p-Toluenesulfonic acid → HCID 71576985, compound

HRID 1630338Notes

Reaction equation

HRID 1630338 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[C:5]([C:10]([F:13])([F:12])[F:11])=[CH:4][N:3]=1.[CH3:14][O:15][C:16]1[CH:22]=[C:21]([N:23]2[CH:27]=[N:26][CH:25]=[N:24]2)[CH:20]=[CH:19][C:17]=1[NH2:18].C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[CH3:14][O:15][C:16]1[CH:22]=[C:21]([N:23]2[CH:27]=[N:26][CH:25]=[N:24]2)[CH:20]=[CH:19][C:17]=1[NH:18][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[C:5]([C:10]([F:13])([F:12])[F:11])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 210775872-Chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amineHCID 450914512-Methoxy-4-(1H-1,2,4-triazol-1-yl)aniline

Product 1

HCID 71576985HCID 71576985, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (80 mg, 0.38 mmol), 2-methoxy-4-(1H-1,2,4-triazol-1-yl)aniline (72 mg, 0.38 mmol) and p-toluene sulphonic acid (72 mg, 0.38 mmol) in dioxane (2 mL) was heated at 100° C. for 1 h. The mixture was cooled and filtered. The solid was partitioned between dichloromethane (10 mL) and saturated aqueous NaHCO3 (10 mL) and the product was extracted into dichloromethane (3×10 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) afforded a residue that was triturated with methanol/diethyl ether yielding N2-(2-methoxy-4-(1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine as a white solid (34.5 mg, 25%). LCMS (10 cm_ESCI_Formic_MeCN): [MH+]=366 at 3.13 min. 1H NMR (400 MHz, DMSO): δ 9.29 (s, 1H); 8.33 (d, J=8.7, 1H); 8.24-8.15 (m, 3H); 7.53 (d, J=2.4, 1H); 7.45 (dd, J=8.7, 2.4, 1H); 7.23 (d, J=5.2, 1H); 3.97 (s, 3H); 2.92 (d, J=4.4, 3H).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. customThe solid was partitioned between dichloromethane (10 mL) and saturated aqueous NaHCO3 (10 mL)
  4. extractionthe product was extracted into dichloromethane (3×10 mL)
  5. customThe combined organics were passed through a phase separation cartridge
  6. customthe solvent removed under reduced pressure
  7. customPurification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane)
  8. customafforded a residue that
  9. customwas triturated with methanol/diethyl ether

Sources & evidence

ORD record
ord-9deb1dbda192449a8309f962c677463f
Source dataset
uspto-grants-2014_07
Patent number
US08791130B2

Reaction notes

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