Carbon Dioxide → HCID 59593131, compound

HRID 2098744Notes

Reaction equation

HRID 2098744 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[Li]CCCC.[C:22](=[O:24])=[O:23]>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:5]2[S:10][C:9]([C:22]([OH:24])=[O:23])=[CH:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 280Carbon Dioxide2×HCID 202849712-Chloro-4-(morpholin-4-yl)thieno(3,2-d)pyrimidineHCID 178418339Butyllithium

Product 1

HCID 59593131HCID 59593131, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

2-Chloro-4-morpholinothieno[3,2-d]pyrimidine 4 (2.5 g) was cooled to −78° C. in 50 mL of THF before adding 1.3 eq of a 2.5M solution of nBuLi in hexanes. The reaction was stirred at −78° C. for 30 minutes before warming to −40° C. for several minutes to allow for complete formation of the Lithium anion. The reaction was then re-cooled to −78° C. and carbon dioxide gas evolved from dry ice was bubbled in via cannula to the reaction solution for 1 hour. The reaction was then slowly warmed to 0° C. over 30 minutes and the THF was concentrated by rotovap. The reaction was then quenched with water and extracted with Ethyl Acetate to remove any 2-chloro-4-morpholinothieno[3,2-d]pyrimidine. The aqueous layer was then brought to pH of 2-3 by adding concentrated HCl. The resultant solid that crashed out of the aqueous layer was then collected by Buchner funnel, rinsed with water and dried overnight under vacuum to yield 2.65 g of 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carboxylic acid. 500 mg of this intermediate was then subjected to Procedure A. Upon extraction into Ethyl Acetate, the product remains in the aqueous layer and is treated with 20 eq of Amberlite IR-120 ion-exchange resin for 2 hours or until the solution becomes cloudy. The solution is first filtered thru a coarse Filter Flask to remove the resin and is then filtered thru a Buchner funnel to collect the 637 mg of 2-(1H-indazol-4-yl)-4-morpholinothieno[3,2-d]pyrimidine-6-carboxylic acid 13 as a light brown solid.

Workup

  1. temperaturebefore warming to −40° C. for several minutes
  2. temperatureThe reaction was then re-cooled to −78° C.
  3. customwas bubbled in via cannula to the reaction solution for 1 hour
  4. temperatureThe reaction was then slowly warmed to 0° C. over 30 minutes
  5. concentrationthe THF was concentrated by rotovap
  6. customThe reaction was then quenched with water
  7. extractionextracted with Ethyl Acetate
  8. customto remove any 2-chloro-4-morpholinothieno[3,2-d]pyrimidine
  9. additionby adding concentrated HCl
  10. customwas then collected by Buchner funnel
  11. washrinsed with water
  12. customdried overnight under vacuum

Sources & evidence

ORD record
ord-f1fe530e7ee4470eb9650a143f50f5d3
Source dataset
uspto-grants-2013_05
Patent number
US08450315B2

Reaction notes

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