Methanol → (3aR,6aR)-5-Methyl-1-(4-piperazin-1-yl-phenyl)-octahydro-pyrrolo[3,4-b]pyrrole

HRID 1947398Notes

Reaction equation

HRID 1947398 reaction equation
[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][N:19](C(=O)C)[CH2:18][CH2:17]4)=[CH:12][CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1.CO>Cl>[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:11]=[CH:12][C:13]([N:16]4[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]4)=[CH:14][CH:15]=3)[CH2:6][CH2:7]2)[CH2:3]1

Participants

4

Reactant 2

HCID 887MethanolHCID 68499336(3aR,6aR)-1-{4-[4-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-phenyl]-piperazin-1-yl}-ethanone

Product 1

HCID 68497954(3aR,6aR)-5-Methyl-1-(4-piperazin-1-yl-phenyl)-octahydro-pyrrolo[3,4-b]pyrrole

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

The product of Example 49A (300 mg, 0.91 mmole) was dissolved in 6 ml of 2N hydrochloric acid and 3 ml of methanol and stirred at 60° C. for 3 hours. The mixture was concentrated to dryness under reduced pressure, diluted with water and extracted with dichloromethane (4×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure and purified by column chromatography (eluting with a mixture of 10% methanol and 1% ammonium hydroxide in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 6.84-6.94 (m, 2H) 6.53-6.60 (m, 2H) 4.00-4.07 (m, 1H) 3.44-3.51 (m, 1H) 3.11-3.20 (m, 1H) 2.99-3.09 (m, 9H) 2.88-2.96 (m, 1H) 2.68 (dd, J=9.66, 2.54 Hz, 1H) 2.48-2.59 (m, 2H) 2.31 (s, 3H) 2.09-2.19 (m, 1H) 1.89 (m, 1H). MS: (M+H)+=287.

Workup

  1. concentrationThe mixture was concentrated to dryness under reduced pressure
  2. additiondiluted with water
  3. extractionextracted with dichloromethane (4×)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by column chromatography (
  8. washeluting with a mixture of 10% methanol and 1% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-225491023be34b6fa79c22088136ea02
Source dataset
uspto-grants-2013_03
Patent number
US08399468B2

Reaction notes

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