1-Isopropylpiperazine → HCID 118522447, compound

HRID 529825Notes

Reaction equation

HRID 529825 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH:30]([F:32])[F:31])=[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]([OH:28])=O)[N:9]=2)[CH:7]=1.CCN(C(C)C)C(C)C.[CH3:42][CH:43]([N:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)[CH3:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH:30]([F:32])[F:31])=[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](=[O:28])[N:48]3[CH2:49][CH2:50][N:45]([CH:43]([CH3:44])[CH3:42])[CH2:46][CH2:47]3)[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 780131-IsopropylpiperazineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118522370{3-(5-Chloro-2-difluoromethoxy-phenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}acetic acid

Product 1

HCID 118522447HCID 118522447, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of {3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}acetic acid (150 mg, 0.32 mmol) in DMF (10 mL) was added DIEA (126 mg, 0.97 mmol), 1-(propan-2-yl)piperazine (126 mg, 0.98 mmol) and HATU (185 mg, 0.49 mmol). The resulting solution was stirred at room temperature overnight and concentrated under vacuum. The crude product (200 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, C18 silica gel; mobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=40:60 within 14 min; Detector, UV 254 nm. This resulted in 51.6 mg (28%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-[4-(propan-2-yl)piperazin-1-yl]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (Method 20) [M+H]+=573.2, RT=1.80 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.34 (dd, 1H, J=1.2, 6.9 Hz), 8.69-8.67 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.7, 9.0 Hz), 7.55 (d, 1H, J=2.7 Hz), 7.45 (d, 1H, J=8.7 Hz), 7.28 (dd, 1H, J=4.2, 6.9 Hz), 7.02 (t, 1H, J=73.2 Hz), 5.23 (s, 2H), 3.52-3.48 (m, 4H), 2.78-2.65 (m, 1H), 2.46-2.39 (m, 4H), 1.09-0.97 (d, 6H, J=6.6 Hz).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product (200 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  3. waitmobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=40:60 within 14 min
  4. customThis resulted in 51.6 mg (28%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-[4-(propan-2-yl)piperazin-1-yl]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid

Sources & evidence

ORD record
ord-eedacbea476e43fd99aada64c7166e5f
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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