HCID 118522786, compound → HCID 118522772, compound

HRID 529804Notes

Reaction equation

HRID 529804 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:51][CH:52]([F:54])[F:53])=[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:28]3[CH2:33][CH2:32][CH:31]([C:34]([O:36][CH2:37][CH:38]4[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]4)=[O:35])[CH2:30][CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1>O1CCOCC1.Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:51][CH:52]([F:54])[F:53])=[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:28]3[CH2:33][CH2:32][CH:31]([C:34]([O:36][CH2:37][CH:38]4[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]4)=[O:35])[CH2:30][CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

3

Reactant 1

HCID 118522786HCID 118522786, compound

Product 1

HCID 118522772HCID 118522772, compound

Reagents, catalysts & solvents 1

HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

A solution of [1-[(tert-butoxy)carbonyl]piperidin-4-yl]methyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidine-4-carboxylate (150 mg, 0.19 mmol) and saturated HCl dioxane solution (10 mL) was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of methanol. The resulting mixture was concentrated under vacuum. 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 (30.0% up to 33.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 30.0% in 2 min); Detector, UV 254/220 nm. This resulted in 82.3 mg (59%) of the formic acid salt of piperidin-4-ylmethyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidine-4-carboxylate as a light yellow solid. LCMS (Method 20) [M+H]+=671.3, RT=1.58 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.33 (dd, 1H, J=1.2, 6.9 Hz), 8.68-8.67 (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=4.5, 7.2 Hz), 7.01 (t, 1H, J=73.5), 5.25-5.23 (m, 2H), 4.24-4.19 (m, 1H), 3.93-3.85 (m, 3H), 2.83-2.80 (m, 1H), 2.72-2.64 (m, 3H), 1.92-1.87 (m, 3H), 1.71-1.67 (m, 3H), 1.59-1.48 (m, 1H), 1.44-1.23 (m, 2H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. additionThe resulting solution was diluted with 10 mL of methanol
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. customThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  5. waitup to 95.0% in 1 min
  6. customin 1 min
  7. waitdown to 30.0% in 2 min)

Sources & evidence

ORD record
ord-842d60bb3fe344c585e946f743c5aca6
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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