Trifluoroacetic acid → 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898640노트

반응식

HRID 1898640 반응식
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([Br:24])[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O>ClCCl>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([Br:24])[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2]

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 58438590HCID 58438590, 화합물

생성물 1

HCID 866578762-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (0.104 g, 0.195 mmol, contains some 2-chloro impurity), 1 mL of dichloromethane and 1 mL of TFA was stirred for 3 h, then concentrated to a pale yellow oil. The oil was dissolved in 0.5 mL of dichloromethane and 0.5 mL of ethylene diamine, and the yellow solution was stirred for 1.25 h, then partitioned between 5 mL of water and 10 mL of ethyl acetate. The aqueous layer was extracted with 10 mL of ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated to give 0.087 g of 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a pale yellow residue, which was used without further purification. MS: (M+Na)+=427. A major impurity is 2-chloro-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide. MS: (M+Na)+=381. Approximate 3:1 ratio of Br:Cl.

후처리

  1. concentrationconcentrated to a pale yellow oil
  2. dissolutionThe oil was dissolved in 0.5 mL of dichloromethane
  3. stirring0.5 mL of ethylene diamine, and the yellow solution was stirred for 1.25 h
  4. custompartitioned between 5 mL of water and 10 mL of ethyl acetate
  5. extractionThe aqueous layer was extracted with 10 mL of ethyl acetate
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-4f14942c2690493eb618f887b61ceb8b
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518945B2

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