4-Fluoroaniline → (R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

HRID 1243225Notes

Reaction equation

HRID 1243225 reaction equation
[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][CH2:7][C@H:8]([N:10]1[C:15]2=[N:16][C:17](Cl)=[N:18][CH:19]=[C:14]2[CH2:13][N:12]([C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH3:28])=[CH:23][CH:22]=2)[C:11]1=[O:29])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[F:32][C:33]1[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=1>CC(O)C.ClCCl>[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][CH2:7][C@H:8]([N:10]1[C:15]2=[N:16][C:17]([NH:37][C:36]3[CH:38]=[CH:39][C:33]([F:32])=[CH:34][CH:35]=3)=[N:18][CH:19]=[C:14]2[CH2:13][N:12]([C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH3:28])=[CH:23][CH:22]=2)[C:11]1=[O:29])[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 97314-FluoroanilineHCID 11271157(R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Product 1

HCID 11364631(R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
160 °C

Procedure

(R)-1-[2-(tert-Butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (100 mg, 0.21 mmol) (from Example 38e supra) was suspended in 2-propanol (2 mL) (Fisher). 4-Fluoroaniline (0.03 mL, 0.32 mmol) (Aldrich) was added and the mixture was heated to 160° C. in a microwave synthesizer (SmithSynthesizer™) for 30 minutes. After cooling to room temperature, the heterogeneous reaction mixture was diluted with dichloromethane. The resulting solution was washed with 1 N aqueous hydrochloric acid. The layers were separated and the organic phase was dried over anhydrous sodium sulfate, filtered and then concentrated under reduce pressure to give (R)-1-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a pale yellow solid. (Yield 107 mg, 91%).

Workup

  1. temperatureAfter cooling to room temperature
  2. washThe resulting solution was washed with 1 N aqueous hydrochloric acid
  3. customThe layers were separated
  4. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-efbe2e417d0d48499cfa49f4f5905405
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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