Hydrochloric Acid → HCID 118522551, compound

HRID 529814Notes

Reaction equation

HRID 529814 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:41][CH:42]([F:44])[F:43])=[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][N:31]([CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])[CH2:30][CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1.[OH-].[K+].O.Cl>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:41][CH:42]([F:44])[F:43])=[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][N:31]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])[CH2:32][CH2:33]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14797Potassium HydroxideHCID 118522574HCID 118522574, compound

Product 1

HCID 118522551HCID 118522551, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 3-[4-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperazin-1-yl]propanoate (270 mg, 0.43 mmol) in ethanol (10 mL) was added KOH (200 mg, 3.56 mmol) and water (4 mL). The resulting solution was stirred at room temperature for 1 h and neutralized with 1 N HCl solution. The resulting mixture was concentrated under vacuum. 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 (27.0% up to 35.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 27.0% in 2 min); Detector, UV 254/220 nm. This resulted in 31.5 mg (11%) of the formic acid salt of 3-[4-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]-acetyl)piperazin-1-yl]propanoic acid as a off-white solid. LCMS (Method 28) [M+H]+=603.1, RT=0.81 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.34 (dd, 1H, J=1.4, 7.0 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=8.4 Hz), 7.28 (dd, 1H, J=4.2, 7.0 Hz), 7.08 (t, 1H, J=73.6 Hz), 5.24 (s, 1H), 3.50-3.47 (m, 4H), 2.57 (t, 2H, J=7.2 Hz), 2.49-2.39 (m, 6H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  3. waitup to 95.0% in 1 min
  4. customin 1 min
  5. waitdown to 27.0% in 2 min)

Sources & evidence

ORD record
ord-0d53edb78b5c47c9a58a94536674b468
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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