p-Toluenesulfonic acid → (5-Methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-(trifluoromethyl)phenyl)(morpholino)methanone

HRID 2406325Notes

Reaction equation

[NH2:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[O:11])=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1.Cl[C:23]1[N:28]=[C:27]([NH:29][CH3:30])[C:26]([C:31]([F:34])([F:33])[F:32])=[CH:25][N:24]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.C(Cl)Cl>[CH3:9][O:8][C:7]1[C:2]([NH:1][C:23]2[N:28]=[C:27]([NH:29][CH3:30])[C:26]([C:31]([F:34])([F:32])[F:33])=[CH:25][N:24]=2)=[CH:3][C:4]([C:18]([F:21])([F:20])[F:19])=[C:5]([C:10]([N:12]2[CH2:13][CH2:14][O:15][CH2:16][CH2:17]2)=[O:11])[CH:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (4-amino-5-methoxy-2-(trifluoromethyl)phenyl)(morpholino)methanone (94 mg, 0.31 mmol), 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (66 mg, 0.31 mmol) and para-toluene sulfonic acid (59 mg, 0.31 mmol) in dioxane (4 mL) was heated to 100° C. for 2 h. Saturated aqueous sodium bicarbonate solution (10 mL) and DCM (10 mL) were added and the organic phase was passed through a hydrophobic frit. The solvent was removed in vacuo and the residue was purified by reversed phase HPLC to give (5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-(trifluoromethyl)phenyl)(morpholino)methanone (111 mg, 75%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=480 at 3.32 min. 1H NMR (400 MHz, CDCl3): δ 9.13 (s, 1H), 8.19 (s, 1H), 7.82 (s, 1H), 6.77 (s, 1H), 5.34 (q, J=4.7 Hz, 1H), 3.97 (s, 3H), 3.95-3.88 (m, 1H), 3.83-3.68 (m, 3H), 3.65-3.55 (m, 2H), 3.27-3.21 (m, 2H), 3.13 (d, J=4.7 Hz, 3H).

Workup

customThe solvent was removed in vacuo
customthe residue was purified by reversed phase HPLC

Sources & evidence

ORD record: ord-1bfd760dfb4341b488222be9ba5c7c24
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809331B2

Reaction notes

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