Potassium Hydroxide → HCID 118522835, compound

HRID 529818Notes

Reaction equation

HRID 529818 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][CH:31]([NH: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+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:41][CH:42]([F:43])[F:44])=[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][CH:31]([NH:34][CH2:35][C:36]([OH:38])=[O:37])[CH2:30][CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 118522348HCID 118522348, compound

Product 1

HCID 118522835HCID 118522835, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of ethyl 2-[[1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidin-4-yl]amino]-acetate (200 mg, 0.32 mmol), KOH (100 mg, 1.78 mmol) in methanol (5 mL) was stirred at 25° C. for 12 h. The crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column: Xbridge C18, 19*150 mm, 5 um; Mobile Phase A: Water/0.05% NH4HCO3, Mobile Phase B: ACN; Flow rate: 30 mL/min; Gradient: 20% B to 85% B in 10 min; 254 nm. This resulted in 28.5 mg (15%) of 2-[[1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]-acetyl)piperidin-4-yl]amino]acetic acid as a white solid. LCMS (Method 25) [M+H]+=603.1, RT=1.39 min. 1H NMR (400 MHz, CD3OD-d4) δ: (ppm) 8.98 (dd, 1H, J=1.2, 6.8 Hz), 8.54-8.53 (m, 2H), 8.24 (s, 1H), 7.57 (d, 1H, J=2.4 Hz), 7.45 (dd, 1H, J=2.8, 8.8 Hz), 7.30 (d, 1H, J=8.8 Hz), 7.09 (dd, 1H, J=4.4, 6.8 Hz), 6.70 (t, 1H, J=73.4 Hz), 5.23-5.10 (m, 2H), 4.54 (d, 1H, J=13.2 Hz), 4.05 (d, 1H, J=13.6 Hz), 3.45 (s, 2H), 3.30-3.11 (m, 4H), 2.71-2.65 (m, 1H), 2.11-2.05 (m, 1H), 1.58-1.43 (m, 2H).

Workup

  1. customThe crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  2. waitGradient: 20% B to 85% B in 10 min
  3. customThis resulted in 28.5 mg (15%) of 2-[[1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]-acetyl)piperidin-4-yl]amino]acetic acid as a white solid

Sources & evidence

ORD record
ord-50b9809109e947da94a12a8219660dce
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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