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

HRID 408010

反応式

HRID 408010 の反応式
[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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7c08e89d10bb488e89b659b4210609b0
出典データセット
uspto-grants-2014_06
特許番号
US08754226B2

関連ノート

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