Hydrochloric Acid → HCID 118522316, compound

HRID 529806Notes

Reaction equation

HRID 529806 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:39][CH:40]([F:42])[F:41])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][C:26]([N:28]3[CH2:33][CH2:32][C:31]([CH3:38])([C:34]([O:36]C)=[O:35])[CH2:30][CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:39][CH:40]([F:41])[F:42])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][C:26]([N:28]3[CH2:29][CH2:30][C:31]([CH3:38])([C:34]([OH:36])=[O:35])[CH2:32][CH2:33]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 118522805HCID 118522805, compound

Product 1

HCID 118522316HCID 118522316, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)-4-methylpiperidine-4-carboxylate (500 mg, 0.83 mmol) in methanol (10 mL) was added a solution of potassium carbonate (700 mg, 5.06 mmol) in water (5 mL). The resulting solution was stirred at 60° C. overnight and acidified with 1 N HCl to pH 2. The solids were collected by filtration. The crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005): Column, XBridge Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% FA and MeCN (30.0% MeCN up to 35.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 30.0% in 2 min); Detector, UV 254/220 nm. This resulted in 26.6 mg of 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)-4-methylpiperidine-4-carboxylic acid as a white solid. LCMS (Method 20) [M+H]+=588.2, RT=2.79 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 12.5 (br, 1H), 9.76 (s, 1H), 9.34 (d, 1H, J=6.8 Hz), 8.69-8.68 (m, 2H), 8.32 (s, 1H), 7.63 (dd, 1H, J=2.8, 8.8 Hz), 7.56 (d, 1H, J=2.8 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.29 (dd, 1H, J=4.4, 7.2 Hz), 7.08 (t, 1H, J=73.2 Hz), 5.28-5.18 (m, 2H), 3.96-3.93 (m, 1H), 3.74-3.70 (m, 1H), 3.26-3.23 (m, 1H), 3.01-2.95 (m, 1H), 1.98-1.93 (m, 2H), 1.46-1.30 (m, 2H), 1.18 (s, 3H).

Workup

  1. filtrationThe solids were collected by filtration
  2. customThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  3. waitmobile phase, water with 0.05% FA and MeCN (30.0% MeCN up to 35.0% in 10 min
  4. waitup to 95.0% in 1 min
  5. customin 1 min
  6. waitdown to 30.0% in 2 min)
  7. customThis resulted in 26.6 mg of 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)-4-methylpiperidine-4-carboxylic acid as a white solid

Sources & evidence

ORD record
ord-fd40ed70835545cfb537e4c3d85f0129
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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