Diisopropylethylamine → HCID 118522369, compound

HRID 529832Notes

Reaction equation

HRID 529832 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.Cl.[CH3:34][NH:35][C:36](=[O:44])[CH2:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>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:41]3[CH2:40][CH2:39][N:38]([CH2:37][C:36](=[O:44])[NH:35][CH3:34])[CH2:43][CH2:42]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 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 acidHCID 118523274HCID 118523274, compound

Product 1

HCID 118522369HCID 118522369, 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 N-methyl-2-(piperazin-1-yl)acetamide hydrochloride (125 mg, 0.65 mmol), HATU (185 mg, 0.49 mmol), DIEA (126 mg, 0.97 mmol). The resulting solution was stirred at room temperature for 12 h and concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with 8% MeOH in DCM. The crude product (180 mg) was purified by Prep-HPLC with the following conditions (3#-Pre-HPLC-006(Waters)): Column, XSelect CSH Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, Water with 10 mM NH4CO3 and MeCN (26.0% MeCN up to 40.0% in 8 min); Detector, 254/220. This resulted in 73.9 mg (38%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-[4-[(methylcarbamoyl)methyl]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]+=602.2, RT=3.66 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.34 (dd, 1H, J=1.6, 6.8 Hz), 8.69-8.68 (m, 2H), 8.32 (s, 1H), 7.75 (q, 1H, J=4.8 Hz), 7.63 (dd, 1H, J=2.6, 8.6 Hz), 7.56 (d, 1H, J=2.8 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.29 (dd, 1H, J=4.4, 7.2 Hz), 7.08 (t, 1H, J=73.2 Hz), 5.24 (s, 2H), 3.54 (t, 4H, J=5.0 Hz), 2.95 (s, 2H), 2.63 (d, 3H, J=4.8 Hz), 2.48-2.45 (m, 2H), 2.44-2.41 (m, 2H).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product (180 mg) was purified by Prep-HPLC with the following conditions (3#-Pre-HPLC-006(Waters))
  3. waitmobile phase, Water with 10 mM NH4CO3 and MeCN (26.0% MeCN up to 40.0% in 8 min)
  4. customThis resulted in 73.9 mg (38%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-[4-[(methylcarbamoyl)methyl]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-ab49224865df4a67a30465d3811a8df9
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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