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

HRID 1864153

Reaktionsgleichung

Reaktionsgleichung von HRID 1864153
[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

Komponenten

5

Edukt 4

HCID 6228DimethylformamideHCID 7966CyclohexanolHCID 8471TriethylamineHCID 218977741-(4-Methanesulfonyl-phenyl)-4-(piperidin-4-yloxy)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride

Produkt 1

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

Versuchsvorschrift

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%)

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-1320c0163b5a4f108f890ea4ce6c0c25
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07625906B2

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