Hydrochloric Acid → HCID 118208537, compound

HRID 595295Notes

Reaction equation

HRID 595295 reaction equation
[O-:1][C:2]#[N:3].[K+].Cl.[CH3:6][C:7]1[CH:8]=[C:9]([C:24]2[CH:25]=[N:26][N:27]([CH2:29][C:30]3([OH:36])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[CH:28]=2)[CH:10]=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:12]=1.C(=O)(O)[O-].[Na+]>C1COCC1.CCOC(C)=O.O>[OH:36][C:30]1([CH2:29][N:27]2[CH:28]=[C:24]([C:9]3[CH:10]=[C:11]([NH:13][C:14]4[N:19]=[C:18]([C:20]([F:22])([F:23])[F:21])[CH:17]=[CH:16][N:15]=4)[CH:12]=[C:7]([CH3:6])[CH:8]=3)[CH:25]=[N:26]2)[CH2:35][CH2:34][N:33]([C:2]([NH2:3])=[O:1])[CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 516892Sodium BicarbonateHCID 11378442Potassium cyanate2×HCID 118216573HCID 118216573, compound

Product 1

HCID 118208537HCID 118208537, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

Potassium cyanate (55.6 mg, 0.69 mmol), water (2.4 mL) and hydrochloric acid (2.0 M in water, 0.3 mL, 0.60 mmol) were added to a solution of racemic 4-((4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)methyl)piperidin-4-ol (49 mg, 0.11 mmol) in THF (0.8 mL). The mixture was stirred at 55° C. for 3.5 hours. Additional hydrochloric acid standard solution (2.0 M in water, 0.15 mL, 0.30 mmol) and potassium cyanate (20.0 mg, 0.25 mmol) were added. The mixture was heated for another 2 hours then saturated sodium bicarbonate and EtOAc were added. The organic phase was washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified on reverse phase HPLC (ACN/water with 0.1% TFA modifier) to afford 4-hydroxy-4-((4-(3-methyl-5((4-(trifluoromethyl) pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)methyl) piperidine-1-carboxamide. MS ESI calc'd for C22H25F3N7O2 [M+H]+476. found 476. 1H NMR (500 MHz, CD3OD) δ 8.68 (d, J=4.9, 1H), 7.96 (s, 1H), 7.84 (s, 1H), 7.82 (s, 1H), 7.37 (s, 1H), 7.10 (s, 1H), 7.09 (d, J=4.9, 1H), 4.16 (s, 2H), 3.78 (d, J=13.2, 2H), 3.20 (t, J=11.3, 2H), 2.35 (s, 3H), 1.71-1.56 (m, 2H), 1.48 (d, J=13.1, 2H).

Workup

  1. temperatureThe mixture was heated for another 2 hours
  2. washThe organic phase was washed with water, brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on reverse phase HPLC (ACN/water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-7bb4390dfa54461eab4292432390855a
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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