Trifluoroacetic acid → HCID 73505855, compound

HRID 590875Notes

Reaction equation

HRID 590875 reaction equation
[NH2:1][C:2]1[C:6]2[C:7]([CH3:23])=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[NH:4][N:3]=1.S([O-])([O-])(=O)=O.[Mg+2].F[C:31](F)(F)[C:32](O)=O.C([BH3-])#N.[Na+]>O.CO.C(Cl)(Cl)Cl>[CH2:31]([NH:1][C:2]1[C:6]2[C:7]([CH3:23])=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[NH:4][N:3]=1)[CH3:32]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24083Sulfuric acid magnesium salt (1:1)2×HCID 5003444Sodium cyanoborohydrideHCID 73505856HCID 73505856, compound

Product 1

HCID 73505855HCID 73505855, compoundYield 40.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

A conical vial was charged with (R) -1-(3-amino-4-methyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (32 mg, 0.103 mmol) and magnesium sulfate (37.2 mg, 0.309 mmol). chloroform (666 μl), methanol (333 μl), magnesium sulfate (37.2 mg, 0.309 mmol) and trifluroacetic acid (23.83 μl, 0.309 mmol) were injected and the reaction was stirred at ambient temperature for 1 hour. Sodium cyanoborohydride (19.44 mg, 0.309 mmol) was then added and stirring was continued for one hour. The reaction was diluted with water and the aqueous layer was transferred to a separatory funnel and washed 3×chloroform/IPA. The combined organic washings were dried over magnesium sulfate and then filtered and concentrated. The residue was dissolved in DMSO (2 mL) filtered and delivered to the purification group. Reversed phase mass triggered HPLC was performed. The active fractions were dried down on the Genevac which was free-based with NH3 in MeOH (7N) and concentrated to yield a white solid (14 mg, 40.1%). MS ESI calc'd for C18H22N6O [M+H]+ 339. found 339. 1H NMR (ppm, 500 Mhz, DMSO-d6): δ 11.52 (s, 1H), 8.88 (s, 1H), 8.39 (s, 1H), 7.45-7.09 (m, 5H), 7.00-6.95 (m, 1H), 5.41 (q, J=5.6 Hz, 1H), 4.98-4.69 (m, 1H), 3.26-3.15 (m, 2H), 2.61 (s, 3H), 1.44-1.35 (m, 3H), 1.19 (dd, J=3.6 Hz, 3H).

Workup

  1. stirringstirring
  2. waitwas continued for one hour
  3. customthe aqueous layer was transferred to a separatory funnel
  4. washwashed 3×chloroform/IPA
  5. dry with materialThe combined organic washings were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in DMSO (2 mL)
  9. filtrationfiltered
  10. customThe active fractions were dried down on the Genevac which
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-65ca7df6f0dd490cb2ae9dcd99845567
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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