Diisopropylethylamine → (S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate

HRID 408010

반응식

HRID 408010 반응식
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:14]1=[O:24].C(N(C(C)C)C(C)C)C.[Cl:34][C:35]1[C:36](Cl)=[N:37][CH:38]=[C:39]([CH:44]=1)[C:40]([O:42][CH3:43])=[O:41]>CN(C=O)C.CCOC(C)=O>[Cl:34][C:35]1[C:36]([N:21]2[CH2:22][CH2:23][CH:18]([N:15]3[CH2:16][CH2:17][C@H:13]([NH:12][C:3]4[CH:4]=[CH:5][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:7][C:2]=4[F:1])[C:14]3=[O:24])[CH2:19][CH2:20]2)=[N:37][CH:38]=[C:39]([CH:44]=1)[C:40]([O:42][CH3:43])=[O:41]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 2782166Methyl 5,6-DichloronicotinateHCID 66800375(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

생성물 1

HCID 67469943(S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate수율 47.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 1.0 g, 2.8 mmol) in DMF (30 mL) was added N-ethyl-N-isopropylpropan-2-amine (1.1 g, 8.4 mmol) and methyl 5,6-dichloronicotinate (1.7 g, 8.4 mmol) and the reaction was stirred overnight at ambient temperature. The reaction was diluted with EtOAc (250 mL) and washed with water (100 mL), and brine (50 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum. The crude material was purified on silica using a gradient of 1:9 to 1:4 EtOAc:DCM as eluent to yield a solid, which was further precipitated from using isopropanol to give (S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate (0.70 g, 47% yield).

후처리

  1. washwashed with water (100 mL), and brine (50 mL)
  2. dry with materialthe combined organic phases were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified on silica using a gradient of 1:9 to 1:4 EtOAc
  6. customDCM as eluent to yield a solid, which
  7. customwas further precipitated

출처 및 근거

ORD 기록
ord-7c08e89d10bb488e89b659b4210609b0
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754226B2

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