Sodium hydride → N,N-dicyclopropyl-6-ethyl-4-(5-fluorobenzo[d]thiazol-2-ylamino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 220376Notes

Reaction equation

HRID 220376 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.[H-].[Na+].[F:28][C:29]1[CH:30]=[CH:31][C:32]2[S:36][C:35](S(C)=O)=[N:34][C:33]=2[CH:40]=1>CN(C=O)C.C(OCC)(=O)C>[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][C:32]5[CH:31]=[CH:30][C:29]([F:28])=[CH:40][C:33]=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 3

HCID 24758Sodium hydrideHCID 581805034-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideHCID 581806265-Fluoro-2-(methylsulfinyl)benzo[d]thiazole

Product 1

HCID 58180636N,N-dicyclopropyl-6-ethyl-4-(5-fluorobenzo[d]thiazol-2-ylamino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 17.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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, 50 mg, 0.148 mmol) in DMF (1.5 mL) was added sodium hydride (17.73 mg, 0.443 mmol). After 20 min, 5-fluoro-2-(methylsulfinyl)benzo[d]thiazole (example 40B, 95 mg, 0.443 mmol) was added in one portion. The reaction mixture was stirred at room temperature. The reaction mixture was diluted with ethyl acetate and quenched with water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with 10% lithium chloride solution (2×), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by flash chromatography using an Isco 12 g column eluting with 0-5% MeOH/CH2Cl2 to provide N,N-dicyclopropyl-6-ethyl-4-(5-fluorobenzo[d]thiazol-2-ylamino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (13 mg, 17.07% yield).

Workup

  1. customquenched with water
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with 10% lithium chloride solution (2×)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by flash chromatography
  8. washeluting with 0-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-29a5cd76404442cf95e2f67e3cee0e23
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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