Diisopropylethylamine → (S)-1-(2-Methoxypyrimidin-5-yl)-3-((4-(trifluoromethyl)-phenyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)urea

HRID 1622564Notes

Reaction equation

HRID 1622564 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6](C(O)=O)=[CH:5][N:4]=1.CC[N:14]([CH:18](C)C)C(C)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:28])=CC=1.Cl.[F:39][C:40]([F:60])([F:59])[C:41]1[CH:46]=[CH:45][C:44]([C@@H:47]([C:49]2[C:54]([C:55]([F:58])([F:57])[F:56])=[CH:53][CH:52]=[CH:51][N:50]=2)[NH2:48])=[CH:43][CH:42]=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[N:4]=[CH:5][C:6]([NH:14][C:18]([NH:48][C@@H:47]([C:44]2[CH:43]=[CH:42][C:41]([C:40]([F:59])([F:39])[F:60])=[CH:46][CH:45]=2)[C:49]2[C:54]([C:55]([F:58])([F:56])[F:57])=[CH:53][CH:52]=[CH:51][N:50]=2)=[O:28])=[CH:7][N:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 64866182-Methoxypyrimidine-5-carboxylic acidHCID 86687962(S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine Hydrochloride2×

Product 1

HCID 86688143(S)-1-(2-Methoxypyrimidin-5-yl)-3-((4-(trifluoromethyl)-phenyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 2-methoxypyrimidine-5-carboxylic acid (57 mg, 0.370 mmol), DIPEA (0.161 mL, 0.925 mmol), and toluene (3 mL) was added DPPA (0.104 mL, 0.481 mmol). The reaction was stirred at 80° C. for 2 h. (S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine hydrochloride (Intermediate 1) (134 mg, 0.376 mmol) was then added as a solid in one portion. After 16 h, the reaction was concentrated in vacuo and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 0-100% EtOAc in hexane, to provide the title compound as an off-white solid. 1H NMR (300 MHz, CDCl3): δ ppm 8.96 (s, 2H), 8.90 (d, J=3.8 Hz, 1H), 8.22 (d, J=7.5 Hz, 1H), 8.05 (d, J=6.9 Hz, 1H), 7.63-7.45 (m, 6H), 6.85 (d, J=7.7 Hz, 1H), 4.07 (s, 3H). MS (ESI pos. ion) m/z: 472.0 (M+H).

Workup

  1. additionwas then added as a solid in one portion
  2. concentrationthe reaction was concentrated in vacuo
  3. customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
  4. washeluting with 0-100% EtOAc in hexane

Sources & evidence

ORD record
ord-04ffde46f5c9485f9c6b213af71f8640
Source dataset
uspto-grants-2014_07
Patent number
US08778941B2

Reaction notes

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