Citric Acid → (4-{8-[4-(4-Isopropylpiperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}pyridin-2-yl)methanol

HRID 1783978Notes

Reaction equation

HRID 1783978 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[C:18]4[N:19]([N:34]=[CH:35][N:36]=4)[C:20]([C:23]4[CH:28]=[CH:27][N:26]=[C:25]([CH2:29][O:30]C(=O)C)[CH:24]=4)=[CH:21][N:22]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[CH:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17]3[C:18]4[N:19]([N:34]=[CH:35][N:36]=4)[C:20]([C:23]4[CH:28]=[CH:27][N:26]=[C:25]([CH2:29][OH:30])[CH:24]=4)=[CH:21][N:22]=3)=[CH:14][CH:15]=2)[CH2:8][CH2:9]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 57590057Acetic acid 4-{8-[4-(4-isopropylpiperazin-1-yl)phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}pyridin-2-ylmethyl ester

Product 1

HCID 24890468(4-{8-[4-(4-Isopropylpiperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}pyridin-2-yl)methanolYield 12.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetic acid 4-{8-[4-(4-isopropylpiperazin-1-yl)phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}pyridin-2-ylmethyl ester is stirred at room temperature overnight in 10 mL of a 1.5 M solution of potassium carbonate in methanol. The pH is then brought to neutral by addition of 10% aqueous citric acid and the mixture is extracted with DCM. Purification by LC using 98/2 DCM/2M NH3 in MeOH as the eluent provides the title compound as a yellow powder (40.3 mg, 12.5% over 2 steps). 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 1.02 (6H, m), 2.33 (1H, m), 2.60 (4H, br m), 3.10 (4H, br m), 4.65 (2H, d), 5.51 (1H, t), 6.96 (2H, d), 7.84-7.89 (3H, m), 8.11 (1H, s), 8.17 (1H, m), 8.61 (1H, d), 8.73 (1H, m), 10.08 (1H, s). LCMS: Rt=0.78 min (100%), m/z (ESI) 445 (M+H)+.

Workup

  1. extractionthe mixture is extracted with DCM
  2. customPurification by LC

Sources & evidence

ORD record
ord-45edd5e34d214dc19202bd9f88e1479c
Source dataset
uspto-grants-2009_03
Patent number
US07501411B2

Reaction notes

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