Cyclohexanol → 4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid cyclohexyl ester

HRID 1958425

Reaction equation

HRID 1958425 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[CH:13]1([OH:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.Cl.[CH3:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([N:31]2[C:35]3=[N:36][CH:37]=[N:38][C:39]([O:40][CH:41]4[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]4)=[C:34]3[CH:33]=[N:32]2)=[CH:27][CH:26]=1)(=[O:24])=[O:23].C(N(CC)CC)C>CN(C=O)C>[CH:13]1([O:19][C:1]([N:44]2[CH2:45][CH2:46][CH:41]([O:40][C:39]3[N:38]=[CH:37][N:36]=[C:35]4[N:31]([C:28]5[CH:29]=[CH:30][C:25]([S:22]([CH3:21])(=[O:23])=[O:24])=[CH:26][CH:27]=5)[N:32]=[CH:33][C:34]=34)[CH2:42][CH2:43]2)=[O:2])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 7966CyclohexanolHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 218977741-(4-Methanesulfonyl-phenyl)-4-(piperidin-4-yloxy)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride

Product 1

HCID 218977224-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid cyclohexyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Carbonyldiimidazole (0.28 mmol, 46 mg), and cyclohexanol (0.28 mmol, 34 μL) were dissolved in DMF (2 mL) and stirred for 30 minutes at room temperature. Then, 1-(4-Methanesulfonyl-phenyl)-4-(piperidin-4-yloxy)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride salt (0.16 mmol, 60 mg) and triethylamine (0.84 mmol, 118 μL) were added and continued to stir at 60° C. for 24 hours. The reaction mixture was quenched with water followed by an extraction with ethylacetate. Removal of organic solvents in vacuo and purification by HPLC provided compound A63 as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.67 (s, 1H); 8.61 (d, 2H); 8.26 (s, 1H); 8.11 (d, 2H); 5.62 (h, 1H); 4.71 (h, 1H); 3.91 (m, 2H); 3.38 (m, 2H); 3.10 (s, 3H); 2.10 (m, 2H); 1.87 (m, 4H), 1.65 (m, 6H); 1.28 (m, 2H). LCMS (ESI), m/z 500.4 (MH+, 100%)

Workup

  1. stirringto stir at 60° C. for 24 hours
  2. customThe reaction mixture was quenched with water
  3. extractionfollowed by an extraction with ethylacetate
  4. customRemoval of organic solvents
  5. customin vacuo and purification by HPLC
  6. customprovided compound A63 as a white solid

Sources & evidence

ORD record
ord-9cfc3c4921f04b65bea4efcb33d011c8
Source dataset
uspto-grants-2013_04
Patent number
US08410119B2

Linked notes

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