Methylamine → 3-[6,7,8,9-tetrahydro-8-[(methylamino)methyl]pyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione hydrochloride

HRID 863669Notes

Reaction equation

HRID 863669 reaction equation
FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C(O[CH2:20][CH:21]1[CH2:50][CH2:49][N:24]2[C:25]3[C:30]([C:31]([C:32]4[C:33](=O)[O:34][C:35](=[O:47])[C:36]=4[C:37]4[C:45]5[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=5)[N:39]([CH3:46])[CH:38]=4)=[C:23]2[CH2:22]1)=[CH:29][CH:28]=[CH:27][CH:26]=3)(=O)C.[N:51]1[C:56](C)=CC(C)=CC=1C.C[NH2:61].[Cl:62]CCl>>[ClH:62].[CH3:56][NH:51][CH2:20][CH:21]1[CH2:50][CH2:49][N:24]2[C:25]3[C:30]([C:31]([C:32]4[C:33](=[O:34])[NH:61][C:35](=[O:47])[C:36]=4[C:37]4[C:45]5[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=5)[N:39]([CH3:46])[CH:38]=4)=[C:23]2[CH2:22]1)=[CH:29][CH:28]=[CH:27][CH:26]=3

Participants

6

Reactant 5

HCID 6329Methylamine2×HCID 6344Dichloromethane2×HCID 79532,4,6-TrimethylpyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 103898823-[8-(Acetoxymethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)furan-2,5-dione

Product 1

HCID 196964163-[6,7,8,9-tetrahydro-8-[(methylamino)methyl]pyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione hydrochloride

Procedure

265 mg of trifluoromethanesulfonic anhydride in 40 ml of dichloromethane were treated at 0° C. under a nitrogen atmosphere with a suspension of 200 mg of the pyrroledione product of Example 1 and 100 mg of collidine in 30 ml of dichloromethane. After 5 hours, 0.75 ml of a 33% solution of methylamine in methylated spirit was added and the mixture was stirred for 18 hours. An additional 0.5 ml of the aforementioned methylamine solution was then added. After 4 hours, the solvent was removed by evaporation and the precipitate was filtered off and purified by chromatography on silica gel with dichloromethane/methanol/acetic acid/water (90:18:3:2). The solid product was stirred with ethyl acetate saturated with hydrogen chloride for 2 hours. The resulting solid was filtered off and dried to give 55 mg of 3-[6,7,8,9-tetrahydro-8-[(methylamino)methyl]pyrido[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione hydrochloride of melting point 337°-340° C.

Workup

  1. waitAfter 4 hours
  2. customthe solvent was removed by evaporation
  3. filtrationthe precipitate was filtered off
  4. custompurified by chromatography on silica gel with dichloromethane/methanol/acetic acid/water (90:18:3:2)
  5. stirringThe solid product was stirred with ethyl acetate saturated with hydrogen chloride for 2 hours
  6. filtrationThe resulting solid was filtered off
  7. customdried

Sources & evidence

ORD record
ord-ec2da7851c3c418487e3f74e94a19245
Source dataset
uspto-grants-1998_02
Patent number
US05721245

Reaction notes

Loading…