Triethylamine → (3aR,6aR)-1-{4-[4-(6-Chloro-pyridazin-3-yl)-piperazin-1-yl]-phenyl}-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole

HRID 12964

Reaction equation

HRID 12964 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][NH:19][CH2:18][CH2:17]4)=[CH:12][CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1.[Cl:22][C:23]1[N:24]=[N:25][C:26](Cl)=[CH:27][CH:28]=1.C(N(CC)CC)C>C(#N)C>[Cl:22][C:23]1[N:24]=[N:25][C:26]([N:19]2[CH2:18][CH2:17][N:16]([C:13]3[CH:12]=[CH:11][C:10]([N:5]4[CH2:6][CH2:7][C@@H:8]5[CH2:9][N:2]([CH3:1])[CH2:3][C@H:4]45)=[CH:15][CH:14]=3)[CH2:21][CH2:20]2)=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 673313,6-DichloropyridazineHCID 68497954(3aR,6aR)-5-Methyl-1-(4-piperazin-1-yl-phenyl)-octahydro-pyrrolo[3,4-b]pyrrole

Product 1

HCID 24743686(3aR,6aR)-1-{4-[4-(6-Chloro-pyridazin-3-yl)-piperazin-1-yl]-phenyl}-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

The product of Example 49B (30 mg, 0.105 mmole), 3,6-dichloropyridazine (18.8 mg, 0.126 mmole), and triethylamine (45 ml, 0.036 mmole) were dissolved in 1 ml of acetonitrile and heated at 60° C. under N2 for 24 hours. The mixture was cooled to room temperature, quenched with water and extracted with dichloromethane (5×). The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure and purified by chromatography (eluting with a mixture of 0.5% ammonium hydroxide and 5% methanol in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.24 (s, 1H) 7.21 (s, 1H) 6.91-6.96 (m, 2H) 6.53-6.58 (m, 2H) 4.13-4.21 (m, 1H) 3.72-3.83 (m, 4H) 3.50-3.61 (m, 1H) 3.36-3.45 (m, 1H) 3.11-3.19 (m, 4H) 2.99-3.08 (m, 1H) 2.60-2.80 (m, 4H) 2.46 (s, 3H) 2.13-2.23 (m, 1H) 1.89-2.04 (m, 1H); MS, (M+H)+=399.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customquenched with water
  3. extractionextracted with dichloromethane (5×)
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by chromatography (
  8. washeluting with a mixture of 0.5% ammonium hydroxide and 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-6f4398a0e59a472e8a72b234a6a54dc7
Source dataset
uspto-grants-2010_06
Patent number
US07728031B2

Linked notes

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