Pyrrolidine → 1-(4-Methoxy-phenyl)-6-(2-oxo-2-pyrrolidin-1-yl-ethyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

HRID 720435Notes

Reaction equation

HRID 720435 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.C[Al](C)C.C[O:11][C:12](=O)[CH2:13][N:14]1[CH2:19][CH2:18][C:17]2[C:20]([C:31]([F:34])([F:33])[F:32])=[N:21][N:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C:16]=2[C:15]1=[O:35]>C(Cl)Cl>[CH3:30][O:29][C:26]1[CH:27]=[CH:28][C:23]([N:22]2[C:16]3[C:15](=[O:35])[N:14]([CH2:13][C:12](=[O:11])[N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:19][CH2:18][C:17]=3[C:20]([C:31]([F:34])([F:32])[F:33])=[N:21]2)=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 10339907[1-(4-Methoxy-phenyl)-7-oxo-3-trifluoromethyl-1,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridin-6-yl]-acetic acid methyl esterHCID 16682925Trimethylaluminum

Product 1

HCID 98023301-(4-Methoxy-phenyl)-6-(2-oxo-2-pyrrolidin-1-yl-ethyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Part A: Pyrrolidine (0.152 mL, 1.826 mmol) was dissolved in methylene chloride (6 mL) and cooled to 0° C. 2M Trimethylaluminum (0.652 mL, 1.304 mmol) was added to the reaction and stirred for 30 min at 0° C. [1-(4-Methoxy-phenyl)-7-oxo-3-trifluoromethyl-1,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridin-6-yl]-acetic acid methyl ester (0.100 g, 0.261 mmol) was added and the reaction was stirred overnight at rt. The reaction was quenched with water (100 mL), extracted into methylene chloride (3×50 mL), washed with brine (1×50 mL), dried over MgSO4, concentrated, and purified, by flash chromatography using 0–100% ethyl acetate/hexanes gradient and methanol flush as eluents, followed by further purification by reverse phase HPLC. Freeze-drying afforded 0.052 g (47%): 1H NMR (CDCl3) δ 7.38 (d, j=8.8 Hz, 2H), 6.87 (d, j=9.1 Hz, 2H), 4.15 (s, 2H), 3.77 (t, j=6.8 Hz, 2H), 3.76 (s, 3H), 3.40(t, j=6.8 Hz, 2H), 3.33 (t, j=6.8 Hz, 2H), 3.00(t, j=6.8 Hz, 2H), 1.92–1.85 (m, 2H), 1.82–1.73 (m, 2H) ppm; Mass Spec 423.3(M+H)+.

Workup

  1. additionwas added
  2. customThe reaction was quenched with water (100 mL)
  3. extractionextracted into methylene chloride (3×50 mL)
  4. washwashed with brine (1×50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. custompurified, by flash chromatography
  8. customflush as eluents
  9. customfollowed by further purification by reverse phase HPLC
  10. customFreeze-drying
  11. customafforded 0.052 g (47%)

Sources & evidence

ORD record
ord-d4c421ef9b3a4a86ada5844940541889
Source dataset
uspto-grants-2006_11
Patent number
US07135469B2

Reaction notes

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