Pyridine → 2-(2'-tert-Butylsulfamoyl-3-fluoro-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1796214노트

반응식

HRID 1796214 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[C:28]([NH:32][S:33]([C:36]1[C:37]([C:42]2[CH:47]=[CH:46][C:45]([NH2:48])=[C:44]([F:49])[CH:43]=2)=[CH:38][CH:39]=[CH:40][CH:41]=1)(=[O:35])=[O:34])([CH3:31])([CH3:30])[CH3:29]>C(OCC)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:15])[NH:48][C:45]1[CH:46]=[CH:47][C:42]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[S:33](=[O:35])(=[O:34])[NH:32][C:28]([CH3:29])([CH3:30])[CH3:31])=[CH:43][C:44]=1[F:49])=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 4

HCID 1049Pyridine2회HCID 65578Oxalyl chlorideHCID 2684721-[(Tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 108532844'-Amino-3'-fluoro-biphenyl-2-sulfonic acid tert-butylamide

생성물 1

HCID 688068732-(2'-tert-Butylsulfamoyl-3-fluoro-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 3283Diethyl Ether용매2회HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.6 g, 7.4 mmol) was dissolved in 40 mL dry diethyl ether under Ar. The solution was cooled in an ice water bath as dry pyridine (3 mL, 37.2 mmol) was added, followed by the dropwise addition of oxalyl chloride (1.6 mL, 18.6 mmol). A precipitate formed immediately. The reaction was stirred vigorously at 0° C. for one hour, then at ambient temperature for one hour. 50 mL diethyl ether were added, and the mixture was filtered. The filtered off solids were washed with diethyl ether. The filtrates were combined and concentrated to give an off-white oil. The oil was redissolved in 40 mL dry DCM under Ar, cooled to 0° C., and 3 mL of pyridine were added, followed by 4′-amino-3′-fluoro-biphenyl-2-sulfonic acid tert-butylamide (2 g, 6.2 mmol). The reaction was allowed to warm to ambient temperature, stirred for 3 hours then concentrated. The concentrate was redissolved in 250 mL EtOAc, washed with 10% citric acid (2×100 mL), water (3×100 mL), brine (100 mL), dried with MgSO4, filtered and concentrated. The concentrate was purified on a silica gel column eluted with 30% moving to 50% EtOAc in hexanes. Combined and concentrated pure fractions to yield title compound as a white solid. (1.4 g, 42%) APCI (AP−): 518.2 (M−H)−.

후처리

  1. additionwas added
  2. customA precipitate formed immediately
  3. waitat ambient temperature for one hour
  4. filtrationthe mixture was filtered
  5. filtrationThe filtered off solids
  6. washwere washed with diethyl ether
  7. concentrationconcentrated
  8. customto give an off-white oil
  9. temperaturecooled to 0° C.
  10. temperatureto warm to ambient temperature
  11. stirringstirred for 3 hours
  12. concentrationthen concentrated
  13. dissolutionThe concentrate was redissolved in 250 mL EtOAc
  14. washwashed with 10% citric acid (2×100 mL), water (3×100 mL), brine (100 mL)
  15. dry with materialdried with MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customThe concentrate was purified on a silica gel column
  19. washeluted with 30%
  20. concentrationconcentrated pure fractions

출처 및 근거

ORD 기록
ord-127fcfa81e33473790da7c0d0fbe2107
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07030141B2

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