Dimethylformamide → 6-Cyano-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 2076177노트

반응식

HRID 2076177 반응식
[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([F:10])[C:7](Cl)=[N:6][C:5]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][C:14]=1[F:23].[CH3:25][N:26](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([C:25]#[N:26])=[N:6][C:5]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][C:14]=1[F:23]

참가 물질

5

반응물 2

HCID 6228DimethylformamideHCID 591401696-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

생성물 1

HCID 591401176-Cyano-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester수율 91%

시약·촉매·용매 2

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 178418397HCID 178418397, 화합물촉매

실험 절차

A degassed suspension of 6-chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (7.8 g, 21.2 mmol), zinc (II) cyanide (1.84 g, 15.6 mmol), and Pd(PPh3)4 (2.43 g, 2.12 mmol) in DMF (40 mL) was subjected to microwave irradiation at 150° C. for 15 minutes. The reaction mixture was filtered through Celite® and the filtrate diluted with ethyl acetate. The organic phase was washed twice with water and once with brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was triturated with diethyl ether and pentane, and then dried under vacuum to afford the title compound as a yellow solid (6.9 g, 91%). LCMS (method B): RT=4.99 min, [M+H]+=362.

후처리

  1. customirradiation at 150° C. for 15 minutes
  2. filtrationThe reaction mixture was filtered through Celite®
  3. additionthe filtrate diluted with ethyl acetate
  4. washThe organic phase was washed twice with water and once with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was triturated with diethyl ether and pentane
  9. customdried under vacuum

출처 및 근거

ORD 기록
ord-ebd573e8fdfb43e7867848199aa6eeca
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07923456B2

반응 노트

불러오는 중…