2-Chloropyridin-4-amine → 6-(3,5-Dimethoxy-phenyl)-2-(2-chloro-pyridin-4-ylamino)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 1793883Notes

Reaction equation

HRID 1793883 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=1.C([Li])CCC.[CH3:14][O:15][C:16]1[CH:17]=[C:18]([C:24]2[C:36](=[O:37])[N:35]([CH2:38][CH3:39])[C:27]3[N:28]=[C:29](S(C)=O)[N:30]=[CH:31][C:26]=3[CH:25]=2)[CH:19]=[C:20]([O:22][CH3:23])[CH:21]=1.C(OCC)(=O)C.O>C1COCC1>[CH3:23][O:22][C:20]1[CH:19]=[C:18]([C:24]2[C:36](=[O:37])[N:35]([CH2:38][CH3:39])[C:27]3[N:28]=[C:29]([NH:1][C:2]4[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=4)[N:30]=[CH:31][C:26]=3[CH:25]=2)[CH:17]=[C:16]([O:15][CH3:14])[CH:21]=1

Participants

6

Reactant 4

HCID 844322-Chloropyridin-4-amineHCID 222201672-methylsulfinyl-6-(3,5-dimethoxy-phenyl)8-ethyl-8H-pyrido[2,3-d]pyrimidine-7-oneHCID 22728543Water ethylacetateHCID 178418339Butyllithium

Product 1

HCID 222201706-(3,5-Dimethoxy-phenyl)-2-(2-chloro-pyridin-4-ylamino)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-oneYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a −78° C. solution of 4.1 g (32.1 mmol) of 4-amino-2-chloropyridine in 120 mL of THF was added dropwise 17.5 mL (30.5 mmol) of 1.6 M n-butyllithium in hexanes. The reaction solution was stirred for 15 minutes at which time 3.0 g (8.0 mmol) of the product of Example 7, 6-(3,5-dimethoxy-phenyl)-8-ethyl-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one, was added in small portions as a solid. The reaction mixture was allowed to warm slowly to −10° C. then remain at −10° C. overnight. The reaction mixture was poured into ethyl acetate/water/5 mL 6N HCl. The mixture was shaken and separated. The organic phase was washed with a saturated solution of sodium bicarbonate, twice with water, and brine, then dried over magnesium sulfate, filtered, and concentrated to a volume of about 200 mL. The suspension was stirred overnight and filtered to give a yellow solid. The solid was triturated under 20 mL of 1:9 methanol/chloroform, filtered, and dried to give 1.89 g (54%) of the titled compound.

Workup

  1. additionwas added in small portions as a solid
  2. customseparated
  3. washThe organic phase was washed with a saturated solution of sodium bicarbonate, twice with water, and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a volume of about 200 mL
  7. stirringThe suspension was stirred overnight
  8. filtrationfiltered
  9. customto give a yellow solid
  10. customThe solid was triturated under 20 mL of 1:9 methanol/chloroform
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-af8dc3b814db402193cafbc46fa121a3
Source dataset
uspto-grants-2006_04
Patent number
US07022711B2

Reaction notes

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