p-Toluenesulfonic acid → HCID 71451846, compound

HRID 2406321Notes

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]([CH3:18])[CH:3]=1.Cl[C:20]1[N:25]=[C:24]([NH:26][CH3:27])[C:23]([C:28]([F:31])([F:30])[F:29])=[CH:22][N:21]=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:20]2[N:25]=[C:24]([NH:26][CH3:27])[C:23]([C:28]([F:31])([F:29])[F:30])=[CH:22][N:21]=2)=[CH:3][C:4]([CH3:18])=[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-methylphenyl)(morpholino) methanone (2.12 g, 8.47 mmol), 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (1.79 g, 8.47 mmol) and para-toluene sulfonic acid (1.62 g, 8.47 mmol) in dioxane (80 mL) was heated to 100° C. for 18 h. Saturated aqueous sodium bicarbonate solution (100 mL) and DCM (100 mL) were added, 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 (0-100% EtOAc in iso-hexane) gave (5-methoxy-2-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone (2.1 g, 58%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=426 at 2.59 min. 1H NMR (400 MHz, CDCl3): δ 8.47 (s, 1H), 8.18 (s, 1H), 7.74 (s, 1H), 6.71 (s, 1H), 5.25 (br s, 1H), 3.88 (s, 3H), 3.80 (br d, 4H), 3.59 (br s, 2H), 3.31 (br s, 2H), 3.12 (d, 3H), 2.28 (s, 3H).

Workup

customthe solvent was removed in vacuo
customPurification of the residue via silica gel column chromatography (0-100% EtOAc in iso-hexane)

Sources & evidence

ORD record: ord-e61bed9cfbeb464987bc1f65895dae9f
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809331B2

Reaction notes

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