ChemicalBook CAS DataBase List MK -1439 intermediate

MK -1439 intermediate synthesis

9synthesis methods

Product Name:MK -1439 intermediate
CAS Number:1155846-86-8
Molecular formula:C13H6ClF3N2O2
Molecular Weight:314.65

2,4-Pentadienoic acid, 2-(3-chloro-5-cyanophenoxy)-5-ethoxy-3-(trifluoromethyl)-, ethyl ester, (4E)-

1613307-28-0
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1155846-86-8
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Yield:1155846-86-8 18.54 g

Reaction Conditions:

with ammonia in methanol;toluene at 60; for 18 h;

Steps:

4.2 Cyclization, Diene C to E 3-Chloro-5-((2-oxo-4-(trifluoromethyl)-l,2-dihydropyridin-3-yl)oxy)benzonitrile (E):

To a solution of diene C in PhMe/MeOH (573 mL; 40.69 g, 104.4 mmol theoretical C) was charged methanol (25 mL, 0.61 vol). Ammonia (32 g, 1.88 mol, 18 equiv based on theoretical C) was added and the solution was warmed to 60 °C. The reaction was aged at 60 °C for 18 h. The temperature was adjusted to 35-45 °C and the pressure was decreased maintain a productive distillation rate. The batch volume was reduced to -300 mL and methanol (325 mL, 8 vol) was charged in portions to maintain a batch volume between 250 and 350 mL. The heating was stopped and the system vented. The resulting slurry was cooled to room temperature and aged overnight. The batch was filtered and the cake washed with methanol (3x, 45 mL). The wet cake was dried on the frit with suction under a nitrogen stream to afford 18.54 g of a white solid: ^XH NMR (DMSO-i/₆, 500 MHz): δ 12.7 (br s, 1H), 7.73 (t, 1H, J= 1.5 Hz), 7.61-7.59 (m, 2H), 7.53 (t, 1H, J= 2.0 Hz), 6.48 (d, 1H, J= 7.0 Hz) ppm.

References:

WO2014/89140,2014,A1 Location in patent:Page/Page column 23; 24; 25

557-21-1 Synthesis