6-Bromo-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carbonitrile → 2-{[1-Ethyl-1-(hydroxymethyl)propyl]amino}-4,5-dihydronaphtho[1,2-d][1,3]thiazole-7-carbonitrile

HRID 1436071Notes

Reaction equation

HRID 1436071 reaction equation
Br[CH:2]1[CH2:11][CH2:10][C:9]2[CH:8]=[C:7]([C:12]#[N:13])[CH:6]=[CH:5][C:4]=2[C:3]1=O.[CH2:15]([C:17]([NH:22][C:23]([NH2:25])=[S:24])([CH2:20][OH:21])[CH2:18][CH3:19])[CH3:16]>C(O)C.C(OCC)(=O)C>[CH2:15]([C:17]([NH:22][C:23]1[S:24][C:2]2[CH2:11][CH2:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([C:12]#[N:13])[CH:8]=3)[C:3]=2[N:25]=1)([CH2:20][OH:21])[CH2:18][CH3:19])[CH3:16]

Participants

5

Reactant 2

HCID 675113086-Bromo-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carbonitrileHCID 86618580N-[1-ethyl-1-(hydroxymethyl)propyl]thiourea

Product 1

HCID 866186112-{[1-Ethyl-1-(hydroxymethyl)propyl]amino}-4,5-dihydronaphtho[1,2-d][1,3]thiazole-7-carbonitrileYield 55%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Bromo-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carbonitrile (0.23 g, 0.90 mmol) was dissolved in 10 mL of ethanol and N-[1-ethyl-1-(hydroxymethyl)propyl]thiourea (133 mg, 1.32 mmol), prepared in step 5 of example 2, was added and the mixture was heated to reflux for 1 h. The mixture was cooled, diluted with ethyl acetate and washed with H2O, NaHCO3, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (3% acetone/hexane) afforded 2-{[1-ethyl-1-(hydroxymethyl)propyl]amino}-4,5-dihydronaphtho[1,2-d][1,3]thiazole-7-carbonitrile (160 mg, 55%) as a white solid. HRMS: calcd for C18H21N3OS+H+, 328.14781. found (ESI-FTMS, [M+H]1+), 328.14836; Analytical HPLC: purity 93.3% at 210-370 nm, 10.3 min.; 96.4% at 254 nm, 10.3 min.; the Xterra® RP18 column, 3.5μ, 150 ×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1 h
  4. temperatureThe mixture was cooled
  5. washwashed with H2O, NaHCO3, brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b2ca68b3534845c98d0b9973ce3fe4f5
Source dataset
uspto-grants-2009_11
Patent number
US07618989B2

Reaction notes

Loading…