(-)-2-Aminobutyric acid → Methyl 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-4-methylthiazole-5-carboxylate

HRID 1188061Notes

Reaction equation

HRID 1188061 reaction equation
Br[CH:2]([C:7](=O)[CH3:8])[C:3]([O:5][CH3:6])=[O:4].N[C@H](C(O)=O)CC.[CH:17]1([N:20]([CH:42]2[CH2:44][CH2:43]2)[C:21]([C:23]2[N:39]([CH2:40][CH3:41])[C:26]3=[N:27][C:28]([NH:35][C:36]([NH2:38])=[S:37])=[C:29]4[N:33]=[CH:32][N:31]([CH3:34])[C:30]4=[C:25]3[CH:24]=2)=[O:22])[CH2:19][CH2:18]1>C(O)C>[CH:42]1([N:20]([CH:17]2[CH2:18][CH2:19]2)[C:21]([C:23]2[N:39]([CH2:40][CH3:41])[C:26]3=[N:27][C:28]([NH:35][C:36]4[S:37][C:2]([C:3]([O:5][CH3:6])=[O:4])=[C:7]([CH3:8])[N:38]=4)=[C:29]4[N:33]=[CH:32][N:31]([CH3:34])[C:30]4=[C:25]3[CH:24]=2)=[O:22])[CH2:43][CH2:44]1

Participants

5

Reactant 3

HCID 80283(-)-2-Aminobutyric acidHCID 13048349Methyl 2-bromo-3-oxobutanoateHCID 58180527N,N-dicyclopropyl-6-ethyl-1-methyl-4-thioureido-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 58180557Methyl 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-4-methylthiazole-5-carboxylateYield 84%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

Methyl 2-bromo-3-oxobutanoate (213 mg, 1.094 mmol, prepared following the procedure described by Abu T. Khan et al. in Tetrahedron Letters 2006, 47, 2751-2754) was added to a suspension of N,N-dicyclopropyl-6-ethyl-1-methyl-4-thioureido-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 2B, 290 mg, 0.730 mmol) in ethanol (5 ml) and the reaction mixture was heated at 65° C. for 2 h. LC/MS shows completion of reaction (reaction remained as suspension all the time). The reaction mixture was concentrated to remove ethanol, and taken up in dichloromethane. The solution was washed with saturated sodium bicarbonate and the aqueous layer was back extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude was purified by flash chromatography using an automated ISCO system (40 g column, eluting with 0-5% methanol/dichloromethane) to afford methyl 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-4-methylthiazole-5-carboxylate (301 mg, 0.610 mmol, 84% yield) as a white solid.

Workup

  1. customcompletion of reaction (
  2. customreaction
  3. concentrationThe reaction mixture was concentrated
  4. customto remove ethanol
  5. washThe solution was washed with saturated sodium bicarbonate
  6. extractionthe aqueous layer was back extracted with dichloromethane
  7. dry with materialThe combined organic layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude was purified by flash chromatography
  11. washan automated ISCO system (40 g column, eluting with 0-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-595c8096a49d4b7396aff6dcfa8edb94
Source dataset
uspto-grants-2014_03
Patent number
US08673933B2

Reaction notes

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