Acetyl isothiocyanate → 4-(3-Acetylthioureido)-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 220413Notes

Reaction equation

HRID 220413 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:20][CH3:21])[C:9]([C:11]([N:13]([CH:17]3[CH2:19][CH2:18]3)[CH:14]3[CH2:16][CH2:15]3)=[O:12])=[CH:10][C:5]2=[C:4]2[N:22]([CH3:25])[CH:23]=[N:24][C:3]=12.[C:26]([N:29]=[C:30]=[S:31])(=[O:28])[CH3:27]>CC(C)=O>[C:26]([NH:29][C:30](=[S:31])[NH:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:20][CH3:21])[C:9]([C:11]([N:13]([CH:17]3[CH2:19][CH2:18]3)[CH:14]3[CH2:16][CH2:15]3)=[O:12])=[CH:10][C:5]2=[C:4]2[N:22]([CH3:25])[CH:23]=[N:24][C:3]=12)(=[O:28])[CH3:27]

Participants

4

Reactant 2

HCID 128851Acetyl isothiocyanate2×HCID 581805034-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 581805114-(3-Acetylthioureido)-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 43.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 4-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 60 mg, 0.177 mmol) in acetone (1.182 mL) was added acetyl isothiocyanate (0.020 mL, 0.230 mmol). The reaction mixture was stirred at room temperature for 6 h. LC/MS showed still half of the starting material left. Another 0.5 equivalent of acetyl isothiocyanate was added and the reaction mixture was heated at 35° C. overnight. Solvent was evaporated and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 2-8% methanol/dichloromethane). 4-(3-Acetylthioureido)-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (34 mg, 43.6% yield) was obtained as a yellow solid.

Workup

  1. waitleft
  2. temperaturethe reaction mixture was heated at 35° C. overnight
  3. customSolvent was evaporated
  4. customthe crude product was purified by flash chromatography on silica gel using
  5. washan automated ISCO system (24 g column, eluting with 2-8% methanol/dichloromethane)

Sources & evidence

ORD record
ord-c38bec6fc914417a81bd36fbd97ab154
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

Loading…