Pyrrolidine → HCID 86598342, compound

HRID 1270420Notes

Reaction equation

HRID 1270420 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[C:6]([N:8]1[C@H:13]([CH2:14][C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:12][N:11]2[CH2:24][C:25](=O)[CH2:26][CH2:27][C@@H:10]2[CH2:9]1)=[O:7].[NH:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.O.C(O)(=O)C>[F:1][C:2]([F:36])([F:37])[C:3]1[CH:4]=[C:5]([C:6]([N:8]2[C@H:13]([CH2:14][C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][CH:16]=3)[CH2:12][N:11]3[CH2:24][C@H:25]([N:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)[CH2:26][CH2:27][C@@H:10]3[CH2:9]2)=[O:7])[CH:29]=[C:30]([C:32]([F:34])([F:33])[F:35])[CH:31]=1.[F:1][C:2]([F:36])([F:37])[C:3]1[CH:4]=[C:5]([C:6]([N:8]2[C@H:13]([CH2:14][C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][CH:16]=3)[CH2:12][N:11]3[CH2:24][C@@H:25]([N:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)[CH2:26][CH2:27][C@@H:10]3[CH2:9]2)=[O:7])[CH:29]=[C:30]([C:32]([F:34])([F:33])[F:35])[CH:31]=1

Participants

9

Reactant 4

HCID 31268PyrrolidineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 18449067HCID 18449067, compound

Product 2

HCID 86598342HCID 86598342, compoundHCID 86598343HCID 86598343, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

A mixture of (3R,9aR)-2-[3,5-bis(trifluoromethyl)benzoyl]-3-(1H-indol-3-ylmethyl)-octahydro-2H-pyrido[1,2-a]pyrazin-7-one (0.785 g, see example 3 steps 1–7), pyrrolidine (0.107 g), acetic acid (0.09 g) and sodium triacetoxyborohydride (0.47 g) in 1,2-dichloroethane (60 mL) was stirred for three days at room temperature. The resulting mixture was poured into water, basified with sodium bicarbonate (5% aq. soln.) and extracted with dichloromethane. The organic layer was concentrated and the residue was purified by column chromatography (SiO2, CH2Cl2/MeOH/NH4OH 92:7.5:0.5) to afford 3,5-bis(trifluoromethyl)phenyl-[(3R,7R,9aR)-3-(1H-indol-3-ylmethyl)-7-pyrrolidin-1-yl-octahydropyrido[1,2-a]pyrazin-2-yl]-methanone (0.20 g, Rf 0.23 (CH2Cl2/MeOH/NH4OH 92:7.5:0.5)) (compound 24) and 3,5-bis(trifluoromethyl)-phenyl-[(3R,7S,9aR)-3-(1H-indol-3-ylmethyl)-7-pyrrolidin-1-yl-octahydropyrido[1,2-a]pyrazin-2-yl]-methanone (0.48 g, Rf 0.15 (CH2Cl2/MeOH/NH4OH 92:7.5:0.5)) (compound 25).

Workup

  1. extractionextracted with dichloromethane
  2. concentrationThe organic layer was concentrated
  3. customthe residue was purified by column chromatography (SiO2, CH2Cl2/MeOH/NH4OH 92:7.5:0.5)

Sources & evidence

ORD record
ord-d00eb471f22f4b87b044816c1e90a0ab
Source dataset
uspto-grants-2007_04
Patent number
US07202238B2

Reaction notes

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