Methyl 6-chloropyridine-3-carboxylate → HCID 12862353, compound

HRID 1155873Notes

Reaction equation

HRID 1155873 reaction equation
[NH2:1][C:2]1[S:3][C:4]([CH:12]([CH3:14])[CH3:13])=[CH:5][C:6]=1[C:7]([O:9]CC)=O.Cl[C:16]1[N:21]=[CH:20][C:19]([C:22]([O:24]C)=[O:23])=[CH:18][CH:17]=1>>[CH3:14][CH:12]([C:4]1[S:3][C:2]2[N:1]=[C:16]3[CH:17]=[CH:18][C:19]([C:22]([OH:24])=[O:23])=[CH:20][N:21]3[C:7](=[O:9])[C:6]=2[CH:5]=1)[CH3:13]

Participants

3

Reactant 2

HCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 2756461ethyl 2-amino-5-isopropylthiophene-3-carboxylate

Product 1

HCID 12862353HCID 12862353, compoundYield 20.8%

Conditions

Temperature
142 °C

Procedure

A mixture of 21.33 g (0.1 mol) of 2-amino-5-(1-methylethyl)-3-thiophenecarboxylic acid, ethyl ester (Tetrahedron, Vol. 33, pages 2089-2092, 1977) and 17.16 g (0.1 mol) of 6-chloro-3-pyridinecarboxylic acid, methyl ester (Alfred Bader Chemical Company) is heated in a wax bath at 178°-182° C. for one hundred eighty-seven minutes and then at 182°-205° C. for ninety minutes under nitrogen. The distillate is collected in a Dean-Stark Trap attached to the reaction flask. The mixture is cooled, dissolved in methanol, cooled and 16.2 g of a mixture of 2-(1-methylethyl)-4-oxo-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-7-carboxylic acid, methyl ester and the ring-opened diester, 6-[[3-(ethoxycarbonyl)-5-(1-methylethyl)-2-thienyl]amino]-3-pyridinecarboxylic acid, methyl ester, is collected; mp 112°-114° C. A suspension of 11 g of the previous mixture in 250 ml of concentrated hydrochloric acid and 250 ml of water is refluxed in a wax bath at 142° C. for twenty-two hours under nitrogen. The suspension is cooled to room temperature, filtered and the precipitate washed with 300 ml of water and dried to give 6.0 g of 2-(1-methylethyl)-4-oxo-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-7-carboxylic acid; mp 264°-266° C. after recrystallization from ethanol.

Workup

  1. temperatureis heated in a wax bath at 178°-182° C. for one hundred eighty-seven minutes
  2. waitat 182°-205° C. for ninety minutes under nitrogen
  3. distillationThe distillate is collected in a Dean-Stark Trap
  4. temperatureThe mixture is cooled
  5. dissolutiondissolved in methanol
  6. temperaturecooled
  7. custom16.2 g of a mixture of 2-(1-methylethyl)-4-oxo-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-7-carboxylic acid, methyl ester and the ring-opened diester, 6-[[3-(ethoxycarbonyl)-5-(1-methylethyl)-2-thienyl]amino]-3-pyridinecarboxylic acid, methyl ester, is collected
  8. additionA suspension of 11 g of the previous mixture in 250 ml of concentrated hydrochloric acid and 250 ml of water
  9. temperatureThe suspension is cooled to room temperature
  10. filtrationfiltered
  11. washthe precipitate washed with 300 ml of water
  12. customdried

Sources & evidence

ORD record
ord-1982cffca9444ca99a6b0a02903ea72c
Source dataset
uspto-grants-1982_06
Patent number
US04332947

Reaction notes

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