Potassium Carbonate → N,N-dicyclopropyl-6-ethyl-1-methyl-4-(4-(pyridin-2-yl)thiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 1188037Notes

Reaction equation

HRID 1188037 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([N:34]=[C:35]=[S:36])(=O)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].Br.Br[CH2:45][C:46]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=1)=O>CC(C)=O>[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:45]=[C:46]([C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=5)[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

6

Reactant 4

HCID 11430Potassium CarbonateHCID 68284Benzoyl isothiocyanateHCID 27762312-Bromo-1-(2-pyridinyl)-1-ethanone hydrobromideHCID 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 58180582N,N-dicyclopropyl-6-ethyl-1-methyl-4-(4-(pyridin-2-yl)thiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 10%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

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, 70 mg, 0.21 mmol) and benzoyl isothiocyanate (36 μl, 0.27 mmol) in acetone (1 ml) was stirred at room temperature for 1.5 h. The solvent was removed in vacuo, the residue was taken up in EtOH (1.5 ml), and K2CO3 (40 mg, 0.290 mmol) was added. The reaction was heated at 60° C. for 3 h. Upon cooling to room temperature, 2-bromo-1-(pyridin-2-yl)ethanone, hydrobromide (139.4 mg, 0.50 mmol) was added and the reaction heated at 80° C. for 24 h. The reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (0-7% MeOH/dichloromethane). Re-purification by preparative HPLC provided 10.2 mg (10% yield) of N,N-dicyclopropyl-6-ethyl-1-methyl-4-(4-(pyridin-2-yl)thiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide as a brown solid.

Workup

  1. customThe solvent was removed in vacuo
  2. temperatureUpon cooling to room temperature
  3. temperaturethe reaction heated at 80° C. for 24 h
  4. temperatureThe reaction mixture was cooled to room temperature
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (0-7% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-1ee1109a89794072b80c9f61b37e203b
Source dataset
uspto-grants-2014_03
Patent number
US08673933B2

Reaction notes

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