Toluene → (+/-)-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

HRID 1243228Notes

Reaction equation

HRID 1243228 reaction equation
[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][C@H:7]1[CH2:11][CH2:10][C@H:9]([NH:12][C:13]2[C:18]([CH2:19][NH:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH3:28])=[CH:23][CH:22]=3)=[CH:17][N:16]=[C:15]([Cl:29])[N:14]=2)[CH2:8]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:39](Cl)(Cl)=[O:40].C1(C)C=CC=CC=1>ClCCl.CN(C)C1C=CN=CC=1>[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][C@H:7]1[CH2:11][CH2:10][C@H:9]([N:12]2[C:13]3=[N:14][C:15]([Cl:29])=[N:16][CH:17]=[C:18]3[CH2:19][N:20]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH3:28])=[CH:23][CH:22]=3)[C:39]2=[O:40])[CH2:8]1)([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 1140TolueneHCID 6371PhosgeneHCID 8471TriethylamineHCID 86594647(+/-)-[trans-3-(Tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-{2-chloro-5-[(4-ethyl-phenylamino)-methyl]-pyrimidin-4-yl}-amine

Product 1

HCID 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

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (±)-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-{2-chloro-5-[(4-ethyl-phenylamino)-methyl]-pyrimidin-4-yl}-amine (270 mg, 0.58 mmol) (from Example 39a supra) and triethylamine (0.25 mL, 1.76 mmol) (Allied Signal) in dichloromethane (6 mL) was cooled to 0° C. A 20% phosgene in toluene solution (0.32 mL, 0.61 mmol) (Fluka) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The mixture was allowed to warm up to room temperature and 4-(dimethylamino)pyridine (15 mg, 0.12 mmol) (Aldrich) was added. The reaction was stirred at room temperature overnight, heated at reflux for 4 hours, and then concentrated to dryness. The yellow residue was purified by flash chromatography (20% ethyl acetate in hexanes) to give (±)-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. (Yield 213 mg, 75%).

Workup

  1. temperatureto warm up to room temperature
  2. stirringThe reaction was stirred at room temperature overnight
  3. temperatureheated
  4. temperatureat reflux for 4 hours
  5. concentrationconcentrated to dryness
  6. customThe yellow residue was purified by flash chromatography (20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5a112d29517d47d389344b942a6b7310
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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