Triethylamine → HCID 10054961, compound

HRID 441183Notes

Reaction equation

HRID 441183 reaction equation
[NH2:1][C:2]1[C:3](=[O:35])[N:4]([CH2:14][C:15]([NH:17][CH:18]([CH:32]([CH3:34])[CH3:33])[CH:19]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[C:20]([F:23])([F:22])[F:21])=[O:16])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.[CH2:36]([N:43]=[C:44]=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(N(CC)CC)C>O1CCCC1.C(OCC)(=O)C.Cl>[Si:25]([O:24][CH:19]([C:20]([F:23])([F:21])[F:22])[CH:18]([NH:17][C:15](=[O:16])[CH2:14][N:4]1[C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:7]=[C:2]([NH:1][C:44]([NH:43][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:45])[C:3]1=[O:35])[CH:32]([CH3:33])[CH3:34])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:27])[CH3:26]

Participants

7

Reactant 3

HCID 8471Triethylamine2×HCID 76639Benzyl isocyanate3×HCID 10391657HCID 10391657, compound

Product 1

HCID 10054961HCID 10054961, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

R=benzylaminocarbonyl: To a solution of 2-(3-amino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide (300 mg) in dry tetrahydrofuran (10 mL) was added benzyl isocyanate (86 mg). After 20 h triethyl amine (65 mg) and benzyl isocyanate (43 mg) were added. After another 18 h the reaction mixture was diluted with ethyl acetate and 10% hydrochloric acid. The organic portion was separated, washed with 10% hydrochloric acid and brine, and evaporated to give a crude oil. The reaction was found to be incomplete. To a solution of the recovered oil in dry tetrahydrofuran (6 mL) was added triethyl amine (80 mg) and benzyl isocyanate (86 mg). The solution was heated under reflux for 6 h and stirred 18 h. The reaction mixture was diluted with ethyl acetate; washed with saturated aqueous sodium bicarbonate, 10% hydrochloric acid and brine; dried; evaporated; and dried under vacuum to give a crude solid. Purification by chromatography, eluting with ethanol:ethyl acetate:dichloromethane (0.25:3:96.75 ), gave N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)-2-[2-oxo-6-phenyl-3-(3-benzylureido)-1,2-dihydro-1-pyridyl]acetamide (295 mg); TLC: Rf =0.20, ethanol:ethyl acetate:dichloromethane (0.5:4:95.5); MS: m/z=645(M+1).

Workup

  1. customThe organic portion was separated
  2. washwashed with 10% hydrochloric acid and brine
  3. customevaporated
  4. customto give a crude oil
  5. temperatureThe solution was heated
  6. temperatureunder reflux for 6 h
  7. washwashed with saturated aqueous sodium bicarbonate, 10% hydrochloric acid and brine
  8. customdried
  9. customevaporated
  10. customand dried under vacuum
  11. customto give a crude solid
  12. customPurification by chromatography
  13. washeluting with ethanol:ethyl acetate:dichloromethane (0.25:3:96.75 )

Sources & evidence

ORD record
ord-1ac29f4b72a14f4bb9e74ef8541b1796
Source dataset
uspto-grants-1996_05
Patent number
US05521179

Reaction notes

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