Methyl 5-chloro-2-(3-fluorophenyl)-6-[(formylamino)methyl]nicotinate → Methyl 8-chloro-5-(3-fluorophenyl)imidazo[1,5-a]pyridine-6-carboxylate

HRID 717819Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH2:19][NH:20][CH:21]=O)=[N:4][C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]>P(Cl)(Cl)(Cl)=O>[Cl:1][C:2]1[C:3]2[N:4]([CH:21]=[N:20][CH:19]=2)[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Methyl 5-chloro-2-(3-fluorophenyl)-6-[(formylamino)methyl]nicotinate (2.6 g, 8.5 mmol) was stirred in phosphoryl chloride (80 mL) and heated at 90° C. for 1 hour. Evaporation and purification by flash column chromatography with ethyl acetate in hexanes (0-100%) gave the desired compound (0.60 g, 40%). LCMS calculated for C15H11ClFN2O2 (M+H)+: m/z=305.1. found: 304.9. 1H NMR (300 MHz, DMSO-d6): δ 8.26 (s, 1H), 7.91 (s, 1H), 7.60 (m, 1H), 7.43 (m, 3H), 7.38 (m, 1H), 3.60 (s, 3H).

Workup

customEvaporation and purification by flash column chromatography with ethyl acetate in hexanes (0-100%)

Sources & evidence

ORD record: ord-fb8aeb739efa46268a11c5f7419426ee
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193721B2

Reaction notes

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