Cesium carbonate → (2S,4R)-4-(Isoquinolin-6-ylamino)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 1621283Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH3:19][O:20][C:21]([C@@H:23]1[CH2:27][C@@H:26]([NH2:28])[CH2:25][N:24]1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:22]>CN(C=O)C>[CH3:19][O:20][C:21]([C@@H:23]1[CH2:27][C@@H:26]([NH:28][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[N:7][CH:6]=[CH:5]3)[CH2:25][N:24]1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:22]

Participants

Conditions

Temperature: 100 °C

Procedure

124 mg of 6-bromoisoquinoline (3), 488 mg of cesium carbonate and 202 mg (2S,4R)-4-amino-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester hydrochloride were dissolved in 6 ml of DMF and degassed. 46 mg Palladium acetate and 132 mg of Xanthphos were added and the mixture was stirred at 100° C. for 5 h. After cooling to rt the mixture was filtrated, evaporated and the residue was purified by chromatography on silica gel (50% ethyl acetate in heptane to 100% ethyl acetate). To obtain (2S,4R)-4-(Isoquinolin-6-ylamino)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester as a colourless oil.

Workup

customdegassed
addition46 mg Palladium acetate and 132 mg of Xanthphos were added
temperatureAfter cooling to rt the mixture
filtrationwas filtrated
customevaporated
customthe residue was purified by chromatography on silica gel (50% ethyl acetate in heptane to 100% ethyl acetate)

Sources & evidence

ORD record: ord-e7b4cdb0bc3c4bf3817a3a2f4cb62876
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772492B2

Reaction notes

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