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 1951667ノート

反応式

HRID 1951667 の反応式
[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]

参加物

6

反応物 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

生成物 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-isobutyramide収率 59.8%

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
130 °C

実験手順

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. MS m/e (%): 657 (M+H+)

後処理

  1. temperatureAfter cooling to room temperature

出典と根拠

ORDレコード
ord-38b4d344a001477ba6032d7420481ea4
出典データセット
uspto-grants-2013_03
特許番号
US08404708B2

反応ノート

読み込み中…