Morpholine → HCID 11519961, compound

HRID 1270419Notes

Reaction equation

HRID 1270419 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([C:13]([N:15]2[C@H:20]([CH2:21][C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[NH:24][CH:23]=3)[CH2:19][N:18]3[CH2:31][CH:32](Br)[CH2:33][CH2:34][C@@H:17]3[CH2:16]2)=[O:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>C(#N)C>[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([C:13]([N:15]2[C@H:20]([CH2:21][C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[NH:24][CH:23]=3)[CH2:19][N:18]3[CH2:31][C@H:32]([N:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)[CH2:33][CH2:34][C@@H:17]3[CH2:16]2)=[O:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([C:13]([N:15]2[C@H:20]([CH2:21][C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[NH:24][CH:23]=3)[CH2:19][N:18]3[CH2:31][C@@H:32]([N:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)[CH2:33][CH2:34][C@@H:17]3[CH2:16]2)=[O:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 86598339HCID 86598339, compound

Product 2

HCID 11519961HCID 11519961, compoundHCID 86598341HCID 86598341, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3,5-bis(trifluoromethyl)phenyl-[(3R,9aR)-7-bromo-3-(1H-indol-3-ylmethyl)-octahydropyrido[1,2-a]pyrazin-2-yl]-methanone (2.94 g) and morpholine (0.92 mL) in acetonitrile (100 mL) was heated at 80° C. for 40 hours. After cooling to room temperature the mixture was concentrated in vacuo and the residue purified by flash-chromatography (SiO2, CH2Cl2/MeOH/NH4OH 980:18.75:1.25) to afford 3,5-bis(trifluoromethyl)phenyl-[(3R,7R,9aR)-3-(1H-indol-3-ylmethyl)-7-morpholin-4-yl-octahydropyrido[1,2-a]pyrazin-2-yl]-methanone (1.6 g, Rf 0.33 (CH2Cl2/MeOH/NH4OH 92:7.5:0.5)) (compound 13) and 3,5-bis(trifluoromethyl)phenyl-[(3R,7S,9aR)-3-(1H-indol-3-ylmethyl)-7-morpholin-4-yl-octahydropyrido[1,2-a]pyrazin-2-yl]-methanone (1.28 g, Rf 0.27 (CH2Cl2/MeOH/NH4OH 92:7.5:0.5)) (compound 14).

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. concentrationwas concentrated in vacuo
  3. customthe residue purified by flash-chromatography (SiO2, CH2Cl2/MeOH/NH4OH 980:18.75:1.25)

Sources & evidence

ORD record
ord-d59fb28b88f84a84b52c94a27740243a
Source dataset
uspto-grants-2007_04
Patent number
US07202238B2

Reaction notes

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