N,N'-Dimethylethylenediamine → [1,3-Bis-(4-chloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester

HRID 1749100Notes

Reaction equation

HRID 1749100 reaction equation
[F-].[Cs+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7](I)=[CH:6][CH:5]=1.[C:11]([O:15][C:16](=[O:40])[N:17]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][C:31]=1[O:38][CH3:39])[C:18]1[CH:19]=[CH:20][C:21]2[NH:22][C:23](=[O:28])[NH:24][CH2:25][C:26]=2[N:27]=1)([CH3:14])([CH3:13])[CH3:12].CN[CH2:43][CH2:44]NC>[Cu]I>[C:11]([O:15][C:16](=[O:40])[N:17]([C:18]1[CH:19]=[CH:20][C:21]2[N:22]([C:44]3[CH:43]=[CH:9][C:4]([Cl:3])=[CH:5][CH:6]=3)[C:23](=[O:28])[N:24]([C:7]3[CH:8]=[CH:9][C:4]([Cl:3])=[CH:5][CH:6]=3)[CH2:25][C:26]=2[N:27]=1)[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][C:31]=1[O:38][CH3:39])([CH3:14])([CH3:13])[CH3:12].[C:11]([O:15][C:16](=[O:40])[N:17]([C:18]1[CH:19]=[CH:20][C:21]2[N:22]([C:7]3[CH:8]=[CH:9][C:4]([Cl:3])=[CH:5][CH:6]=3)[C:23](=[O:28])[NH:24][CH2:25][C:26]=2[N:27]=1)[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][C:31]=1[O:38][CH3:39])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 125101-Chloro-4-iodobenzeneHCID 25953Cesium fluorideHCID 70981319(2,4-Dimethoxy-benzyl)-(2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl)-carbamic acid tert-butyl ester

Product 2

HCID 70981244[1,3-Bis-(4-chloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl esterHCID 70981608[1-(4-Chloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
80 °C

Procedure

Into a reaction tube were placed CsF (1.0 g, 6.5 mmol, 2.5 equiv), CuI (50 mg, 0.26 mmol, 0.1 equiv), 1-chloro-4-iodo-benzene (740 mg, 3.12 mmol, 1.2 equiv), (2,4-dimethoxy-benzyl)-(2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl)-carbamic acid tert-butyl ester (Example 20, product from Step 4) (1.09 g, 2.6 mmol, 1.0 equiv) and N,N′-dimethyl-ethylene diamine (280 μL, 2.6 mmol, 1.0 equiv). The tube was sealed, evacuated and back-filled with nitrogen, then acetonitrile (5 mL) was added and the reaction mixture was heated at 80° C. overnight. The reaction mixture was cooled, diluted with ethyl acetate and the reaction was quenched with saturated ammonium chloride. The products were extracted with ethyl acetate, the combined organics were washed with brine, dried (MgSO4), filtered and the solvent evaporated. The crude material was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-100%) to afford 490 mg of [1,3-bis-(4-chloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (high RF compound, MS: [M+H]+=635) and 383 mg of [1-(4-chloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (low RF compound, MS: [M+H]+=525).

Workup

  1. customInto a reaction tube were placed
  2. customThe tube was sealed
  3. customevacuated
  4. additionback-filled with nitrogen
  5. additionacetonitrile (5 mL) was added
  6. temperatureThe reaction mixture was cooled
  7. additiondiluted with ethyl acetate
  8. customthe reaction was quenched with saturated ammonium chloride
  9. extractionThe products were extracted with ethyl acetate
  10. washthe combined organics were washed with brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customthe solvent evaporated
  14. customThe crude material was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-100%)

Sources & evidence

ORD record
ord-0f65b946311546c0978efcdf24d38f41
Source dataset
uspto-grants-2015_10
Patent number
US09155743B2

Reaction notes

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