Sodium hydride → HCID 178504255, compound

HRID 1280593Notes

Reaction equation

HRID 1280593 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13](S(C)(=O)=O)=[N:14][CH:15]=2)[NH:10][C:9]1=[O:22].[H-].[Na+].[CH3:25][Si:26]([CH3:33])([CH3:32])[CH2:27][CH2:28][O:29][CH2:30]Cl.[NH2:34][C@H:35]1[CH2:40][CH2:39][C@H:38]([NH2:41])[CH2:37][CH2:36]1>CN1CCCC1=O.[Cl-].[Na+].O>[NH2:34][C@H:35]1[CH2:40][CH2:39][C@H:38]([NH:41][C:13]2[N:12]=[C:11]3[N:10]([CH2:30][O:29][CH2:28][CH2:27][Si:26]([CH3:33])([CH3:32])[CH3:25])[C:9](=[O:22])[N:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])[CH2:17][C:16]3=[CH:15][N:14]=2)[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 184254033-(2-chloro-phenyl)-7-methylsulfonyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-oneHCID 178511674HCID 178511674, compound

Product 1

HCID 178504255HCID 178504255, compoundYield 62.7%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of sulfone 11.1 (3.0 g, 8.87 mmol) in 10 mL of 1-methyl-2-pyrrolidinone was added 60% sodium hydride (390 mg, 9.76 mmol, mineral oil). The reaction was stirred for 15 minutes at room temperature and then 2-(trimethylsilyl)ethoxymethyl chloride (1.57 mL, 8.87 mmol) was added. The reaction was stirred at room temperature for 4 hours. To this solution was then added 5.06 g of trans-1,4-diaminocyclohexane predissolved in 15 mL 1-methyl-2-pyrrolidinone. The reaction was then warmed to 60° C. for 24 hours. The reaction was poured into brine and the product extracted into ethyl acetate. The combined organic extracts were washed with saturated sodium bicarbonate and water, dried over magnesium sulfate, and concentrated in vacuo to give a light brown oil. Purification by chromatography using 2% methanol/dichloromethane to 5% methanol/dichloromethane as eluant gave 2.8 g of 7-(trans-4-aminocyclohexylamino)-3-(2-chlorophenyl)-1-[2-(trimethylsilyl)ethoxymethyl]-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one as a pale yellow foam. (MH+=502).

Workup

  1. stirringThe reaction was stirred at room temperature for 4 hours
  2. temperatureThe reaction was then warmed to 60° C. for 24 hours
  3. extractionthe product extracted into ethyl acetate
  4. washThe combined organic extracts were washed with saturated sodium bicarbonate and water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a light brown oil
  8. customPurification by chromatography

Sources & evidence

ORD record
ord-b0a40c818f764daba5c1127ad7e9e86e
Source dataset
uspto-grants-2002_09
Patent number
US06451804B1

Reaction notes

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