Dichloromethane → HCID 66612160, compound

HRID 1621863Notes

Reaction equation

HRID 1621863 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:26][C:27]4[CH:28]=[N:29][C:30]([O:34][CH3:35])=[C:31]([F:33])[CH:32]=4)=[N:18][CH:19]=[C:20]([CH:25]=3)[C:21]([O:23][CH3:24])=[O:22])[N:10]=2)=CC=1.OS(C(F)(F)F)(=O)=O.C(=O)(O)[O-].[Na+].C(Cl)Cl>C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[C:17]([NH:26][C:27]3[CH:28]=[N:29][C:30]([O:34][CH3:35])=[C:31]([F:33])[CH:32]=3)=[N:18][CH:19]=[C:20]([CH:25]=2)[C:21]([O:23][CH3:24])=[O:22])[N:10]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 62406Trifluoromethanesulfonic acid2×HCID 516892Sodium BicarbonateHCID 66612194HCID 66612194, compound

Product 1

HCID 66612160HCID 66612160, compoundYield 67.3%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinate (0.965 g, 1.542 mmol) and triflic acid (0.685 mL, 7.71 mmol), in 6 mL TFA was heated in a flask fitted with a reflux condenser and drying tube at 80° C. for 30 min. The dark red reaction was cooled and triflic acid (0.685 mL, 7.71 mmol) was added, and the reaction was reheated to 80° C. After 30 min, the reaction was judged complete. The reaction was cooled to 0° C., and ice was added, along with solid sodium bicarbonate, in portions, with rapid stirring. DCM was added. Upon complete quenching of acid, the thick mixture was extracted with 3×10% iPrOH/DCM, 2×10% iPrOH/EtOAc (EtOAc layers were washed 1× brine). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The solid was suspended in diethyl ether, sonicated, and filtered, rinsing with 3× diethyl ether to give methyl 5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinate (0.400 g, 1.038 mmol, 67.3% yield) as an orange solid. m/z (ESI, +ve ion) 386 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.37 (s, 1H), 9.26 (d, J=2.3 Hz, 1H), 8.83 (d, J=2.3 Hz, 1H), 8.41 (d, J=2.3 Hz, 1H), 8.31 (dd, J=12.4, 2.2 Hz, 1H), 8.01 (br. s., 1H), 7.84 (br. s., 1H), 3.95 (s, 3H), 3.88 (s, 3H), 2.46 (s, 3H).

Workup

  1. customfitted with a reflux condenser
  2. customdrying tube at 80° C. for 30 min
  3. customThe dark red reaction
  4. temperaturewas cooled
  5. customwas reheated to 80° C
  6. customUpon complete quenching of acid
  7. extractionthe thick mixture was extracted with 3×10% iPrOH/DCM, 2×10% iPrOH/EtOAc (EtOAc layers were washed 1× brine)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customsonicated
  12. filtrationfiltered
  13. washrinsing with 3× diethyl ether

Sources & evidence

ORD record
ord-2ae8595e1e5e4f9892aeaf31f6fb5110
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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