Benzoyl isothiocyanate → (6,8-Dimethoxy-4-thioureido-isoquinolin-1-ylmethyl)carbamic acid tert-butyl ester

HRID 14647Notes

Reaction equation

HRID 14647 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH3:22])=[CH:16][C:17]=2[O:19][CH3:20])[C:12]([NH2:23])=[CH:11][N:10]=1)([CH3:4])([CH3:3])[CH3:2].C([N:33]=[C:34]=[S:35])(=O)C1C=CC=CC=1>CC(C)=O>[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH3:22])=[CH:16][C:17]=2[O:19][CH3:20])[C:12]([NH:23][C:34]([NH2:33])=[S:35])=[CH:11][N:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 68284Benzoyl isothiocyanateHCID 59341089(4-Amino-6,8-dimethoxy-isoquinolin-1-ylmethyl)carbamic acid tert-butyl ester

Product 1

HCID 59341068(6,8-Dimethoxy-4-thioureido-isoquinolin-1-ylmethyl)carbamic acid tert-butyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

(4-Amino-6,8-dimethoxy-isoquinolin-1-ylmethyl)carbamic acid tert-butyl ester (225 mg, 0.675 mmol) was taken up in 10 mL of dry acetone, and benzoylisothiocyanate (121 mg, 0.742 mmol) was added dropwise. The reaction was stirred at room temperature for 2 h, and was then concentrated to a yellow solid. This solid was triturated with 50% aqueous EtOH, filtered, and suspended in 10% NaOH (5.0 mL). The reaction mixture was placed in an oil bath that was pre-heated to 98° C. for 1 h, (the solid was dissolved in 10 min). The mixture was cooled, acidified to pH 6-7 by 2.0 N aqueous HCl solution, and filtered. The yellow solid was washed with water, and dried in vacuo to give 126 mg (48%) of (6,8-dimethoxy-4-thioureido-isoquinolin-1-ylmethyl)carbamic acid tert-butyl ester. 1H-NMR (CDCl3): δ, 8.34 (s, 1H), 7.60 (s, 1H), 6.78 (d, 1H, J=2.1 Hz), 6.63 (d, 1H, J=1.9 Hz), 5.06 (d, 2H, J=3.7 Hz), 4.00 (s, 3H), 3.96 (s, 3H), 3.65 (s, 2H), 1.51 (s, 9H); MS: calculated for C18H24N4O4S+H 393.0; found: 393.0.

Workup

  1. concentrationwas then concentrated to a yellow solid
  2. customThis solid was triturated with 50% aqueous EtOH
  3. filtrationfiltered
  4. customThe reaction mixture was placed in an oil bath
  5. temperaturethat was pre-heated to 98° C. for 1 h
  6. dissolution(the solid was dissolved in 10 min)
  7. temperatureThe mixture was cooled
  8. filtrationfiltered
  9. washThe yellow solid was washed with water
  10. customdried in vacuo

Sources & evidence

ORD record
ord-011f3089c93444328bcad8afd4664e92
Source dataset
uspto-grants-2010_06
Patent number
US07732446B1

Reaction notes

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