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

HRID 1243229Notes

Reaction equation

HRID 1243229 reaction equation
[C:1]([Si:5]([CH3:33])([CH3:32])[O:6][C@H:7]1[CH2:11][CH2:10][C@H:9]([N:12]2[C:17]3=[N:18][C:19](Cl)=[N:20][CH:21]=[C:16]3[CH2:15][N:14]([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][CH3:30])=[CH:25][CH:24]=3)[C:13]2=[O:31])[CH2:8]1)([CH3:4])([CH3:3])[CH3:2].[F:34][C:35]1[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C.ClCCl>[C:1]([Si:5]([CH3:33])([CH3:32])[O:6][C@H:7]1[CH2:11][CH2:10][C@H:9]([N:12]2[C:17]3=[N:18][C:19]([NH:39][C:38]4[CH:40]=[CH:41][C:35]([F:34])=[CH:36][CH:37]=4)=[N:20][CH:21]=[C:16]3[CH2:15][N:14]([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][CH3:30])=[CH:25][CH:24]=3)[C:13]2=[O:31])[CH2:8]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 97314-FluoroanilineHCID 521998p-Toluenesulfonic acid monohydrateHCID 86594648(+/-)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Product 1

HCID 69584210(+/-)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-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

(±)-1-[trans-3-(tert-Butyl-dimethyl-silanyloxy)-cyclopentyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (125 mg, 0.25 mmol) (from Example 39b supra) was suspended in 2-propanol (3 mL) (Fisher). 4-Fluoroaniline (0.036 mL, 0.38 mmol) (Aldrich) and p-toluenesulfonic acid mono-hydrate (12.5 mg, 0.05 mmol) (Aldrich) were 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 (±)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a pale green solid. (Yield 123 mg, 85%).

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-30d7c115655f43d38f63f88dcb47632f
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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