1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide

HRID 19370노트

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HRID 19370 반응식
[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH2:15][O:16][CH3:17])[C:11]([OH:13])=O)[C:7](=[O:18])[CH:6]=1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH3:44][C:45]1([CH3:57])[O:49][C@H:48]([CH2:50][N:51]2[CH:55]=[CH:54][C:53]([NH2:56])=[N:52]2)[CH2:47][O:46]1>ClCCl>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH2:15][O:16][CH3:17])[C:11]([NH:56][C:53]2[CH:54]=[CH:55][N:51]([CH2:50][C@@H:48]3[CH2:47][O:46][C:45]([CH3:57])([CH3:44])[O:49]3)[N:52]=2)=[O:13])[C:7](=[O:18])[CH:6]=1

참가 물질

6

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 66895181HCID 66895181, 화합물

생성물 1

HCID 67504039(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide수율 27.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
25 °C

실험 절차

In a round bottom flask under argon was placed (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methoxy-butyric acid (62 mg, 0.19 mmol) in dichloromethane (5 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (37 μL, 0.21 mmol) and 1-hydoxybenzotriazole (27 mg, 0.20 mmol) and stirred at 25° C. for 2 h. After this time period, 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 45 mg, 0.23 mmol) was added and stirred for 16 h at 25° C. After this time, the reaction was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL) and a saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 50% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide (26 mg, 27%) as a colorless oil.

후처리

  1. customIn a round bottom flask under argon was placed
  2. stirringstirred for 16 h at 25° C
  3. washwashed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL)
  4. dry with materiala saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by AnaLogix IntelliFlash flash chromatography (4 g column, 50% ethyl acetate/hexanes to 100% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-16de470a679948329107fd95f1fee2fd
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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