1,2-Dichloroethane → HCID 57755916, compound

HRID 227708Notes

Reaction equation

HRID 227708 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]([C:14]([O:16]C)=O)=[C:12]([CH2:18][O:19][CH3:20])[NH:11][C:10](=[O:21])[NH:9]2)=[CH:4][CH:3]=1.[OH-].[Na+].[NH2:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][N:29]=[CH:28]2.C(Cl)CCl.CCN(CC)CC>CO.O.CCOC(C)=O.CN(C=O)C.CN(C1C=CN=CC=1)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[C:13]([C:14]([NH:24][C:25]3[CH:26]=[C:27]4[C:31](=[CH:32][CH:33]=3)[NH:30][N:29]=[CH:28]4)=[O:16])=[C:12]([CH2:18][O:19][CH3:20])[NH:11][C:10](=[O:21])[NH:9]2)=[CH:6][CH:7]=1

Participants

11

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 880121H-Indazol-5-amineHCID 53439029Methyl 4-(4-fluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Product 1

HCID 57755916HCID 57755916, compoundYield 40%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

The product of step (a) (4.03 g, 13.69 mmol, 1 equiv) and NaOH (2.5 N, 20 mL) were dissolved in methanol (60 mL) and heated to 60° C. in a sealed tube for four hours. The reaction mixture was diluted with water (˜50 mL) and EtOAc (˜50 mL), stirred, and separated. The aqueous layer was brought to pH 1 with 2N HCl and extracted with EtOAc. The organic layer was concentrated en vacuo and the residue (650 mg, 2.32 mmol, 1 equiv) was dissolved in DMF (13 mL). 5-aminoindazole (376 mg, 2.78 mmol, 1.2 equiv), EDC (531 mg, 2.78 mmol, 1.2 equiv), Et3N (780 μL, 5.57 mmol, 2.4 equiv) and catalytic DMAP (5 mg) were added and the mixture was heated to 80° C. in a sealed tube for two hours. The residue was dissolved in EtOAc and water and extracted. The organic layer was washed with 1N HCl, satd. NaHCO3 and Brine. The organic layer was concentrated en vacuo and then triturated with CH2Cl2/Hexane to give 368 mg of the title compound as a beige powder (40%). MS (ES+) m/e 396 [M+H]+

Workup

  1. customseparated
  2. extractionextracted with EtOAc
  3. concentrationThe organic layer was concentrated en vacuo
  4. temperaturethe mixture was heated to 80° C. in a sealed tube for two hours
  5. extractionwater and extracted
  6. washThe organic layer was washed with 1N HCl
  7. concentrationThe organic layer was concentrated en vacuo
  8. customtriturated with CH2Cl2/Hexane

Sources & evidence

ORD record
ord-064d288cf99441898e4ecfe9ba8da30c
Source dataset
uspto-grants-2009_07
Patent number
US07560467B2

Reaction notes

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