Water → HCID 178484280, compound

HRID 2271411Notes

Reaction equation

HRID 2271411 reaction equation
[CH3:1][N:2]([CH2:10][CH2:11][N:12]([CH3:37])[CH2:13][C:14]1[C:15]([CH:25]2[CH2:30][CH2:29][N:28]([C:31](=[O:36])[CH2:32][CH:33]([CH3:35])[CH3:34])[CH2:27][CH2:26]2)=[N:16][N:17](C2CCCCO2)[CH:18]=1)C(=O)OC(C)(C)C.O.CC#N>C(O)C.O1CCOCC1.Cl>[CH3:34][CH:33]([CH3:35])[CH2:32][C:31]([N:28]1[CH2:27][CH2:26][CH:25]([C:15]2[C:14]([CH2:13][N:12]([CH3:37])[CH2:11][CH2:10][NH:2][CH3:1])=[CH:18][NH:17][N:16]=2)[CH2:30][CH2:29]1)=[O:36]

Participants

7

Reactant 3

HCID 962WaterHCID 6342Acetonitrile2×HCID 90462682HCID 90462682, compound

Product 1

HCID 178484280HCID 178484280, compoundYield 25.1%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl methyl(2-(methyl((3-(1-(3-methylbutanoyl)piperidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)amino)ethyl)carbamate (110 mg, 0.21 mmol, 1.00 equiv) in ethanol (2 mL), 1,4-dioxane (4 mL) and 12N hydrochloric acid (2 mL) was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum and the residue was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters)): Column, XBridge Shield RP18 OBD Column, 5 μm, 19×150 mm; mobile phase, water with 10 mmol NH4HCO3 and CH3CN (18% CH3CN up to 58% in 10 min, up to 95% in 1 min, down to 18% in 2 min); Detector, UV 254/220 nm to give 17.7 mg (25%) of 3-methyl-1-(4-(4-((methyl (2-(methylamino)ethyl)amino)methyl)-1H-p yrazol-3-yl)piperidin-1-yl)butan-1-one as a colorless solid. 1H-NMR (300 MHz, D2O): δ 7.53 (s, 1H), 4.50-4.40 (m, 1H), 4.10-4.00 (m, 1H), 3.44 (s, 2H), 3.25-3.10 (m, 1H), 3.09-2.95 (m, 1H), 2.80-2.65 (m, 3H), 2.53-2.43 (m, 2H), 2.40-2.20 (m, 5H), 2.13 (s, 3H), 2.00-1.75 (m, 3H), 1.72-1.43 (m, 2H), 0.88 (d, J=6.8 Hz, 6H) ppm. LCMS (method R, ESI): RT=1.26 min, m/z=336.2 [M+H]+.

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customthe residue was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters))
  3. waitdown to 18% in 2 min)

Sources & evidence

ORD record
ord-e0280dde47f54c35b1cf9f343f26f1fc
Source dataset
uspto-grants-2015_09
Patent number
US09120757B2

Reaction notes

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