Triethylamine → 4-chloro-8-(2,4-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 222990Notes

Reaction equation

HRID 222990 reaction equation
Cl[C:2]1[C:7]([CH:8]=O)=[C:6]([Cl:10])[N:5]=[C:4]([S:11][CH3:12])[N:3]=1.C(N(CC)CC)C.[F:20][C:21]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:22]=1[NH2:23].F[C:30](F)(F)[CH2:31][O:32]P(CC(OC)=O)(OCC(F)(F)F)=O>C1COCC1.C(Cl)Cl>[Cl:10][C:6]1[C:7]2[CH:8]=[CH:30][C:31](=[O:32])[N:23]([C:22]3[CH:24]=[CH:25][C:26]([F:28])=[CH:27][C:21]=3[F:20])[C:2]=2[N:3]=[C:4]([S:11][CH3:12])[N:5]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 97092,4-DifluoroanilineHCID 184894Nsc 634137HCID 46140044,6-Dichloro-2-(methylsulfanyl)pyrimidine-5-carbaldehyde

Product 1

HCID 119513484-chloro-8-(2,4-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 40%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,6-dichloro-2-methylsulfanyl-pyrimidine-5-carbaldehyde (4.2 g, 18.95 mmol) and triethylamine (5.3 ml, 38 mmol) in THF (100 ml) was added 2,4-difluoroaniline (2.1 ml, 20.58 mmol). The mixture was stirred for 2 h, and methyl {bis[(2,2,2-trifluoroethyl)oxy]phosphoryl}acetate (6.0 g, 18.95 mmol) was added. The mixture was stirred for 18 h, diluted with DCM (200 ml) and washed with water (2×100 ml). The dried (Na2SO4) organic phase was filtered and evaporated. Flash chromatography (EtOAc/Hexane, 1:5) provided the title compound as a cream solid (2.5 g, 40%): LC-MS m/z 340 (M+H)+ retention 3.24 min.

Workup

  1. stirringThe mixture was stirred for 18 h
  2. washwashed with water (2×100 ml)
  3. dry with materialThe dried (Na2SO4) organic phase
  4. filtrationwas filtered
  5. customevaporated

Sources & evidence

ORD record
ord-942e7bcdb66348b4a95b18838ea06874
Source dataset
uspto-grants-2012_06
Patent number
US08207176B2

Reaction notes

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