Water → HCID 118522348, compound

HRID 529817Notes

Reaction equation

HRID 529817 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:38])[CH2:9][N:10]2[CH:14]=[C:13]([NH:15][C:16]([C:18]3[CH:19]=[N:20][N:21]4[CH:26]=[CH:25][CH:24]=[N:23][C:22]=34)=[O:17])[C:12]([C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=3[O:34][CH:35]([F:37])[F:36])=[N:11]2)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48].O>CN(C=O)C.C(OCC)(=O)C>[Cl:33][C:31]1[CH:30]=[CH:29][C:28]([O:34][CH:35]([F:36])[F:37])=[C:27]([C:12]2[C:13]([NH:15][C:16]([C:18]3[CH:19]=[N:20][N:21]4[CH:26]=[CH:25][CH:24]=[N:23][C:22]=34)=[O:17])=[CH:14][N:10]([CH2:9][C:8]([N:5]3[CH2:6][CH2:7][CH:2]([NH:1][CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:3][CH2:4]3)=[O:38])[N:11]=2)[CH:32]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 118522526HCID 118522526, compound

Product 1

HCID 118522348HCID 118522348, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of N-[1-[2-(4-aminopiperidin-1-yl)-2-oxoethyl]-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (126 mg, 0.24 mmol) in DMF (3 mL) was added potassium carbonate (76 mg, 0.55 mmol), ethyl 2-bromoacetate (0.03 mL, 0.27 mmol). The resulting mixture was stirred at 25° C. for 1 h and diluted with 100 mL of ethyl acetate. Water (50 mL) was added. Phases were separated. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. 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 29.3 mg (98%) 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 as a white solid. LCMS (Method 25) [M+H]+=631.2, RT=1.89 min. 1H NMR (400 MHz, CD3OD-d4) δ: (ppm) 8.98 (d, 1H, J=6.8 Hz), 8.53-8.52 (m, 2H), 8.25 (s, 1H), 7.58 (d, 1H, J=2.4 Hz), 7.44 (dd, 1H, J=2.4, 8.8 Hz), 7.29 (d, 1H, J=8.8 Hz), 7.09 (dd, 1H, J=4.4, 6.8 Hz), 6.51 (t, 1H, J=73.6 Hz), 5.20-5.13 (m, 2H), 4.32 (d, 1H, J=13.2 Hz), 4.07 (q, 2H, J=7.2 Hz), 3.91 (d, 1H, J=13.2 Hz), 3.36 (s, 2H), 3.21-3.09 (m, 1H), 2.78-2.68 (m, 2H), 1.94-1.83 (m, 2H), 1.34-1.22 (m, 2H), 1.16 (t, 3H, J=7.2 Hz).

Workup

  1. customPhases were separated
  2. washThe organic phase was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  6. waitGradient: 20% B to 85% B in 10 min
  7. customThis resulted in 29.3 mg (98%) 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 as a white solid

Sources & evidence

ORD record
ord-5439177e744e40f7881a58de7ca3b78b
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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