Water → HCID 178484282, compound

HRID 526781Notes

Reaction equation

HRID 526781 reaction equation
[F:1][C:2]1[CH:39]=[CH:38][CH:37]=[CH:36][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([CH2:22][N:23]([CH3:35])[CH2:24][CH2:25][N:26](C)[C:27](=O)OC(C)(C)C)=[N:13][N:14](C3CCCCO3)[CH:15]=2)=[CH:7][CH:6]=1.O.[C:41]([OH:47])([C:43]([F:46])([F:45])[F:44])=[O:42].CC#N>Cl>[F:44][C:43]([F:46])([F:45])[C:41]([OH:47])=[O:42].[F:1][C:2]1[CH:39]=[CH:38][CH:37]=[CH:36][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:12]([CH2:22][N:23]([CH3:35])[CH2:24][CH2:25][NH:26][CH3:27])=[N:13][NH:14][CH:15]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6342Acetonitrile2×HCID 6422Trifluoroacetic acidHCID 117666197HCID 117666197, compound

Product 1

HCID 178484282HCID 178484282, compoundYield 37.9%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of tert-butyl 2-(((4-(4-(2-fluorophenoxy)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)methyl)(methyl)amino)ethyl(methyl)carbamate (160 mg, 0.30 mmol, 1.00 equiv) in 4N hydrochloric acid (10 mL) was stirred at 60° C. for 2 h. The resulting mixture was cooled to room temperature and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (2#-Waters 2767-2(HPLC-08)): Column, XBridge Shield RP 18, 5 μm, 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 give 53.2 mg (31%) of N1-((4-(4-(2-fluorophenoxy)phenyl)-1H-pyrazol-3-yl)methyl)-N1,N2-dimethylethane-1,2-diamine trifluoroacetate as a yellow oil. 1H NMR (300 MHz, D2O): δ 7.89 (s, 1H), 7.40-7.03 (m, 8H), 4.56 (s, 1H), 3.40-3.23 (m, 4H), 2.73 (s, 3H), 2.64 (s, 3H) ppm. LCMS (method H, ESI): RT=1.34 min, m/z=355.1 [M+H]+.

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product was purified by Prep-HPLC with the following conditions (2#-Waters 2767-2(HPLC-08))
  3. waitup to 100.0% in 1 min
  4. waitdown to 10.0% in 1 min)

Sources & evidence

ORD record
ord-4ba23a6f5d5b48cca5face9be6f6c54a
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

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