Diisopropylethylamine → HCID 118522700, compound

HRID 529797Notes

Reaction equation

HRID 529797 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.Cl.[N:34]1([CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][CH:45]([C:48]([O:50][CH3:51])=[O:49])[CH2:44][CH2:43]2)[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.CCN(C(C)C)C(C)C.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:31])[F:32])=[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:37]3[CH2:38][CH2:39][N:34]([CH2:40][CH2:41][N:42]4[CH2:43][CH2:44][CH:45]([C:48]([O:50][CH3:51])=[O:49])[CH2:46][CH2:47]4)[CH2:35][CH2:36]3)=[O:28])[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 118522343HCID 118522343, compoundHCID 118522370{3-(5-Chloro-2-difluoromethoxy-phenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}acetic acid

Product 1

HCID 118522700HCID 118522700, 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 methyl 1-[2-(piperazin-1-yl)ethyl]piperidine-4-carboxylate hydrochloride (190 mg, 0.65 mmol), DIEA (126 mg, 0.97 mmol), HATU (148 mg, 0.39 mmol). The resulting solution was stirred at room temperature overnight and concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with 4% MeOH in DCM. The crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005): Column, XBridge Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% FA and MeCN (22.0% up to 31.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 22.0% in 2 min); Detector, UV 254/220 nm. This resulted in 96.5 mg (40%) of the formic acid salt of methyl 1-[2-[4-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperazin-1-yl]ethyl]piperidine-4-carboxylate as a light yellow solid. LCMS (Method 24) [M+H]+=700.2, RT=2.21 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.6, 6.8 Hz), 8.69-8.68 (m, 2H), 8.30 (s, 1H), 7.62 (dd, 1H, J=2.8, 8.8 Hz), 7.55 (d, 1H, J=2.4 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.28 (dd, 1H, J=4.4, 6.8 Hz), 7.08 (t, 1H, J=73.2 Hz), 5.23 (s, 2H), 3.59 (s, 3H), 3.49-3.46 (m, 4H), 2.84-2.81 (m, 2H), 2.54-2.52 (m, 6H), 2.50-2.40 (m, 2H), 2.33-2.27 (m, 1H), 2.04-1.99 (m, 2H), 1.88-1.70 (m, 2H), 1.55-1.50 (m, 2H).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  3. waitmobile phase, water with 0.05% FA and MeCN (22.0% up to 31.0% in 10 min
  4. waitup to 95.0% in 1 min
  5. customin 1 min
  6. waitdown to 22.0% in 2 min)

Sources & evidence

ORD record
ord-8b3e7bb01c384932a5bfc7b40dfec76a
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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