N,N'-Dimethylethylenediamine → HCID 70981033, compound

HRID 1749108Notes

Reaction equation

HRID 1749108 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:46])[N:17]([C:29]1[CH:30]=[CH:31][C:32]2[NH:33][C:34](=[O:45])[N:35]([CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)[CH2:36][C:37]=2[N:38]=1)[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[O:27][CH3:28])([CH3:14])([CH3:13])[CH3:12].CNCCNC>CCOC(C)=O.[Cu]I>[C:11]([O:15][C:16](=[O:46])[N:17]([C:29]1[CH:30]=[CH:31][C:32]2[N:33]([C:7]3[CH:8]=[CH:9][C:4]([Cl:3])=[CH:5][CH:6]=3)[C:34](=[O:45])[N:35]([CH:39]3[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]3)[CH2:36][C:37]=2[N:38]=1)[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[O:27][CH3:28])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 8070N,N'-Dimethylethylenediamine2×HCID 125101-Chloro-4-iodobenzeneHCID 25953Cesium fluorideHCID 70981308HCID 70981308, compound

Product 1

HCID 70981033HCID 70981033, compoundYield 65.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Into a reaction tube were placed CsF (211 mg, 1.4 mmol, 2.5 equiv), CuI (21 mg, 0.11 mmol, 0.2 equiv), 1-chloro-4-iodo-benzene (200 mg, 0.85 mmol, 1.5 equiv), (3-cyclohexyl-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl)-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (280 mg, 0.56 mmol, 1.0 equiv) and N,N′-dimethyl-ethylene diamine (60 μL, 0.56 mmol, 1.0 equiv). The tube was sealed, evacuated and back-filled with nitrogen 3 times, then THF (5 mL) was added and the reaction mixture was heated at 80° C. overnight. Further CuI (21 mg, 0.11 mmol, 0.2 equiv) and N,N′-dimethyl-ethylene diamine (30 μL, 0.28 mmol, 0.5 equiv) were added and the heating was continued for 24 h. The reaction mixture was cooled, diluted with EtOAc and the reaction was quenched with saturated ammonium chloride. The products were extracted with ethyl acetate, the combined organic extracts were washed with brine, dried (MgSO4), filtered and the solvent evaporated. The crude material was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-500%) to afford [1-(4-chloro-phenyl)-3-cyclohexyl-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (224 mg). MS: [M+H]+=606.

Workup

  1. customInto a reaction tube were placed
  2. customThe tube was sealed
  3. customevacuated
  4. additionback-filled with nitrogen 3 times
  5. additionTHF (5 mL) was added
  6. temperatureThe reaction mixture was cooled
  7. customthe reaction was quenched with saturated ammonium chloride
  8. extractionThe products were extracted with ethyl acetate
  9. washthe combined organic extracts were washed with brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customthe solvent evaporated
  13. customThe crude material was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-500%)

Sources & evidence

ORD record
ord-be9c52be1bac4b70b05312ebd9dfea5d
Source dataset
uspto-grants-2015_10
Patent number
US09155743B2

Reaction notes

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