Water → HCID 178491936, compound

HRID 1243164Notes

Reaction equation

HRID 1243164 reaction equation
C([Si](C)(C)[O:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([N:13]2[C:18]3=[N:19][C:20]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[N:21][CH:22]=[C:17]3[CH2:16][N:15]([C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[C:14]2=[O:38])[CH2:9][CH2:8]1)(C)(C)C.O>FC(F)(F)C(O)=O.ClCCl>[OH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([N:13]2[C:18]3=[N:19][C:20]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[N:21][CH:22]=[C:17]3[CH2:16][N:15]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)[C:14]2=[O:38])[CH2:9][CH2:8]1

Participants

5

Reactant 2

HCID 962WaterHCID 178491937HCID 178491937, compound

Product 1

HCID 178491936HCID 178491936, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

1-[trans-4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (from Example 3b supra) (139 mg, 0.25 mmol) was dissolved at 0° C. in a 50% solution of trifluoroacetic acid in dichloromethane (5 mL) that contained water (330 μL). After stirring for 1.5 hours the reaction mixture was partitioned between ethyl acetate and 1 N aqueous sodium hydroxide and the pH of the aqueous layer was adjusted to 12 by adding solid sodium hydroxide. The organic layer was then washed with water, dried over sodium sulfate, filtered and concentrated to the crude product. Purification by silica gel column chromatography with 0–100% ethyl acetate in hexanes gradient followed by a precipitation out of tetrahydrofuran with excess of pentane afforded 1-(trans-4-hydroxy-cyclohexyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as an off-white solid. (Yield 72 mg, 65%).

Workup

  1. customwas partitioned between ethyl acetate and 1 N aqueous sodium hydroxide
  2. additionby adding solid sodium hydroxide
  3. washThe organic layer was then washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to the crude product
  7. customPurification by silica gel column chromatography with 0–100% ethyl acetate in hexanes gradient
  8. customfollowed by a precipitation out of tetrahydrofuran with excess of pentane

Sources & evidence

ORD record
ord-f2c99716fe144edabfc565315a71056b
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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