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

HRID 1910873Notes

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

Conditions

Temperature: -78 °C

Procedure

To a mixture of 5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (E-2) (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 then 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 then diluted with H2O (200 mL) and extracted with ethyl acetate (50 mL×4). The aqueous layer is acidified with con. HCl to adjust the pH to 3-4. The precipitate is then 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 (G-1).

Workup

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

Sources & evidence

ORD record: ord-f8e0b122084a4bf3926c45f2351d34f2
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08604032B2

Reaction notes

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