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

HRID 1796219ノート

反応式

HRID 1796219 の反応式
[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: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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒2 回

反応条件

温度
0 °C

実験手順

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, cooled in an ice water bath, added dry pyridine (3 mL, 37.2 mmol) followed by the dropwise addition of oxalyl chloride (1.6 mL, 18.6 mmol). A precipitate forms immediately. The reaction was stirred vigorously at 0° C. for one hour, then at ambient temperature for one hour. Added 50 mL diethyl ether, filtered off solids washing with diethyl ether. Concentrated the filtrates to an off-white oil. Redissolved oil in 40 mL dry DCM under Ar, cooled to 0° C., added 3 mL pyridine 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. 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. 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)−.

後処理

  1. temperaturecooled in an ice water bath
  2. waitat ambient temperature for one hour
  3. filtrationfiltered off solids
  4. washwashing with diethyl ether
  5. concentrationConcentrated the filtrates to an off-white oil
  6. dissolutionRedissolved oil in 40 mL dry DCM under Ar
  7. temperaturecooled to 0° C.
  8. additionadded 3 mL pyridine
  9. temperatureto warm to ambient temperature
  10. stirringstirred for 3 hours
  11. concentrationthen concentrated
  12. dissolutionRedissolved in 250 mL EtOAc
  13. washwashed with 10% citric acid (2×100 mL), water (3×100 mL), brine (100 mL)
  14. dry with materialdried with MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurified on a silica gel column
  18. washeluted with 30%
  19. concentrationconcentrated pure fractions

出典と根拠

ORDレコード
ord-33283ac476ce46be96f40f057c0cbb20
出典データセット
uspto-grants-2006_04
特許番号
US07030141B2

反応ノート

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