p-Toluenesulfonic acid → HCID 71455393, compound

HRID 2406322Notes

Reaction equation

[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[O:10])=[C:4]([CH3:17])[CH:3]=1.Cl[C:19]1[N:24]=[C:23]([NH:25][CH3:26])[C:22]([C:27]([F:30])([F:29])[F:28])=[CH:21][N:20]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.C(Cl)Cl>[Cl:8][C:7]1[C:2]([NH:1][C:19]2[N:24]=[C:23]([NH:25][CH3:26])[C:22]([C:27]([F:30])([F:28])[F:29])=[CH:21][N:20]=2)=[CH:3][C:4]([CH3:17])=[C:5]([C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[O:10])[CH:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (4-amino-5-chloro-2-methylphenyl)(morpholino)methanone (79 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 4 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-chloro-2-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone (71 mg, 53%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=430 at 3.47 min. 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H), 8.21 (d, 1H), 7.57 (s, 1H), 7.22 (s, 1H), 5.30 (br s, 1H), 3.79 (br d, 4H), 3.60 (br s, 2H), 3.32 (br s, 2H), 3.11 (d, 3H), 2.32 (s, 3H).

Workup

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

Sources & evidence

ORD record: ord-e1feeebe09bc4e17b07fb5b890720b3f
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809331B2

Reaction notes

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