Triphenylphosphine dibromide → tert-Butyl N-[[4-[5-(2-amino-5-bromo-3-pyridyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate

HRID 509535Notes

Reaction equation

HRID 509535 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([NH:10][NH:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:16][CH:15]=2)=O)=[O:9])=[CH:6][C:5]([Br:30])=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.BrP(Br)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>CC#N>[NH2:1][C:2]1[C:7]([C:8]2[O:9][C:12]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[CH:16][CH:15]=3)=[N:11][N:10]=2)=[CH:6][C:5]([Br:30])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 70579Triphenylphosphine dibromide3×HCID 81531Diisopropylethylamine2×HCID 68493219HCID 68493219, compound

Product 1

HCID 67481666tert-Butyl N-[[4-[5-(2-amino-5-bromo-3-pyridyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamateYield 71.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

tert-Butyl N-[[4-[[(2-amino-5-bromo-pyridine-3-carbonyl)amino]carbamoyl]phenyl]methyl]-N-methyl-carbamate (992.3 mg, 2.074 mmol) was dissolved in dry MeCN (15 mL) and cooled in an ice bath under a nitrogen atmosphere. DIPEA (804.2 mg, 1.084 mL, 6.222 mmol) was added via syringe followed by dibromo(triphenyl)phosphorane (1.185 g, 2.696 mmol) portionwise and the reaction allowed to warm to ambient temperature over 15 hours. A further portion of MeCN (15 mL) and dibromo(triphenyl)phosphorane (437.7 mg, 1.037 mmol) were added and the reaction mixture stirred at ambient temperature for a 10 minutes. The precipitate was isolated by filtration and the filtrate concentrated in vacuo. The filtrate was re-dissolved in MeCN (15 mL) and cooled to 0° C. DIPEA (804.2 mg, 1.084 mL, 6.222 mmol) was added followed by dibromo(triphenyl)phosphorane (437.7 mg, 1.037 mmol) and the reaction mixture stirred at 0° C. for 30 minutes. The reaction mixture was concentrated in vacuo and the resultant residue purified by column chromatography (ISCO Companion™, 40 g column, 0-50% EtOAc/Petroleum ether) and the product containing fractions concentrated in vacuo. The residue was combined with the previously obtained precipitate to give the sub-title product as a white solid (682 mg, 63% Yield corrected for residual OPPh3). 1H NMR (400.0 MHz, DMSO) δ 1.39-1.46 (d, 9H), 4.48 (d, J=10.5 Hz, 2H), 7.46 (d, J=8.1 Hz, 2H), 8.22 (d, J=8.2 Hz, 2H), 8.32 (d, J=2.4 Hz, 1H) and 8.49 (d, J=2.4 Hz, 1H) ppm; MS (ES+) 462.1.

Workup

  1. temperaturecooled in an ice bath under a nitrogen atmosphere
  2. customThe precipitate was isolated by filtration
  3. concentrationthe filtrate concentrated in vacuo
  4. dissolutionThe filtrate was re-dissolved in MeCN (15 mL)
  5. temperaturecooled to 0° C
  6. stirringthe reaction mixture stirred at 0° C. for 30 minutes
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. customthe resultant residue purified by column chromatography (ISCO Companion™, 40 g column, 0-50% EtOAc/Petroleum ether)
  9. additionthe product containing fractions
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7df0e41e7d5f436dadd1d2d7a7aad0a5
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

Loading…