Methanol → HCID 178488242, compound

HRID 898050Notes

Reaction equation

HRID 898050 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:33]3[CH2:38][CH2:37][C@H:36]([NH:39][CH2:40][CH2:41][C:42]([O:44]CC)=[O:43])[CH2:35][CH2:34]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=4F)=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12.[O:47]1CCOC[CH2:48]1.[OH-].[K+].CO>O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:33]3[CH2:34][CH2:35][C@H:36]([NH:39][CH2:40][CH2:41][C:42]([OH:44])=[O:43])[CH2:37][CH2:38]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:21][C:20]=4[O:47][CH3:48])=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12

Participants

6

Reactant 4

HCID 887MethanolHCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 178472043HCID 178472043, compound

Product 1

HCID 178488242HCID 178488242, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of trans-ethyl 3-({4-[4-amino-3-(4-{[2-fluoro-4-trifluoromethylbenzoyl]amino}-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl}amino)propanoate (0.04 g, 0.06 mmol), p-dioxane (4 mL), potassium hydroxide (0.02 g, 0.31 mmol), a trace amount of methanol and water (0.4 mL) were heated at 80° C. for 1 hour. The mixture was stirred at ambient temperature overnight and at 80° C. for 4 hours. The solvents were evaporated and the residue was purified by preparative HPLC to yield trans-3-({4-[4-amino-3-(3-methoxy-4-{[2-methoxy-4-trifluoromethylbenzoyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl}amino)propanoic acid (0.04 g, 0.06 mmol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.72 (s, 1H), 8.61(d, 1H), 8.28 (d, 1H), 8.24 (s, 1H), 7.61(s, 1H), 7.53 (d, 1H), 7.33 (s, 1H), 7.29 (d, 1H), 4.72 (m, 1H), 4.20 (s, 3H), 4.05 (s, 3H), 1.44-3.61 (m, 13H); RP-HPLC (Hitachi HPLC, Hypersil C18, 5 μm, 100 A, 250×4.6 mm; 25%-100% acetonitrile-0.05M ammonium acetate over 10 min, 1 mL/min) Rt 6.36 min.

Workup

  1. customThe solvents were evaporated
  2. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-40fa0fb9f1c64ff480e1531e5157880d
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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