2-[2-(tert-Butyl-dimethyl-silyloxy)-ethyl]-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963061노트

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HRID 1963061 반응식
[F:1][C:2]1[C:3]([CH3:24])=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][C:6]1[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:8]2[N:13]([CH:14]=1)[CH:12]=[CH:11][CH:10]=[CH:9]2.N1C=CC=CC=1.[C:31](Cl)(Cl)=[O:32].C1(C)C=CC=CC=1.[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][NH:52][CH2:51][C@@H:50]1[CH2:55][CH2:56][O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:60])[CH3:59])=[O:48])([CH3:45])([CH3:44])[CH3:43].C(N(CC)CC)C>C(Cl)Cl>[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][N:52]([C:31]([C:14]2[N:13]3[C:8]([CH:9]=[CH:10][CH:11]=[CH:12]3)=[C:7]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:6]=2[CH2:5][C:4]2[CH:21]=[CH:22][CH:23]=[C:2]([F:1])[C:3]=2[CH3:24])=[O:32])[CH2:51][C@@H:50]1[CH2:55][CH2:56][O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:60])[CH3:59])=[O:48])([CH3:45])([CH3:44])[CH3:43]

참가 물질

8

반응물 6

HCID 1049PyridineHCID 1140TolueneHCID 6371PhosgeneHCID 8471TriethylamineHCID 677730242-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizineHCID 67773623(S)-2-[2-(tert-butyl-dimethyl-silyloxy)-ethyl)-piperazine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 70663954(S)-2-[2-(tert-Butyl-dimethyl-silyloxy)-ethyl]-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

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온도
0 °C

실험 절차

The compound of example 1, step 3 (1.00 g, 3.17 mmol) was dissolved in 15 ml of DCM and cooled to 0° C. To this solution was added pyridine (0.26 ml, 3.17 mmol) and a 20% solution of phosgene in toluene (1.67 ml, 3.17 mmol) and the mixture was stirred for 2.5 h at room temperature. This solution was then added dropwise to a solution of the compound of step 3 (1.202 g, 3.49 mmol) in 25 ml of DCM containing triethylamine (0.44 ml, 3.49 mmol) and the mixture stirred overnight at room temperature. DCM (25 ml) was added and the solution was washed with 25 ml of 0.5 N hydrochloric acid, 25 ml of a saturated solution of sodium hydrogencarbonate and 25 ml of brine. The organic phase was dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane/EA, 85:15, then 80:20) to give 1.33 g of the title compound as an off-white powder melting at 70° C.

후처리

  1. washthe solution was washed with 25 ml of 0.5 N hydrochloric acid, 25 ml of a saturated solution of sodium hydrogencarbonate and 25 ml of brine
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (cyclohexane/EA, 85:15

출처 및 근거

ORD 기록
ord-07135099a88645b8b374f61e2069c562
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415336B2

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