Diisopropylethylamine → (S)-N-((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methyl)-2-methoxypyrimidine-5-carboxamide

HRID 509345Notes

Reaction equation

[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]([OH:11])=O)=[CH:5][N:4]=1.CCN(C(C)C)C(C)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.Cl.Cl.[F:40][C:41]1[C:42]([C@H:47]([C:49]2[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=2)[NH2:48])=[N:43][CH:44]=[CH:45][CH:46]=1>C1(C)C=CC=CC=1>[F:40][C:41]1[C:42]([C@H:47]([C:49]2[CH:54]=[CH:53][C:52]([C:55]([F:57])([F:58])[F:56])=[CH:51][CH:50]=2)[NH:48][C:9]([C:6]2[CH:7]=[N:8][C:3]([O:2][CH3:1])=[N:4][CH:5]=2)=[O:11])=[N:43][CH:44]=[CH:45][CH:46]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-methoxypyrimidine-5-carboxylic acid (80 mg, 0.519 mmol), DIPEA (0.25 mL, 1.435 mmol) in toluene (3 mL) was added DPPA (0.19 mL, 0.882 mmol). The reaction was stirred at 80° C. for 2 hours. (S)-(3-fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methanamine dihydrochloride (167 mg, 0.487 mmol) was then added as a solid in one portion. After 24 hours, the reaction was concentrated in vacuo and the residue was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 0% to 80% EtOAc in hexane, to provide the title compound as an off-white solid. 1H NMR (DMSO-d6, 400 MHz) δ ppm 9.02 (d, J=4.7 Hz, 1H), 8.97 (d, J=8.6 Hz, 1H), 8.30 (d, J=7.8 Hz, 1H), 7.63-7.77 (m, 3H), 7.54 (d, J=8.2 Hz, 2H), 7.39 (s, 1H), 7.01 (s, 1H), 6.66 (d, J=8.6 Hz, 1H), 3.93 (s, 3H) MS (ESI pos. ion) m/z: 407.0 (M+H).

Workup

waitAfter 24 hours
concentrationthe reaction was concentrated in vacuo
customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
washeluting with 0% to 80% EtOAc in hexane

Sources & evidence

ORD record: ord-c1d09ff06d4543c1950e695fd1cb6cb9
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096527B2

Reaction notes

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