Hydrochloric Acid → HCID 118522688, compound

HRID 529853Notes

Reaction equation

HRID 529853 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:44][CH:45]([F:47])[F:46])=[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]3[N:27]=[N:28][N:29]([CH:31]4[CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33][CH2:32]4)[CH:30]=3)[N:9]=2)[CH:7]=1.Cl.C(#N)C.O>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:44][CH:45]([F:47])[F:46])=[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]3[N:27]=[N:28][N:29]([CH:31]4[CH2:32][CH2:33][NH:34][CH2:35][CH2:36]4)[CH:30]=3)[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 18373917Acetonitrile--water (1/1)2×HCID 118522741HCID 118522741, compound

Product 1

HCID 118522688HCID 118522688, compoundYield 2.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl 4-[4-([3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]methyl)-1H-1,2,3-triazol-1-yl]piperidine-1-carboxylate (1.98 g, 2.96 mmol) in methanol (30 mL) was added concentrated HCl aqueous solution (15 mL). The resulting solution was stirred for 5 h at room temperature. The resulting mixture was concentrated under vacuum. This resulted in 1.85 g crude product, which was sufficient for next step without further purification. A small portion was purified for characterization and biological submission. The crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ACN/H2O (10 mmol NH4HCO3)=18% increasing to ACN/H2O (10 mmol NH4HCO3)=49% within 9 min; Detector, UV 254 nm. 42.1 mg product was obtained. This resulted in 42.0 mg of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[[1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl]methyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 36) [M+H]+=569.2, RT=2.59 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.69 (s, 1H), 9.34 (d, 1H, J=6.4 Hz), 8.68-8.64 (m, 2H), 8.40 (s, 1H), 8.22 (s, 1H), 7.67-7.61 (m, 2H), 7.45 (d, 1H, J=8.4 Hz), 7.28 (dd, 1H, J=4.2, 7.0 Hz), 7.06 (t, 1H, J=73.4 Hz), 5.49 (s, 2H), 4.58-4.51 (m, 1H), 3.05-3.02 (m, 2H), 2.62-2.57 (m, 1H), 2.30-2.25 (br, 1H), 2.01-1.98 (m, 2H), 1.87-1.73 (m, 2H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThis resulted in 1.85 g crude product, which
  3. customwas sufficient for next step without further purification
  4. customA small portion was purified for characterization and biological submission
  5. customThe crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)

Sources & evidence

ORD record
ord-f246782d61a2427f96e10ab7da50446e
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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