Potassium Fluoride → methyl 4-(3-methoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 513187Notes

Reaction equation

Cl[C:2]1[C:7]2[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[NH:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH3:15][O:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[F-].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:15][O:16][C:17]1[CH:22]=[C:21]([C:2]2[C:7]3[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[NH:10][C:6]=3[CH:5]=[CH:4][N:3]=2)[CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Intermediate A1, Methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (500 mg, 2.374 mmole), 3-methoxyphenylboronic acid (469 mg, 3.09 mmole), Pd(OAc)2 (32.0 mg, 0.142 mmole), X-Phos (113 mg, 0.237 mmole), and KF (414 mg, 7.12 mmole) were combined in 1,4-dioxane (10 mL). The mixture was degassed (3× pump/N2) then heated to 100° C. After 2 hr the mixture was cooled to RT, diluted with EtOAc, filtered through a pad of Celite washing with EtOAc, and concentrated. Flash column (Biotage-SNAP-50 g SiO2, 50% EtOAc/hexanes) gave the title compound (574 mg, 86%) as an off-white solid. 1H NMR (399 MHz, CDCl3): δ 9.26 (bs, 1 H); 8.51 (d, J=5.8 Hz, 1 H); 7.58-7.51 (m, 3 H); 7.50-7.40 (m, 1 H); 7.30 (d, J=5.9 Hz, 1 H); 7.03 (dd, J=8.2, 2.6 Hz, 1 H); 3.97 (s, 3 H); 3.91 (s, 3 H).

Workup

customThe mixture was degassed (3× pump/N2)
temperatureAfter 2 hr the mixture was cooled to RT
additiondiluted with EtOAc
filtrationfiltered through a pad of Celite
washwashing with EtOAc
concentrationconcentrated

Sources & evidence

ORD record: ord-c4d14e8389d546a0a408577b4f905e41
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102673B2

Reaction notes

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