Carbon Dioxide → 4-Chloro-7H-pyrrolo(2,3-d)pyrimidine-5-carboxylic acid

HRID 1051769Notes

Reaction equation

HRID 1051769 reaction equation
Br[C:2]1[C:10]2[C:9]([Cl:11])=[N:8][CH:7]=[N:6][C:5]=2[NH:4][CH:3]=1.[Li]CCCC.[C:17](=[O:19])=[O:18]>C1COCC1.O>[Cl:11][C:9]1[C:10]2[C:2]([C:17]([OH:19])=[O:18])=[CH:3][NH:4][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 3

HCID 280Carbon DioxideHCID 53807105-Bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 224608664-Chloro-7H-pyrrolo(2,3-d)pyrimidine-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (G-1) (6.24 g, 26.8 mmol, 1.0 eq) in anhydrous THF (100 mL) at −78° C. under argon, n-BuLi solution (2.5 M in THF, 23.6 mL, 59.0 mmol, 2.2 eq) is added dropwise over 30 min. The reaction mixture is stirred at −78° C. for 1 h and then dry ice (300 g) is added in portions under an argon atmosphere. The resulting mixture is allowed to warm to RT and then stirred at RT overnight. The reaction mixture is diluted with H2O (200 mL) and extracted with ethyl acetate (50 mL×4). The aqueous layer is acidified with conc. HCl to adjust the pH to 3-4. The precipitate is collected by filtration, rinsed with H2O (30 mL) and dried in vacuo to afford the product, 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (H-1).

Workup

  1. temperatureto warm to RT
  2. stirringstirred at RT overnight
  3. extractionextracted with ethyl acetate (50 mL×4)
  4. filtrationThe precipitate is collected by filtration
  5. washrinsed with H2O (30 mL)
  6. customdried in vacuo

Sources & evidence

ORD record
ord-3c1f556fb6434853be7d42b3473a1773
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

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