Sodium hydride → (Z)-N,N-Dicyclopropyl-4-(4,4-dimethoxy-1-(methylthio)-3-oxobut-1-enylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 1188077Notes

Reaction equation

HRID 1188077 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:9]=[C:8]2[N:10]([CH2:22][CH3:23])[C:11]([C:13]([N:15]([CH:19]3[CH2:21][CH2:20]3)[CH:16]3[CH2:18][CH2:17]3)=[O:14])=[CH:12][C:7]2=[C:6]2[N:24]([CH3:27])[CH:25]=[N:26][C:5]=12.[CH3:28][O:29][CH:30]([O:39][CH3:40])[C:31](=[O:38])[CH:32]=[C:33](SC)[S:34][CH3:35]>CN(C=O)C.C(OCC)(=O)C>[CH:16]1([N:15]([CH:19]2[CH2:21][CH2:20]2)[C:13]([C:11]2[N:10]([CH2:22][CH3:23])[C:8]3=[N:9][C:4]([NH:3]/[C:33](/[S:34][CH3:35])=[CH:32]/[C:31](=[O:38])[CH:30]([O:29][CH3:28])[O:39][CH3:40])=[C:5]4[N:26]=[CH:25][N:24]([CH3:27])[C:6]4=[C:7]3[CH:12]=2)=[O:14])[CH2:18][CH2:17]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 111603891,1-Dimethoxy-4,4-bis(methylsulfanyl)but-3-en-2-oneHCID 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 58180627(Z)-N,N-Dicyclopropyl-4-(4,4-dimethoxy-1-(methylthio)-3-oxobut-1-enylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (142 mg, 3.55 mmol) was added to 4-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 400 mg, 1.182 mmol) in DMF (7 mL) at room temperature and the mixture stirred for 30 min, 1,1-dimethoxy-4,4-bis(methylthio)but-3-en-2-one (394 mg, 1.773 mmol) was added and stirring continued overnight. The reaction mixture was diluted with ethyl acetate and washed with water, 10% lithium chloride and water. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (80 g column, eluting with 2-5% methanol/dichloromethane). (Z)—N,N-Dicyclopropyl-4-(4,4-dimethoxy-1-(methylthio)-3-oxobut-1-enylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (484 mg, 0.944 mmol, 80% yield) was obtained as a yellow solid.

Workup

  1. stirringstirring continued overnight
  2. washwashed with water, 10% lithium chloride and water
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel using
  7. washan automated ISCO system (80 g column, eluting with 2-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-bb064d8d099046a1a8811b34e5c58a5a
Source dataset
uspto-grants-2014_03
Patent number
US08673933B2

Reaction notes

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