Water → 1-[1-(1-amino-3,4-dihydroisoquinolin-7-yl)-3-t-butyl-1H-pyrazol-5-yl]-3-(2,3-dichlorophenyl)urea

HRID 1696517Notes

Reaction equation

HRID 1696517 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=2[Cl:21])=[O:12])[N:7]([C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][CH2:27][NH:28][C:29]3=S)=[CH:24][CH:23]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].O.[NH3:34].O1CCOCC1>>[NH2:34][C:29]1[C:30]2[C:25](=[CH:24][CH:23]=[C:22]([N:7]3[C:8]([NH:10][C:11]([NH:13][C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=4[Cl:21])=[O:12])=[CH:9][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[N:6]3)[CH:31]=2)[CH2:26][CH2:27][N:28]=1

Participants

4

Reactant 3

HCID 962WaterHCID 66648793Ammonia dioxaneHCID 866200871-[3-t-butyl-1-(1-thioxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazol-5-yl]-3-(2,3-dichlorophenyl)urea

Product 1

HCID 588516271-[1-(1-amino-3,4-dihydroisoquinolin-7-yl)-3-t-butyl-1H-pyrazol-5-yl]-3-(2,3-dichlorophenyl)ureaYield 15%

Conditions

Temperature
80 °C

Procedure

1-[3-t-Butyl-1-(1-thioxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazol-5-yl]-3-(2,3-dichlorophenyl)urea (0.170 g, 0.348 mmol) was dissolved in 0.5M NH3/dioxane (30 mL). Mercuric chloride (0.142 g, 0.522 mmol) was added and the mixture was stirred at 80° C. After 18 h, H2O (2 mL) was added. The mixture was stirred for 30 min and filtered through a pad of Celite®. The solvent was removed under vacuum and the residue was purified by reverse-phase chromatography to yield 1-[1-(1-amino-3,4-dihydroisoquinolin-7-yl)-3-t-butyl-1 H-pyrazol-5-yl]-3-(2,3-dichlorophenyl)urea (25 mg, 15% yield). 1H NMR (400 MHz, CD3OD): □ 8.14 (d, J=2.0 Hz, 1H), 7.99-7.96 (m, 1H), 7.84 (dd, J=8.0, and 2.0 Hz, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.23-7.21 (m, 2H), 6.46 (s, 1H), 3.62 (t, J=6.8 Hz, 2H), 3.14 (t, J=6.8 Hz, 2H), 1.35 (s, 9H); MS (ESI) m/z: 471.3 (M+H+).

Workup

  1. stirringThe mixture was stirred for 30 min
  2. filtrationfiltered through a pad of Celite®
  3. customThe solvent was removed under vacuum
  4. customthe residue was purified by reverse-phase chromatography

Sources & evidence

ORD record
ord-3aace8c292f84814bd75546ef8befecd
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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