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

HRID 1864153Notes

Reaction equation

HRID 1864153 reaction equation
[CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:9][S:10]([C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:23]3=[N:24][CH:25]=[N:26][C:27]([O:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[C:22]3[CH:21]=[N:20]2)=[CH:15][CH:14]=1)(=[O:12])=[O:11].C(N(CC)CC)C.CN([CH:45]=[O:46])C>>[CH:1]1([O:7][C:45]([N:32]2[CH2:33][CH2:34][CH:29]([O:28][C:27]3[N:26]=[CH:25][N:24]=[C:23]4[N:19]([C:16]5[CH:17]=[CH:18][C:13]([S:10]([CH3:9])(=[O:11])=[O:12])=[CH:14][CH:15]=5)[N:20]=[CH:21][C:22]=34)[CH2:30][CH2:31]2)=[O:46])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 7966CyclohexanolHCID 8471TriethylamineHCID 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

Procedure

Carbonyldiimidizole (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-1320c0163b5a4f108f890ea4ce6c0c25
Source dataset
uspto-grants-2009_12
Patent number
US07625906B2

Reaction notes

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