Diisopropylethylamine → N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 77581

반응식

HRID 77581 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]23[CH2:16][NH:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1.[F:26][C:27]1[CH:28]=[N:29][C:30](Cl)=[N:31][CH:32]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1.O>[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]23[CH2:16][N:15]([C:30]4[N:31]=[CH:32][C:27]([F:26])=[CH:28][N:29]=4)[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:25])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 5834662-Chloro-5-fluoropyrimidineHCID 86762765N-[(4aR,7aS)-7a-(3-Aminophenyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

생성물 1

HCID 86762768N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide수율 79.3%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

A solution of N-[(4aR,7aS)-7a-(3-aminophenyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (2.49 g, 7.06 mmol), 5-fluoro-2-chloropyrimidine (3.74 g, 28.26 mmol), and diisopropylethylamine (6.16 mL, 35.32 mmol) in 1,4-dioxane (60 mL) is heated to reflux for 4 hours under nitrogen. The reaction is cooled, diluted with water and extracted with ethyl acetate (3×). The combined organic extracts are dried over sodium sulfate, filtered and the solvent is removed in vacuo to give the crude product. The crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient to give the title compound (2.51 g, 79%). ES/MS (m/e): 449 (M+H).

후처리

  1. temperatureto reflux for 4 hours under nitrogen
  2. temperatureThe reaction is cooled
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organic extracts are dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent is removed in vacuo
  7. customto give the crude product
  8. customThe crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient

출처 및 근거

ORD 기록
ord-66ea0de20f9a4ae38c13d32f501816e4
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841293B1

연결된 노트

불러오는 중…