Potassium Carbonate → 2-(7-(Dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)thiazole-4-carboxylic acid

HRID 220360Notes

Reaction equation

HRID 220360 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:34]=[C:35]=[S:36])(=O)[C:27]1C=CC=CC=1.[C:37]([O-])([O-:39])=[O:38].[K+].[K+].BrCC(=O)C(OCC)=O.[OH-].[Na+]>CC(C)=O.ClCCl>[CH:14]1([N:13]([CH:17]2[CH2:19][CH2:18]2)[C:11]([C:9]2[N:8]([CH2:20][CH3:21])[C:6]3=[N:7][C:2]([NH:1][C:35]4[S:36][CH:27]=[C:26]([C:37]([OH:39])=[O:38])[N:34]=4)=[C:3]4[N:24]=[CH:23][N:22]([CH3:25])[C:4]4=[C:5]3[CH:10]=2)=[O:12])[CH2:16][CH2:15]1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 66144Ethyl bromopyruvateHCID 68284Benzoyl isothiocyanateHCID 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 581805152-(7-(Dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)thiazole-4-carboxylic acidYield 79%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

4-Amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (1J, 300 mg, 0.89 mmol) and benzoyl isothiocyanate (0.16 ml, 1.15 mmol) in acetone (4 ml) were stirred at rt for 1.5 h. The solvent was removed in vacuo and the residue taken up in EtOH (6 ml). K2CO3 (172 mg, 1.241 mmol) was added and the reaction heated at 60° C. for 3 h. The reaction was cooled to rt and ethyl 3-bromo-2-oxopropanoate (692 mg, 3.55 mmol) was added. The reaction was heated at 70° C. overnight. Upon completion of the cyclization step, 1N NaOH (6.3 ml, 6.30 mmol) was added to the reaction mixture and heated at 60° C. for 4 h. The reaction was cooled to room temperature and the solvent removed in vacuo. The remaining aqueous solution was acidified to pH 1 and the precipitate removed by vacuum filtration, washing with water, EtOAc, and then dichloromethane to afford 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-4-ylamino)thiazole-4-carboxylic acid (325 mg, 79% yield) as brown solid.

Workup

  1. customThe solvent was removed in vacuo
  2. temperatureThe reaction was cooled to rt
  3. temperatureThe reaction was heated at 70° C. overnight
  4. temperatureheated at 60° C. for 4 h
  5. temperatureThe reaction was cooled to room temperature
  6. customthe solvent removed in vacuo
  7. customthe precipitate removed by vacuum filtration
  8. washwashing with water, EtOAc

Sources & evidence

ORD record
ord-3a1773c48e9e407dad8d1fb792e88264
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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