HCID 178490945, compound → HCID 178491168, compound

HRID 1525233Notes

Reaction equation

HRID 1525233 reaction equation
[OH:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[N:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1.Cl.[NH2:18][CH:19]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[C:20]1[CH:25]=[CH:24][C:23]([PH:26](=[O:28])[OH:27])=[CH:22][CH:21]=1>S(Cl)(Cl)=O.ClCCl>[OH:1][C:2]1[C:7]([C:8]([NH:18][CH:19]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[C:20]2[CH:25]=[CH:24][C:23]([PH:26](=[O:27])[OH:28])=[CH:22][CH:21]=2)=[O:10])=[CH:6][N:5]=[C:4]([C:11]2[N:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1

Participants

5

Reactant 2

HCID 178490945HCID 178490945, compoundHCID 178524753HCID 178524753, compound

Product 1

HCID 178491168HCID 178491168, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxylic acid, 30-ie, (545 mg, 2.5 mmol) in 5 ml of thionyl chloride was heated at reflux overnight. Then it was concentrated under vacuum and the residue was dissolved in 10 ml of dichloromethane. To the mixture was added 4-(amino(4-methoxyphenyl)methyl)phenylphosphinic acid hydrochloride (1-1-e, 782.5 mg, 2.5 mmol) and TEA (505 mg, 5 mmol) in 10 ml of dichloromethane at 0° C. The mixture was stirred for 3 hours and then it was washed with sat. NH4Cl. The organic layer was concentrated under vacuum and the residue was purified on prep-HPLC to provide the product 9-2 (150 mg, 12%). 1H NMR (CD3OD, 300 MHz,): δ 9.37 (m, 1H), 8.83 (s, 1H), 8.51 (m, 1H), 8.15 (m, 1H), 7.80 (m, 2H), 7.53 (m, 2H), 7.23 (m, 2H), 6.79 (m, 2H), 6.56 (s, 1H), 6.34 (s, 1H), 3.77 (s, 3H).

Workup

  1. temperatureat reflux overnight
  2. concentrationThen it was concentrated under vacuum
  3. dissolutionthe residue was dissolved in 10 ml of dichloromethane
  4. washit was washed with sat. NH4Cl
  5. concentrationThe organic layer was concentrated under vacuum
  6. customthe residue was purified on prep-HPLC

Sources & evidence

ORD record
ord-0cc9f848ecde4ca5bc88e192e0bf9a86
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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