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 547759Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 130 °C

Procedure

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.

Workup

temperatureAfter cooling to room temperature

Sources & evidence

ORD record: ord-e224e0c37eda410d90aabd28c207b00a
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07939533B2

Reaction notes

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