Chloride → HCID 68421745, compound

HRID 1993350Notes

Reaction equation

HRID 1993350 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23](=[O:30])[N:24]([CH3:29])[C:25](O)=[N:26][CH:27]=2)=[CH:18][C:17]=1[F:31].CN(C)C1C=CC=CC=1.[Cl-:41]>O=P(Cl)(Cl)Cl>[Cl:41][C:25]1[N:24]([CH3:29])[C:23](=[O:30])[C:22]([C:19]2[CH:20]=[CH:21][C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][CH:7]=3)=[C:17]([F:31])[CH:18]=2)=[CH:27][N:26]=1

Participants

5

Reactant 3

HCID 312ChlorideHCID 949N,N-DimethylanilineHCID 178486806HCID 178486806, compound

Product 1

HCID 68421745HCID 68421745, compound

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

5-(4-(6,7-Dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-2-hydroxy-3-methyl-3H-pyrimidin-4-one (Step 2, 678.8 mg, 1.605 mmol) was dissolved in POCl3 (16 mL) and N,N-dimethylaniline (1.6 ml) and heated at 125° C. for 8.5 h then cooled to RT and stirred overnight. The reaction was concentrated, diluted with CH2Cl2 (125 mL) and washed with saturated NaHCO3 (25 mL, 17 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Because of the propensity of title compound to hydrolysis, the crude chloride was used for the next reaction.

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with CH2Cl2 (125 mL)
  3. washwashed with saturated NaHCO3 (25 mL, 17 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customBecause of the propensity of title compound to hydrolysis

Sources & evidence

ORD record
ord-21ca7e16da6c46e28be1aa058b827bc1
Source dataset
uspto-grants-2010_01
Patent number
US07652009B2

Reaction notes

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