Benzene → Isopropyl 6-bromo-2-(oxazol-5-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

HRID 2205952Notes

Reaction equation

HRID 2205952 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]3[O:15][CH:14]=[N:13][CH:12]=3)[NH:10][C:4]=2[CH:3]=1.C1C=CC=CC=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].Cl[C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34]>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]3[O:15][CH:14]=[N:13][CH:12]=3)[N:10]([C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34])[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 241BenzeneHCID 7917Isopropyl chloroformateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 867063225-(6-Bromo-1H-pyrrolo[3,2-c]pyridin-2-yl)oxazole

Product 1

HCID 86706336Isopropyl 6-bromo-2-(oxazol-5-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylateYield 74.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(6-Bromo-1H-pyrrolo[3,2-c]pyridin-2-yl)oxazole (Preparation 139, 156 mg 0.59 mmole) was azeotroped with benzene (3 mL) and then dissolved in DMF (1.5 mL). The solution was placed under nitrogen and a solution of sodium hexamethyldisilazide (1M in THF, 0.9 mL, 0.9 mmole) was added and stirred at room temperature for 20 minutes. A solution of isopropyl chloroformate (1M in toluene, 0.9 mL, 0.9 mmole) was added and stirred at room temperature for 4 hours. The reaction was diluted with ethyl acetate (25 mL) and the solution was washed with water (3×10 mL), brine, dried and evaporated to a residue. This was purified using preparative TLC eluting with 3:1 ethyl acetate:cyclohexane. The product band was recovered with acetone to afford the title compound (154 mg, 74%). 1H-NMR (CDCl3, 500 MHz): δ 1.36 (d, J=6.31 Hz, 6H), 5.23 (sept, J=6.31 Hz, 1H), 6.94 (d, J=0.63 Hz, 1H), 7.41 (s, 1H), 8.02 (s, 1H), 8.32 (t, J=0.95 Hz, 1H), 8.69 (d, J=0.95 Hz, 1H).

Workup

  1. stirringstirred at room temperature for 4 hours
  2. washthe solution was washed with water (3×10 mL), brine
  3. customdried
  4. customevaporated to a residue
  5. customThis was purified
  6. washeluting with 3:1 ethyl acetate
  7. customThe product band was recovered with acetone

Sources & evidence

ORD record
ord-81c43213f74e4f299428e5327a858bb2
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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