Diisopropylethylamine → HCID 118522548, compound

HRID 529826Notes

Reaction equation

HRID 529826 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](O)=[O:27])[N:9]=2)[CH:7]=1.CCN(C(C)C)C(C)C.[CH:42]1([CH2:45][N:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)[CH2:44][CH2:43]1.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]([N:49]3[CH2:50][CH2:51][N:46]([CH2:45][CH:42]4[CH2:44][CH2:43]4)[CH2:47][CH2:48]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9658751-(Cyclopropylmethyl)piperazineHCID 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 118522548HCID 118522548, 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 (100 mg) in DMF (10 mL) was added DIEA (83 mg, 0.64 mmol), 1-(cyclopropylmethyl)piperazine (60.6 mg, 0.43 mmol) and HATU. The resulting solution was stirred at room temperature overnight and concentrated under vacuum. The crude product (120 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=24:40 within 14 min; Detector, UV 254 nm. This resulted in 47.6 mg (38%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(cyclopropylmethyl)piperazin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (Method 20) [M+H]+=585.2, RT=2.40 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.5, 6.9 Hz), 8.69-8.67 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.7, 8.7 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), 3.51-3.49 (m, 4H), 2.49-2.41 (m, 4H), 2.23-2.21 (m, 2H), 0.87-0.82 (m, 1H), 0.50-0.44 (m, 2H), 0.13-0.08 (m, 2H).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product (120 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  3. waitmobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=24:40 within 14 min
  4. customThis resulted in 47.6 mg (38%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(cyclopropylmethyl)piperazin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid

Sources & evidence

ORD record
ord-35c34adaec164c5c9464be95ff1aed73
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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