3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione → (+)-cis-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4(1H-indol-3-yl)pyrrolidine-2,5-dione

HRID 541015Notes

Reaction equation

[H][H].[C:3]1([C:15]2[C:16](=[O:30])[NH:17][C:18](=[O:29])[C:19]=2[C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[NH:22][CH:21]=2)[C:13]2=[C:14]3[C:9](=[CH:10][CH:11]=[CH:12]2)[CH2:8][CH2:7][CH2:6][N:5]3[CH:4]=1.CC(C)([O-])C.[K+]>[OH-].[Pd+2].[OH-].C1COCC1>[C:3]1([C@H:15]2[C@@H:19]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][CH:21]=3)[C:18](=[O:29])[NH:17][C:16]2=[O:30])[C:13]2=[C:14]3[C:9](=[CH:10][CH:11]=[CH:12]2)[CH2:8][CH2:7][CH2:6][N:5]3[CH:4]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Palladium hydroxide (20 wt % Pd on carbon, 11.5 kg) was charged to a properly prepared reaction vessel. THF (340 kg) was added to produce a slurry, and the catalyst was prereduced with hydrogen (50-75 psi). Compound 6 (115 kg) was charged to an empty vessel followed by THF (353 kg). The resulting mixture was stirred until dissolution was complete. The solution of Compound 6 was then transferred to the slurry of the catalyst. A solution of potassium tert-butoxide (1.6 M in THF, 36 kg) was charged to an empty reactor followed by THF (21 kg). This resulting solution was also transferred to the reaction mixture followed by an additional rinse with THF (340 kg). The batch was then heated to 45-55° C. under 65-80 psi of hydrogen. It is not necessary to isolate the intermediate cis racemate (±)-cis-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione (Compound 7 in Scheme I).

Workup

customto produce a slurry
washan additional rinse with THF (340 kg)

Sources & evidence

ORD record: ord-6a0e552a29a34a63937f71b592370546
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871933B2

Reaction notes

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