Benzene → HCID 86757898, compound

HRID 278882Notes

Reaction equation

HRID 278882 reaction equation
[NH2:1][CH:2]([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:3][NH:4][CH:5]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:16][CH:15]=1)[C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].N1([NH:39][C:40]([Cl:42])=[O:41])CCCCCC1.C(N(CC)C(C)C)(C)C.[ClH:52].[CH:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>CN(C)C1C=CN=CC=1.C(OCC)(=O)C.C(OCC)C>[ClH:42].[ClH:52].[CH2:21]([O:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][CH:5]([NH:4][CH2:3][CH:2]([NH:1][C:40]([N:39]2[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]2)=[O:41])[CH2:28][CH:29]([CH3:31])[CH3:30])[C:6](=[O:7])[NH:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[CH:19][CH:18]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

9

Reactant 5

HCID 241BenzeneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 22623864HCID 22623864, compoundHCID 22623870HCID 22623870, compound

Product 1

HCID 86757898HCID 86757898, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 746 mg (1.6 mmol) 2-(2-amino-4-methyl-pentylamino)-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide, 0.408 mL (3.1 mmol) hexahydroazepinyl carbamoyl chloride, 20 mg (0.16 mmol) 4-dimethylaminopyridine (Aldrich, Milwaukee, Wis.), 0.818 mL (4.7 mmol) N,N-diisopropylethylamine (Aldrich, Milwaukee, Wis.), in 10 mL of benzene was heated under reflux for 16 hours, cooled to 25° C. and filtered, and the solids washed with benzene. The filtrate was concentrated under reduced pressure, and the residue thus obtained was dissolved in 100 mL ethyl acetate, and washed with 100 mL each saturated NaHCO3 solution and brine, dried over anhydrous magnesium sulfate, then concentrated under reduced pressure to give a pale amber oil that was purified by column chromatography on silica gel with 1:1 ethyl acetate:chloroform as eluant. The clear, colorless oil obtained was dissolved in 10 mL diethyl ether, and treated with diethyl ether that had been saturated with hydrogen chloride gas. The precipitate that formed was collected by filtration, and the solids washed with ethyl acetate and dried. The title compound was obtained as 440 mg off-white solid (77%); mp 51-57° C.

Workup

  1. temperatureunder reflux for 16 hours
  2. filtrationfiltered
  3. washthe solids washed with benzene
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue thus obtained
  6. washwashed with 100 mL each saturated NaHCO3 solution and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto give a pale amber oil that
  10. customwas purified by column chromatography on silica gel with 1:1 ethyl acetate
  11. customThe clear, colorless oil obtained
  12. customThe precipitate that formed
  13. filtrationwas collected by filtration
  14. washthe solids washed with ethyl acetate
  15. customdried

Sources & evidence

ORD record
ord-56cb5bf9fdc04bb0b48134f11e2bb460
Source dataset
uspto-grants-2002_03
Patent number
US06362174B1

Reaction notes

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