Methanol → HCID 178496590, compound

HRID 717156Notes

Reaction equation

HRID 717156 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([NH:15][C@H:16]2[CH2:21][CH2:20][C@H:19]([O:22][CH3:23])[CH2:18][CH2:17]2)[C:5]([NH:8][CH2:9][C:10](OCC)=[O:11])=[N:6][CH:7]=1.CO.C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>O>[Br:1][C:2]1[N:3]=[C:4]2[N:15]([C@H:16]3[CH2:21][CH2:20][C@H:19]([O:22][CH3:23])[CH2:18][CH2:17]3)[C:10](=[O:11])[CH2:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 887Methanol2×HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 178472675HCID 178472675, compound

Product 1

HCID 178496590HCID 178496590, compoundYield 55.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

The following reaction was split into 3 separate sealed tubes and worked up separately. The material was then combined following purification. Ethyl 2-(5-bromo-3-(trans-4-methoxycyclohexylamino)pyrazin-2-ylamino)acetate (10 g, 25.7 mmol), methanol (10.5 mL, 259 mmol) and TFA (100 mL) were combined in a sealable vessel with a stirbar. The system was purged with nitrogen and the resulting mixture was sealed, stirred vigorously and heated at 90° C. with an oil bath for 18.5 h. The resulting mixture was diluted with methanol and all the solvent was removed under reduced pressure. Methanol (100 mL) was added and all the solvent was removed under reduced pressure again. Methanol (100 mL) and sodium bicarbonate (12.4 g, 147 mmol) were added. The resulting mixture was stirred at room temperature until pH=6 (in water). The mixture was concentrated nearly to dryness. Water (100 mL) was added. The resulting brown solids were collected by vacuum filtration and washed with water. The brown solids were dissolved in hot methanol and acetonitrile and purified using reverse-phase C18 flash column chromatography (20-100% acetonitrile in water). Fractions containing the desired product were combined and concentrated nearly to dryness under reduced pressure. Solids were collected by vacuum filtration, washed with water and dried under high vacuum to give the desired product (4.88 g, 14.3 mmol, 55% yield) as a light tan solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 7.71 (s, 1H), 7.59 (s, 1H), 4.66 (tt, J=3.61, 12.20 Hz, 1H), 4.07 (d, J=1.56 Hz, 2H), 3.25 (s, 3H), 3.06-3.17 (m, 1H), 2.42 (qd, J=3.51, 12.89 Hz, 2H), 2.10 (d, J=10.93 Hz, 2H), 1.61 (d, J=10.93 Hz, 2H), 1.10-1.24 (m, 2H); MS (ESI) m/z 341.3 [M]+, 343.1 [M+2]+.

Workup

  1. customThe following reaction
  2. customwas split into 3
  3. customseparate
  4. customsealed tubes
  5. custompurification
  6. customThe system was purged with nitrogen
  7. customthe resulting mixture was sealed
  8. additionThe resulting mixture was diluted with methanol and all the solvent
  9. customwas removed under reduced pressure
  10. additionMethanol (100 mL) was added
  11. customall the solvent was removed under reduced pressure again
  12. concentrationThe mixture was concentrated nearly to dryness
  13. additionWater (100 mL) was added
  14. filtrationThe resulting brown solids were collected by vacuum filtration
  15. washwashed with water
  16. dissolutionThe brown solids were dissolved in hot methanol
  17. customacetonitrile and purified
  18. additionFractions containing the desired product
  19. concentrationconcentrated nearly to dryness under reduced pressure
  20. filtrationSolids were collected by vacuum filtration
  21. washwashed with water
  22. customdried under high vacuum

Sources & evidence

ORD record
ord-c7b5d120b0f0496da51ad6f845553c8d
Source dataset
uspto-grants-2015_11
Patent number
US09193692B2

Reaction notes

Loading…