p-Toluenesulfonic acid → 1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-2-bromo-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 633396노트

반응식

HRID 633396 반응식
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:17][C@H:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[C:11]([CH3:19])([CH3:18])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:32][C:33]1[C:34]([F:47])=[CH:35][C:36]([Br:46])=[C:37]([N:39]2[C:43](=[O:44])[N:42]([CH3:45])[N:41]=[N:40]2)[CH:38]=1.C(=O)(O)[O-].[Na+]>C(O)(C)C>[CH3:18][C:11]1([CH3:19])[CH2:10][C@H:9]([NH:8][C:6]2[C:5]([F:20])=[CH:4][N:3]=[C:2]([NH:32][C:33]3[C:34]([F:47])=[CH:35][C:36]([Br:46])=[C:37]([N:39]4[C:43](=[O:44])[N:42]([CH3:45])[N:41]=[N:40]4)[CH:38]=3)[N:7]=2)[CH2:17][C@H:16]2[N:12]1[CH2:13][CH2:14][CH2:15]2

참가 물질

6

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 86704490(7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-5,5-dimethyloctahydroindolizin-7-amineHCID 867044951-(5-amino-2-bromo-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one

생성물 1

HCID 867044941-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-2-bromo-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one수율 53%

시약·촉매·용매 1

HCID 3776Isopropanol용매

반응 조건

온도
110 °C

실험 절차

(7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (1.4525 g. 4.86 mmol) and p-toluenesulfonic acid (1.7288 g, 9.09 mmol) were weighed out and added to a large reaction tube containing 1-(5-amino-2-bromo-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one (2.10 g, 7.29 mmol). 42 mL isopropyl alcohol was added, and the tube was sealed and heated overnight at 110° C. The reaction was basified with saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The combined organic layer was washed with brine and dried over sodium sulfate. Product solution was filtered, concentrated onto a plug of silica, and purified by column chromatography. Pure fractions were combined, concentrated and dried under high vacuum to give 1.4063 g of the title compound (53% yield).

후처리

  1. additionadded to a large reaction tube
  2. customthe tube was sealed
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationProduct solution was filtered
  7. concentrationconcentrated onto a plug of silica
  8. custompurified by column chromatography
  9. concentrationconcentrated
  10. customdried under high vacuum

출처 및 근거

ORD 기록
ord-bf1cc5c7b62242e0bc028f725756891d
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321763B2

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