Potassium Carbonate → 5-[(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-2-(6-methylpyridazin-3-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine

HRID 1713164Notes

Reaction equation

HRID 1713164 reaction equation
Cl.[CH3:2][C:3]1[N:8]=[N:7][C:6]([N:9]2[CH:17]=[C:12]3[CH2:13][NH:14][CH2:15][CH2:16][C:11]3=[N:10]2)=[CH:5][CH:4]=1.Cl[CH2:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([CH:28]2[CH2:31][CH2:30][CH2:29]2)[CH2:24][CH2:23]1)=[O:21].C([O-])([O-])=O.[K+].[K+]>CC#N>[CH:28]1([N:25]2[CH2:26][CH2:27][N:22]([C:20](=[O:21])[CH2:19][N:14]3[CH2:15][CH2:16][C:11]4=[N:10][N:9]([C:6]5[N:7]=[N:8][C:3]([CH3:2])=[CH:4][CH:5]=5)[CH:17]=[C:12]4[CH2:13]3)[CH2:23][CH2:24]2)[CH2:31][CH2:30][CH2:29]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 574205621-(Chloroacetyl)-4-cyclobutylpiperazineHCID 668769962-(6-methylpyridazin-3-yl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine hydrochloride

Product 1

HCID 574207005-[(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-2-(6-methylpyridazin-3-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-(6-methylpyridazin-3-yl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine hydrochloride (920 mg, 3.65 mmol), 1-(chloroacetyl)-4-cyclobutylpiperazine (791 mg, 3.65 mmol), K2CO3 (2.52 g, 18.3 mmol) and KI (66 mg, 0.4 mmol) in CH3CN (20 ml) is stirred at rt overnight. The solvent is removed in vacuo and the residue is partitioned between water (20 mL) and EtOAc (20 mL). The layers are separated and the aqueous layer is extracted with EtOAc (3×20 mL). The combined extracts are washed with brine (30 mL), dried and evaporated. The resulting oil is purified by flash column with DCM/MeOH/NH4OH (100:5:0.5) to give the title compound as a light yellow solid. 1H NMR (δ, CDCl3): 8.43 (s, 1H), 8.01 (d, 1H), 7.41 (d. 1H), 3.64-3.67 (m, 6H), 3.40 (s, 2H), 2.88 (s, 4H), 2.66-2.72 (m, 4H), 2.29 (q, 4H), 1.59-2.05 (m, 6H). MS (M+1): 396.2.

Workup

  1. customThe solvent is removed in vacuo
  2. customthe residue is partitioned between water (20 mL) and EtOAc (20 mL)
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted with EtOAc (3×20 mL)
  5. washThe combined extracts are washed with brine (30 mL)
  6. customdried
  7. customevaporated
  8. customThe resulting oil is purified by flash column with DCM/MeOH/NH4OH (100:5:0.5)

Sources & evidence

ORD record
ord-d229c5966213472b91a3946170ea5d73
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

Loading…