Dichloromethane → HCID 53251814, compound

HRID 1039627Notes

Reaction equation

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

Participants

Reactant 2

HCID 6344Dichloromethane

HCID 11494412Tivantinib2×

Product 1

HCID 53251814HCID 53251814, compound

Procedure

The present invention also provides a method for preparing (−)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione, comprising: (a) dissolving (±)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione in dichloromethane and isolating the (±)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione dichloromethane; (b) dissolving (±)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione dichloromethane in a first solvent; (c) distilling the solution of step (b) until the level of dichloromethane in the solution is <0.1% by weight; (d) diluting the solution of step (c) in a second solvent; (e) introducing the solution of step (d) into a multicolumn chromatography system containing a packing suitable for chiral separation; (f) pooling the resultant raffinate obtained from the system in step (e); and (g) crystallizing the raffinate from step (f) and filtering the resultant (−)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione or evaporating the raffinate from step (f) to dryness, thereby producing (−)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione. Preferably, the produced (−)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione comprises less than 1%, less than 0.7%, less than 0.5% or less than 0.1% (+)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione.

Workup

customThe present invention also provides a method

Sources & evidence

ORD record: ord-4a6e34c5169c46e5afd8308337c236eb
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552192B2

Reaction notes

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