Hydrochloric Acid → 2-(pyridin-4-ylamino)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one hydrochloride

HRID 1793885Notes

Reaction equation

HRID 1793885 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[H-].[Li+].CS[C:12]1[N:13]=[CH:14][C:15]2[CH:21]=[C:20]([C:22]3[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[C:24]([O:30][CH3:31])[CH:23]=3)[C:19](=[O:32])[N:18]([CH2:33][CH3:34])[C:16]=2[N:17]=1.[ClH:35]>O1CCCC1.O.C(#N)C>[ClH:35].[N:5]1[CH:6]=[CH:7][C:2]([NH:1][C:12]2[N:13]=[CH:14][C:15]3[CH:21]=[C:20]([C:22]4[CH:23]=[C:24]([O:30][CH3:31])[CH:25]=[C:26]([O:28][CH3:29])[CH:27]=4)[C:19](=[O:32])[N:18]([CH2:33][CH3:34])[C:16]=3[N:17]=2)=[CH:3][CH:4]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 17274-AminopyridineHCID 62714Lithium hydrideHCID 111991132-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one

Product 1

HCID 222201802-(pyridin-4-ylamino)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one hydrochlorideYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 88 g (0.93 mol) of 4-aminopyridine in 1 L of tetrahydrofuran was added 21.2 g (2.67 mol) of lithium hydride. The reaction mixture was heated to 50° C. for 1 hour. To the stirred reaction mixture was added a solution of 318 g (0.89 mol) of 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one in 1.8 L of tetrahydrofuran. The reaction solution was heated at reflux for 24 hours, and then cooled to 50° C. The reaction mixture was diluted by the slow addition of a mixture of 500 mL of water and 1 L of 6N hydrochloric acid. The reaction mixture was cooled to 24° C. and stirred for 16 hours. The reaction mixture was further diluted by addition of 250 mL of acetonitrile and 200 mL of water, and stirring was continued for an additional 2 hours. The mixture was then filtered, and the filter cake was dried at 45° C. in vacuo for 12 hours to provide 360 g (92%) of 2-(pyridin-4-ylamino)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one hydrochloride, mp 295–300° C. (dec). HPLC established the purity at 98%. Mass Spec (APCI) 439.89 m/z.

Workup

  1. customTo the stirred reaction mixture
  2. temperatureThe reaction solution was heated
  3. temperatureat reflux for 24 hours
  4. temperaturecooled to 50° C
  5. temperatureThe reaction mixture was cooled to 24° C.
  6. stirringstirring
  7. waitwas continued for an additional 2 hours
  8. filtrationThe mixture was then filtered
  9. customthe filter cake was dried at 45° C. in vacuo for 12 hours

Sources & evidence

ORD record
ord-5cd729bcc2054cd1ab81a68d6f1002dd
Source dataset
uspto-grants-2006_04
Patent number
US07022711B2

Reaction notes

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