1,4-Cyclohexadiene → methyl 2-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetate

HRID 527458Notes

Reaction equation

[C:1]([CH:3]([C:9]1[C:14]([N+:15]([O-])=O)=[CH:13][CH:12]=[C:11]([O:18][CH3:19])[N:10]=1)[CH2:4][C:5]([O:7][CH3:8])=[O:6])#N.C1CC=CCC=1>[Pd].CO>[CH3:19][O:18][C:11]1[N:10]=[C:9]2[C:3]([CH2:4][C:5]([O:7][CH3:8])=[O:6])=[CH:1][NH:15][C:14]2=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A 2 mL microwave process vial with a stir bar was charged with crude methyl 3-cyano-3-(6-methoxy-3-nitropyridin-2-yl)propanoate (50 mg, 0.19 mmol), 10% Pd/C (5 Mol %, 20 mg, 0.01 mmol), and methanol (1.5 mL). An excess of 1,4-cyclohexadiene (91 mg, 1.13 mmol) was added and the vessel flooded with argon, capped and heated under microwave conditions at 120° C. for 5 min. The reaction was filtered through CELITE® and the solvent was evaporated in vacuo. The crude material was purified by flash chromatography (SiO2, ethyl acetate/hexane gradient) to yield the product as colorless oil. C11H12N2O3, Mr=220.22; 1H NMR (400 MHz, DMSO-d6) d: 3.61 (s, 3H), 3.72 (s, 2H), 3.83 (s, 3H), 6.53 (d, J=8.8 Hz, 1H), 7.38 (d, J=2.8 Hz, 1H), 7.66 (d, J=8.4 Hz, 1H), 11.01 (bs, 1H); 13C NMR (100 MHz, DMSO-d6) d: 29.41 (s, —CH2—), 51.86 (s, —C(O)OCH3), 52.83 (s, —OCH3), 104.86 (s, C6′), 107.19 (s, C3′), 122.78 (s, C2′), 124.60 (s, C7a′), 126.80 (s, C7′), 141.29 (s, C3a′), 159.16 (s, C5′), 172.47 (s, >C═O); LCMS (ESI) tR: 0.69 min (>97%, UV220, ELSD), m/z: 221.2 [M+1]+.

Workup

customcapped
filtrationThe reaction was filtered through CELITE®
customthe solvent was evaporated in vacuo
customThe crude material was purified by flash chromatography (SiO2, ethyl acetate/hexane gradient)

Sources & evidence

ORD record: ord-4894b7f5613b48ceba39ffefab848949
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346803B2

Reaction notes

Loading…