Potassium Phosphate, Tribasic → 3-Amino-6-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-4-(methylamino)picolinonitrile

HRID 517985Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:19]=[CH:18][C:12]([O:13][CH2:14][CH2:15][CH2:16][OH:17])=[C:11]([C:20]([F:23])([F:22])[F:21])[CH:10]=2)O1.[NH2:25][C:26]1[C:27]([C:35]#[N:36])=[N:28][C:29](Cl)=[CH:30][C:31]=1[NH:32][CH3:33].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>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]>[NH2:25][C:26]1[C:27]([C:35]#[N:36])=[N:28][C:29]([C:9]2[CH:19]=[CH:18][C:12]([O:13][CH2:14][CH2:15][CH2:16][OH:17])=[C:11]([C:20]([F:21])([F:22])[F:23])[CH:10]=2)=[CH:30][C:31]=1[NH:32][CH3:33]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoro-methyl)phenoxy)propan-1-ol (34 g), 3-amino-6-chloro-4-(methylamino)picolinonitrile (16.2 g), potassium phosphate (56.5 g), tricyclohexylphosphine (2.98 g), and tris(dibenzylideneacetone)dipalladium(0) (4.06 g) in dioxane (340 ml) and water (170 ml) under N2 was heated to 100° C. for 2 hours then diluted with ethyl acetate and filtered through celite. The organic layer was separated, dried over magnesium sulphate and solvent removed under reduced pressure to give expected product clean enough for use in the next step (49.6 g). 1H NMR (CD3OD) δ: 8.06 (s, 1H), 8.01 (d, 1H), 7.23 (d, 1H), 6.86 (s, 1H), 4.23 (t, 2H), 3.78 (t, 2H), 2.98 (s, 3H), 2.04 (quin, 2H). MS m/z 367 (M+H).

Workup

filtrationfiltered through celite
customThe organic layer was separated
dry with materialdried over magnesium sulphate and solvent
customremoved under reduced pressure

Sources & evidence

ORD record: ord-1e9ac33218ca48d689d76fb9ab466b4f
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115126B2

Reaction notes

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