Hydrochloric Acid → HCID 118522681, compound

HRID 529805Notes

Reaction equation

HRID 529805 reaction equation
C([O-])([O-])=O.[K+].[K+].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([O:44][CH:45]([F:47])[F:46])=[C:12]([C:14]2[C:18]([NH:19][C:20]([C:22]3[CH:23]=[N:24][N:25]4[CH:30]=[CH:29][CH:28]=[N:27][C:26]=34)=[O:21])=[CH:17][N:16]([CH2:31][C:32]([N:34]3[CH2:39][CH2:38][CH:37]([C:40]([O:42]C)=[O:41])[CH2:36][CH2:35]3)=[O:33])[N:15]=2)[CH:13]=1.Cl>O.CO>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([O:44][CH:45]([F:46])[F:47])=[C:12]([C:14]2[C:18]([NH:19][C:20]([C:22]3[CH:23]=[N:24][N:25]4[CH:30]=[CH:29][CH:28]=[N:27][C:26]=34)=[O:21])=[CH:17][N:16]([CH2:31][C:32]([N:34]3[CH2:35][CH2:36][CH:37]([C:40]([OH:42])=[O:41])[CH2:38][CH2:39]3)=[O:33])[N:15]=2)[CH:13]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 118522475HCID 118522475, compound

Product 1

HCID 118522681HCID 118522681, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

K2CO3 (500 mg, 3.59 mmol) in H2O (5 mL) was added to methyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidine-4-carboxylate (500 mg, 0.85 mmol) in methanol (10 mL). The resulting solution was stirred at 50° 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 34.0% 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 390 mg (80%) of 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]-acetyl)piperidine-4-carboxylic acid as a light yellow solid. LCMS (Method 28) [M+H]+=574.1, RT=1.11 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 12.34 (s, 1H), 9.76 (s, 1H), 9.34 (dd, 1H, J=1.6, 7.2 Hz), 8.69-8.67 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.8, 8.8 Hz), 7.55 (d, 1H, J=2.4 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.28 (dd, 1H, J=4.4, 6.8 Hz), 7.08 (t, 1H, J=73.2 Hz), 5.29-5.19 (m, 2H), 4.28-4.18 (m, 1H), 3.87-3.84 (m, 1H), 3.19-3.13 (m, 1H), 2.83-2.77 (m, 1H), 1.86-1.85 (m, 2H), 1.60-1.57 (m, 1H), 1.43-1.41 (m, 2H).

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 34.0% 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 390 mg (80%) of 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]-acetyl)piperidine-4-carboxylic acid as a light yellow solid

Sources & evidence

ORD record
ord-390f226c09974c0da0a290b902bd38ae
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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