Cesium carbonate → 2-Chloro-7,7-difluoro-5-methyl-9-(2-phenoxy-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 1676842Notes

Reaction equation

HRID 1676842 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][NH:7][C:6]=2[N:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C)C=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH2:24][CH2:25][O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:6]=2[N:16]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 18551759(2-Iodoethoxy)benzeneHCID 866375242-Chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-6H-pyrimido[4,5-b][1,4]diazepin-6-one

Product 1

HCID 866375282-Chloro-7,7-difluoro-5-methyl-9-(2-phenoxy-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 94.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.20 g (0.8 mmole) of 2-chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-292) in 2 mL of dimethylformamide was added 0.53 g (1.6 mmole) of cesium carbonate, followed by 0.8 g (3.2 mole) of (2-iodo-ethoxy)-benzene. After stirring at 50 degrees overnight, the mixture was filtered and then concentrated under reduced pressure. Dichloromethane and saturated sodium carbonate were added. The mixture was extracted twice with dichloromethane. The combined organic layers were washed three times with sodium carbonate, three times with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 0.28 g of 2-chloro-7,7-difluoro-5-methyl-9-(2-phenoxy-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-304) as an oil.

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated under reduced pressure
  3. additionDichloromethane and saturated sodium carbonate were added
  4. extractionThe mixture was extracted twice with dichloromethane
  5. washThe combined organic layers were washed three times with sodium carbonate, three times with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d353d74f300a4524b87a89577f7c3851
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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