Pyruvic Acid → 6-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

HRID 751672Notes

Reaction equation

[C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=O.[Cl:7][C:8]1[CH:13]=[C:12]([NH2:14])[C:11](I)=[CH:10][N:9]=1.C1N2CCN(CC2)C1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:7][C:8]1[N:9]=[CH:10][C:11]2[CH:4]=[C:2]([C:1]([OH:6])=[O:5])[NH:14][C:12]=2[CH:13]=1

Participants

Conditions

Temperature: 145 °C

Procedure

Pyruvic acid (0.86 mL, 12.4 mmol) was added to a solution of 2-chloro-5-iodo-pyridin-4-ylamine (Preparation 115, 1.05 mg, 4.13 mmol), palladium acetate (56 mg, 0.25 mmol) and DABCO (1.39 g, 12.4 mmol) in anhydrous DMF (30 ml). The reaction mixture was degassed with argon for 20 min, then heated to 145° C. for 2 h. The solvent was removed in vacuo and the residue taken up in water (200 mL). The suspension was made alkaline (pH 9–10) with dilute NaOH solution (1M) and filtered through Celite. After washing of the filtrate with ethyl acetate (50 mL) and ether (50 mL) the pH was adjusted to 3 with dilute HCl solution (1M). Extraction with ethyl acetate (5×50 mL), drying of the combined extracts (MgSO4) and concentration gave the title compound. δH (d6 DMSO): 7.24 (1H, s), 7.42 (1H, s), 8.80 (1H, s); m/z (ES−)=195.02 [M−H]−; RT=2.36 min.

Workup

customThe reaction mixture was degassed with argon for 20 min
customThe solvent was removed in vacuo
filtrationfiltered through Celite
washAfter washing of the filtrate with ethyl acetate (50 mL) and ether (50 mL) the pH
extractionExtraction with ethyl acetate (5×50 mL)
dry with materialdrying of the combined extracts (MgSO4) and concentration

Sources & evidence

ORD record: ord-d24d81ee9aaa4d339064af4a684d4e25
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07405210B2

Reaction notes

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