Water → HCID 178484279, compound

HRID 526779Notes

Reaction equation

HRID 526779 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[C:17]([CH2:18][N:19]([CH3:31])[CH2:20][CH2:21][N:22](C)[C:23](=O)OC(C)(C)C)=[CH:16][N:15](C3CCCCO3)[N:14]=2)[CH:5]=[C:6]([Cl:12])[C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].O.[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40].CC#N>Cl>[F:42][C:41]([F:44])([F:43])[C:39]([OH:45])=[O:40].[F:42][C:41]([F:44])([F:43])[C:39]([OH:45])=[O:40].[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[C:17]([CH2:18][N:19]([CH3:31])[CH2:20][CH2:21][NH:22][CH3:23])=[CH:16][NH:15][N:14]=2)[CH:5]=[C:6]([Cl:12])[C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 962WaterHCID 6342Acetonitrile2×HCID 6422Trifluoroacetic acidHCID 117665955HCID 117665955, compound

Product 1

HCID 178484279HCID 178484279, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of tert-butyl N-[2-[([3-[3,5-dichloro-4-(propan-2-yloxy)phenyl]-1-(oxan-2-yl)-1H-pyrazol-4-yl]methyl)(methyl)amino]ethyl]-N-methylcarbamate (210 mg, 0.38 mmol, 1.00 equiv) in 3N hydrochloric acid (20 mL) was stirred at 40° C. overnight. The resulting solution was washed with 3×10 mL of dichloromethane. The aqueous layer was concentrated under vacuum and the crude product was purified by Prep-HPLC with the following conditions (2#-Waters 2767-2(HPLC-08)): Column, Xbridge Shield RP 18, 5 um, 19*150 mm; mobile phase, water with 50 mmol CF3COOH and CH3CN (10.0% CH3CN up to 28.0% in 2 min, up to 46.0% in 10 min, up to 100.0% in 1 min, down to 10.0% in 1 min); Detector, UV 254 nm to yield 106.4 mg (47%) of ([3-[3,5-dichloro-4-(propan-2-yloxy)phenyl]-1H-pyrazol-4-yl]methyl)(methyl)[2-(methylamino)ethyl]amine bis(trifluoroacetic acid) salt as a yellow oil. 1H-NMR (300 MHz, D2O): δ 7.94 (s, 1H), 7.56 (s, 2H), 4.89-4.52 (m, 1H), 4.44 (s, 2H), 3.29 (s, 4H), 2.62 (d, J=4.5 Hz, 6H), 1.32 (d, J=6.3 Hz, 6H) ppm. LCMS (method D, ESI): RT=1.28 min, m/z=371.0 [M+H]+.

Workup

  1. washThe resulting solution was washed with 3×10 mL of dichloromethane
  2. concentrationThe aqueous layer was concentrated under vacuum
  3. customthe crude product was purified by Prep-HPLC with the following conditions (2#-Waters 2767-2(HPLC-08))
  4. waitup to 100.0% in 1 min
  5. waitdown to 10.0% in 1 min)

Sources & evidence

ORD record
ord-9c5e974d205c435393a99d0d8ee7f057
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

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