N-bromobutanimide → HCID 90167983, compound

HRID 1471650Notes

Reaction equation

HRID 1471650 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][NH:11][C:6]2=[CH:5][CH:4]=1.C1C(=O)N([Br:25])C(=O)C1.C(N(CC)C(C)C)(C)C.[C:35](=O)([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[O:36]C(C)(C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Br:25][C:10]1[N:11]([C:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:36])[C:6]2[C:7](=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:9]=1[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

7

Reactant 4

HCID 67184N-bromobutanimideHCID 81531DiisopropylethylamineHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) esterHCID 67973754HCID 67973754, compound

Product 1

HCID 90167983HCID 90167983, compoundYield 25.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Ethyl 2-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetate (1.0 g, 4.26 mmol) was dissolved in methylene chloride (40 mL) and cooled to 0° C. with ice-water bath. NBS (760 mg, 4.26 mmol) was added in small portions over 1 hour. The reaction mixture was allowed to stir at 0° C. for two more hours. Then, to the reaction mixture were added N,N-diisopropylethylamine (1.86 mL, 8.52 mmol), di-tert-butyl carbonate (1.86 g, 8.52 mmol) and 4-dimethylaminopyridine (52 mg, 0.42 mmol). The resulting mixture was allowed to stir overnight at ambient temperature. More methylene chloride was added and washed with water and half-brine. The organic layer was separated and dried over MgSO4. The mixture was filtered and the filtrate was concentrated to dryness, and the residue was purified by silica gel chromatography (loading with toluene, eluting with EtOAc/hexanes) then RP HPLC eluting with acetonitrile/water to afford 455 mg of tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-5-methoxy-1H-pyrrolo[3,2-b]pyridine-1-carboxylate and 131 mg of side product. MS (m/z): 415.0 [M+H]+; HPLC retention time 4.68 min (5-99% acetonitrile:water with 0.05% formic acid).

Workup

  1. stirringto stir overnight at ambient temperature
  2. washwashed with water and half-brine
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationThe mixture was filtered
  6. concentrationthe filtrate was concentrated to dryness
  7. customthe residue was purified by silica gel chromatography (loading with toluene, eluting with EtOAc/hexanes)
  8. washRP HPLC eluting with acetonitrile/water

Sources & evidence

ORD record
ord-b003327e3aee456f9c9ce3af2b11720f
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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