Carbonic Acid → 1-[5-(4-Isoquinolin-6-yl-benzoyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-propan-1-one

HRID 1482942Notes

Reaction equation

Br[C:2]1[CH:21]=[CH:20][C:5]([C:6]([N:8]2[CH2:12][CH:11]3[CH2:13][N:14]([C:16](=[O:19])[CH2:17][CH3:18])[CH2:15][CH:10]3[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[CH:22]1[C:31]2[C:26](=[CH:27][C:28](B(O)O)=[CH:29][CH:30]=2)[CH:25]=[CH:24][N:23]=1.C(O)(O)=O>O1CCOCC1>[CH:22]1[C:31]2[C:26](=[CH:27][C:28]([C:2]3[CH:21]=[CH:20][C:5]([C:6]([N:8]4[CH2:12][CH:11]5[CH2:13][N:14]([C:16](=[O:19])[CH2:17][CH3:18])[CH2:15][CH:10]5[CH2:9]4)=[O:7])=[CH:4][CH:3]=3)=[CH:29][CH:30]=2)[CH:25]=[CH:24][N:23]=1

Participants

Conditions

Temperature: 150 °C

Procedure

1.4 1-[5-(4-Bromo-benzoyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-propan-1-one (100 mg; 0.285 mmol) and isoquinolin-6-ylboronic acid (55.2 mg; 0.31 mmol) are dissolved in 1,4-dioxane dried (max. 0.005% H2O), SeccoSolv® (5.0 ml; 0.058 mol) and the mixture is purged with nitrogen for 5 minutes. Sodium carbonate anhydrous (90.6 mg , 0.86 mmol) and bis(triscyclohexyl-phosphine)-palladium(II) dichloride, 99% (6.4 mg, 8.7 μM) are added and the reaction mixture is heated to 150° C. for 90 min under microwave. The mixture is extracted with ethyl acetate/water. The organic layer is dried over MgSO4, filtered off and evaporated in vacuo. The product is purified on prep. HPLC to afford 56 mg (49%) 1-[5-(4-isoquinolin-6-yl-benzoyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-propan-1-one (“A1”) as a white solid;

Workup

dry with materialdried (max. 0.005% H2O), SeccoSolv® (5.0 ml; 0.058 mol)
customthe mixture is purged with nitrogen for 5 minutes
extractionThe mixture is extracted with ethyl acetate/water
dry with materialThe organic layer is dried over MgSO4
filtrationfiltered off
customevaporated in vacuo
customThe product is purified on prep

Sources & evidence

ORD record: ord-b3f6db45ece74f73b723fcb1602f5ba3
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416133B2

Reaction notes

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