Potassium Hydroxide → HCID 178488241, compound

HRID 898049Notes

Reaction equation

HRID 898049 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]=4[F:29])=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12.O1CCOCC1.[OH-].[K+]>O>[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]([OH:44])=[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:27])([F:28])[F:26])=[CH:21][C:20]=4[F:29])=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 178472042HCID 178472042, compound

Product 1

HCID 178488241HCID 178488241, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of cis-ethyl 3-({4-[4-amino-3-(4-{[2-fluoro-4trifluoromethylbenzoyl]amino}-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl}amino)propanoate (0.23 g, 0.36 mmol), p-dioxane (15 mL), potassium hydroxide (0.10 g, 1.81 mmol) and water (1.5 mL) were heated at 80° C. for 3 hours. The solvents were evaporated and the residue was purified by preparative HPLC to yield cis-3-({4-[4-amino-3-(4-{[2-fluoro-4-trifluoromethylbenzoyl]amino}-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl}amino)propanoic acid (0.11 g, 0.18 mmol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 9.91 (dd, 1H), 8.31 (d, 1H), 8.25 (s, 1H), 8.00 (t, 1H), 7.89 (d, 1H), 7.75 (d, 1H), 7.35 (s, 1H), 7.32 (s, 1H), 6.89 (br, 2H), 4.79 (m, 1H), 3.95 (s, 3H), 2.46-3.00 (m, 7H), 2.29 (m, 2H), 1.91 (m, 2H), 1.80 (m, 2H); 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 6.06 min. MS: MH+ 616.

Workup

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

Sources & evidence

ORD record
ord-a747ad3929734386a07fc4c39c9fdd4e
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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