Dimethyl Sulfoxide → (2S,4S)-N-[6-(4-Acetylamino-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-chloro-phenyl)-pyridin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-isobutyramide

HRID 547759노트

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HRID 547759 반응식
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]([CH3:33])([CH3:32])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Cl:30])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:36]([NH:39][C@@H:40]1[CH2:44][NH:43][C@H:42]([CH2:45][OH:46])[CH2:41]1)(=[O:38])[CH3:37].CS(C)=O.CC#N>C(O)(C(F)(F)F)=O>[C:36]([NH:39][C@@H:40]1[CH2:44][N:43]([C:21]2[N:20]=[CH:19][C:18]([N:16]([CH3:17])[C:14](=[O:15])[C:13]([C:5]3[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=[C:3]([C:2]([F:34])([F:1])[F:35])[CH:4]=3)([CH3:33])[CH3:32])=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[Cl:30])[CH:22]=2)[C@H:42]([CH2:45][OH:46])[CH2:41]1)(=[O:38])[CH3:37]

참가 물질

6

반응물 4

HCID 679Dimethyl SulfoxideHCID 6342AcetonitrileHCID 235028372-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(2-chlorophenyl)-3-pyridinyl]-N,2-dimethylpropanamideHCID 67196537(2S,4S)-4-acetylamino-2-hydroxymethyl-pyrrolidine

생성물 1

HCID 86597670(2S,4S)-N-[6-(4-Acetylamino-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-chloro-phenyl)-pyridin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-isobutyramide수율 59.8%

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

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온도
130 °C

실험 절차

A mixture of 30 mg (0.056 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-chloro-4-(2-chloro-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide, 200 mg (1.27 mmol) (2S,4S)-4-acetylamino-2-hydroxymethyl-pyrrolidine and 0.2 ml dimethyl sulfoxide was heated at 130° C. for 24 h. After cooling to room temperature, 22 mg (59%) of the title compound were isolated as a white solid by automated, preparative HPLC (YMC CombiPrep C18 column 50×20 mm, solvent gradient 5-95% CH3CN in 0.1% TFA(aq) over 6.0 min, λ=230 nm, flow rate 40 ml/min). (2S,4S)-4-Acetylamino-2-hydroxymethyl-pyrrolidine can be obtained by the method described by Terry Rosen, Daniel T. W. Chu, Isabella M. Lico, Isabella M. Lico, Prabhavathi B. Fernandes, Kennan Marsh, Linus Shen, Valerie G. Cepa, André G. Pernet, J. Med. Chem. 1988, 31, 1598.

후처리

  1. temperatureAfter cooling to room temperature

출처 및 근거

ORD 기록
ord-e224e0c37eda410d90aabd28c207b00a
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07939533B2

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