Sulfuric Acid → HCID 59249382, compound

HRID 1807206Notes

Reaction equation

C([O:5][C:6](=[O:44])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([C@H:16]2[C@H:20]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=3[F:28])[C@:19]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[F:38])([C:29]#[N:30])[C@H:18]([CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[NH:17]2)=[O:15])=[N:9]1)(C)(C)C.S(=O)(=O)(O)O>O>[Cl:27][C:23]1[C:22]([F:28])=[C:21]([C@@H:20]2[C@:19]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[F:38])([C:29]#[N:30])[C@H:18]([CH2:39][C:40]([CH3:41])([CH3:42])[CH3:43])[NH:17][C@H:16]2[C:14]([NH:13][C:10]2[CH:11]=[CH:12][N:8]([CH2:7][C:6]([OH:44])=[O:5])[N:9]=2)=[O:15])[CH:26]=[CH:25][CH:24]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of rac-(3-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-pyrazol-1-yl)-acetic acid tert-butyl ester (25 mg, 0.039 mmol) was chilled to 0° C. Then concentrated sulfuric acid (1 mL) was added and the reaction was stirred for 2 hours. Ice and water added all at once, crystals filtered and washed with water. The crystals were azeotroped three times with toluene then treated to high vacuum overnight to yield rac-(3-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-pyrazol-1-yl)-acetic acid as an off white powder (12.1 mg, 53%). HRMS (ES+) m/z Calcd for C28H27Cl2F2N5O3+H [(M+H)+]: 590.1532. found: 590.1531.

Workup

filtrationfiltered
washwashed with water
customThe crystals were azeotroped three times with toluene
additionthen treated to high vacuum overnight

Sources & evidence

ORD record: ord-daa0a9ef30eb4ef891a044c0a1c5735c
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354444B2

Reaction notes

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