Water → HCID 178423530, compound

HRID 526750Notes

Reaction equation

HRID 526750 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:13]2[C:14]([CH2:24][N:25]([CH3:36])[CH2:26][CH2:27][NH:28]C(=O)OC(C)(C)C)=[CH:15][N:16](C3CCCCO3)C=2)[CH:5]=[C:6]([CH3:12])[C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].O.C(O)(C(F)(F)F)=O.CC#[N:47]>Cl>[CH:9]([O:8][C:7]1[C:2]([CH3:1])=[CH:3][C:4]([C:13]2[C:14]([CH2:24][N:25]([CH3:36])[CH2:26][CH2:27][NH2:28])=[CH:15][NH:16][N:47]=2)=[CH:5][C:6]=1[CH3:12])([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 962WaterHCID 6342Acetonitrile2×HCID 6422Trifluoroacetic acidHCID 117666078tert-butyl N-[2-[([4-[3,5-dimethyl-4-(propan-2-yloxy)phenyl]-1-(oxan-2-yl)-1H-pyrrol-3-yl]methyl)(methyl)amino]ethyl]carbamate

Product 1

HCID 178423530HCID 178423530, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of tert-butyl N-[2-[([4-[3,5-dimethyl-4-(propan-2-yloxy)phenyl]-1-(oxan-2-yl)-1H-pyrrol-3-yl]methyl)(methyl)amino]ethyl]carbamate (650 mg, 1.30 mmol, 1.00 equiv) in 3N hydrochloric acid (20 mL) was stirred at 60° C. overnight. The reaction 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 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 give 269 mg (38%) of N1-((3-(4-isopropoxy-3,5-dimethylphenyl)-1H-pyrazol-4-yl)methyl)-N1-methylethane-1,2-diamine as a light yellow oil. 1H-NMR (300 MHz, D2O): δ 7.88 (s, 1H), 7.17 (s, 2H), 4.42 (s, 2H), 4.35-4.26 (m, 1H), 3.30-3.10 (m, 4H), 2.57 (s, 3H), 2.23 (s, 6H), 1.23 (d, J=6.3 Hz, 6H) ppm. LCMS (method J, ESI): RT=1.57 min, m/z=317.1 [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-8c8000d606e04f048125c815dd30e3af
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

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