4-Methylmorpholine → Tert-butyl 7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate

HRID 220346Notes

Reaction equation

HRID 220346 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=1[O:36][CH3:37])[C:9]1[N:14]=[C:13]2[N:15]([CH2:21][CH3:22])[C:16]([C:18]([OH:20])=O)=[CH:17][C:12]2=[C:11]2[N:23]([CH3:26])[CH:24]=[N:25][C:10]=12)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH:39]1([NH:42][CH:43]2[CH2:45][CH2:44]2)[CH2:41][CH2:40]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C.CN(C1C=CN=CC=1)C>[CH:39]1([N:42]([CH:43]2[CH2:45][CH2:44]2)[C:18]([C:16]2[N:15]([CH2:21][CH3:22])[C:13]3=[N:14][C:9]([N:8]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=4[O:36][CH3:37])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[C:10]4[N:25]=[CH:24][N:23]([CH3:26])[C:11]4=[C:12]3[CH:17]=2)=[O:20])[CH2:41][CH2:40]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44717154N-cyclopropylcyclopropanamine hydrochlorideHCID 581806154-(tert-Butoxycarbonyl(2,4-dimethoxybenzyl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxylic acid

Product 1

HCID 58180545Tert-butyl 7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl(2,4-dimethoxybenzyl)carbamateYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

To a mixture of 4-(tert-butoxycarbonyl(2,4-dimethoxybenzyl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxylic acid (example 1H, 0.89 g, 1.747 mmol) in acetonitrile (17.47 mL) was added dicyclopropylamine hydrochloride (0.303 g, 2.271 mmol), N-methylmorpholine (0.499 mL, 4.54 mmol), DMAP (0.021 g, 0.175 mmol), and HATU (0.797 g, 2.096 mmol). The reaction mixture was stirred at rt 5 h and heated to 50° C. for 45 min. The reaction was cooled to room temperature. Acetonitrile was removed in vacuo and the residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The aqueous layer was extracted with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude solid was purified by flash chromatography using an Isco 80 g column eluting with 1-4% MeOH/CH2Cl2 to yield tert-butyl 7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate (0.8 g, 78% yield) as an off-white solid.

Workup

  1. temperatureheated to 50° C. for 45 min
  2. temperatureThe reaction was cooled to room temperature
  3. customAcetonitrile was removed in vacuo
  4. customthe residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane
  5. extractionThe aqueous layer was extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude solid was purified by flash chromatography
  10. washeluting with 1-4% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-1ff5e29de3be4b88b60764b1cab9f666
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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