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

HRID 2406326Notes

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

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (4-amino-5-methoxy-2-(trifluoromethyl)phenyl)(morpholino)methanone (94 mg, 0.31 mmol), 2,5-dichloro-N-methylpyrimidin-4-amine (55 mg, 0.31 mmol) and para-toluene sulfonic acid (59 mg, 0.31 mmol) in dioxane (4 mL) was heated to 100° C. for 36 h. Saturated aqueous sodium bicarbonate solution (10 mL) and DCM (10 mL) were added and the organic phase was passed through a hydrophobic frit and the solvent was removed in vacuo. Purification of the residue via silica gel column chromatography (0-10% EtOAc in iso-hexane) gave (4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-5-methoxy-2-(trifluoromethyl)phenyl)(morpholino)methanone (11 mg, 8%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=446 at 3.60 min. 1H NMR (400 MHz, CDCl3): δ 8.97 (s, 1H), 8.40 (br s, 1H), 7.90 (s, 1H), 6.76 (s, 1H), 5.59 (q, J=4.9 Hz, 1H), 3.96 (s, 3H), 3.95-3.87 (m, 1H), 3.82-3.69 (m, 3H), 3.62-3.56 (m, 2H), 3.26-3.20 (m, 2H), 3.13 (d, J=4.9 Hz, 3H).

Workup

customthe solvent was removed in vacuo
customPurification of the residue via silica gel column chromatography (0-10% EtOAc in iso-hexane)

Sources & evidence

ORD record: ord-36039426315c4cfe836c51bfad7542ee
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809331B2

Reaction notes

Loading…