Isopropyl Acetate → (2S,4R)-1-(2-Isopropyl-5-methyl-2H-pyrazol-3-yl)-4-[4-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-benzenesulfonyl]-pyrrolidine-2-carboxylic Acid Methyl Ester

HRID 1697597

반응식

HRID 1697597 반응식
COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1.Cl.[CH:24]([NH:27][NH2:28])([CH3:26])[CH3:25].[CH3:29][O:30][C:31]([C@@H:33]1[CH2:37][C@@H:36]([S:38]([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][C:49]([F:52])([F:51])[F:50])=[CH:43][C:42]=2[C:53]([F:56])([F:55])[F:54])(=[O:40])=[O:39])[CH2:35][N:34]1[C:57](=O)[CH2:58][C:59](=O)[CH3:60])=[O:32].COC([C@@H]1C[C@@H](S(C2C=CC(F)=CC=2C(F)(F)F)(=O)=O)CN1C(=O)CC(=O)C)=O.C(OC(C)=O)(C)C.COC([C@@H]1C[C@@H](S(C2C=CC(F)=CC=2C(F)(F)F)(=O)=O)CN1C1N(C(C)C)N=C(C)C=1)=O>O1CCCC1.N1C=CC=CC=1>[CH3:29][O:30][C:31]([C@@H:33]1[CH2:37][C@@H:36]([S:38]([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][C:49]([F:50])([F:51])[F:52])=[CH:43][C:42]=2[C:53]([F:55])([F:56])[F:54])(=[O:40])=[O:39])[CH2:35][N:34]1[C:57]1[N:27]([CH:24]([CH3:26])[CH3:25])[N:28]=[C:59]([CH3:60])[CH:58]=1)=[O:32]

참가 물질

9

반응물 6

HCID 7915Isopropyl AcetateHCID 855731-Isopropylhydrazine hydrochlorideHCID 87949Lawesson's reagentHCID 67278474(2S,4R)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-1-(2-isopropyl-5-methyl-2H-pyrazol-3-yl)-pyrrolidine-2-carboxylic acid methyl esterHCID 86646828(2S,4R)-4-(4-Fluoro-2-trifluoromethyl-benzenesulfonyl)-1-(3-oxo-butyryl)-pyrrolidine-2-carboxylic Acid Methyl EsterHCID 86646840(2S,4R)-1-(3-oxo-butyryl)-4-[4-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-benzenesulfonyl]-pyrrolidine-2-carboxylic acid methyl ester

생성물 1

HCID 86646839(2S,4R)-1-(2-Isopropyl-5-methyl-2H-pyrazol-3-yl)-4-[4-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-benzenesulfonyl]-pyrrolidine-2-carboxylic Acid Methyl Ester

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
55 °C

실험 절차

Lawesson's reagent (39 mg, 106 umol; CAS Reg. No. 19172-47-5) and isopropylhydrazine hydrochloride (12 mg, 106 umol; CAS Reg. No. 16726-41-3) were added to a solution of (2S,4R)-1-(3-oxo-butyryl)-4-[4-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-benzenesulfonyl]-pyrrolidine-2-carboxylic acid methyl ester and (2S,4R)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-1-(3-oxo-butyryl)-pyrrolidine-2-carboxylic acid methyl ester (50 mg, 96 umol) in tetrahydrofuran (2.9 ml) and pyridine (0.1 ml) under an argon atmosphere. The mixture was stirred for 16 h at 55° C. and for additional 48 h at ambient temperature. Ice water/0.1 N aqueous HCl solution 1/1 and iPrOAc were added and the layers were separated. The aqueous layer was extracted one more time with iPrOAc, the combined organic layers were washed with ice water/10% aqueous sodium carbonate solution, ice water/brine 1/1 and dried over Na2SO4. The solvent was removed under reduced pressure to give a yellow oil which was purified by preparative thin layer chromatography (silica gel, iPrOAc/heptane) to obtain a mixture of the title compound and (2S,4R)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-1-(2-isopropyl-5-methyl-2H-pyrazol-3-yl)-pyrrolidine-2-carboxylic acid methyl ester (39 mg, 70 umol; 73%) as colorless oil. MS (ESI): m/z=558.2 [M+H]+.

후처리

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted one more time with iPrOAc
  3. washthe combined organic layers were washed with ice water/10% aqueous sodium carbonate solution, ice water/brine 1/1
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed under reduced pressure
  6. customto give a yellow oil which
  7. customwas purified by preparative thin layer chromatography (silica gel, iPrOAc/heptane)
  8. customto obtain

출처 및 근거

ORD 기록
ord-779d49181e9846cf84c46867d735c589
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163793B2

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