Potassium Phosphate, Tribasic → 6-[4-(3-Hydroxypropoxy)-3-(trifluoromethyl)-phenyl]-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 912502Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[CH:11][N:12]([CH3:13])[C:4]=2[CH:3]=1.[OH:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[C:28]([F:31])([F:30])[F:29].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[N:7]=[C:6]([C:8]#[N:9])[C:5]3[N:10]=[CH:11][N:12]([CH3:13])[C:4]=3[CH:3]=2)=[CH:21][C:20]=1[C:28]([F:29])([F:30])[F:31]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 6-chloro-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (6 g), 4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenylboronic acid (12.3 g), tris(dibenzylideneacetone)dipalladium (1.42 g), tricyclohexylphosphine (1.05 g) and tribasic potassium phosphate (13.2 g) in dioxane (60 ml) and water (24 ml) was heated at 100° C. under N2 for 4 hours. The mixture was then diluted with ethyl acetate (400 ml), organic layer seperated and solvent removed under reduced pressure, to the residue was then added methanol (50 ml), product crystalised out and collected by filtration (7.7 g). 1H NMR (DMSO) δ: 8.67 (s, 1H), 8.60 (s, 1H), 8.43 (d, 1H), 8.37 (s, 1H), 7.41 (d, 1H), 4.55 (t, 1H), 4.25 (t, 2H), 3.99 (s, 3H), 3.58 (q, 2H), 1.92 (tt, 2H). MS m/z 377 (M+H).

Workup

customseperated
customsolvent removed under reduced pressure, to the residue
customadded methanol (50 ml), product crystalised out
filtrationcollected by filtration (7.7 g)

Sources & evidence

ORD record: ord-2a0c775914e040b9a6858d07c711cb19
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026236B2

Reaction notes

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