Diisopropylethylamine → HCID 68470489, compound

HRID 1929307Notes

Reaction equation

HRID 1929307 reaction equation
[NH2:1][CH:2]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][N:4]([CH3:15])[C:3]1=[O:16].[C:17]([O:21][C:22]([NH:24][C@H:25]([C:27](O)=[O:28])[CH3:26])=[O:23])([CH3:20])([CH3:19])[CH3:18].O.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>O.ClCCl>[C:17]([O:21][C:22](=[O:23])[NH:24][C@H:25]([C:27](=[O:28])[NH:1][CH:2]1[CH:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:5][N:4]([CH3:15])[C:3]1=[O:16])[CH3:26])([CH3:18])([CH3:19])[CH3:20]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 573467493-Amino-1-methyl-5-phenyl-1,3-dihydro-2H-azepin-2-oneHCID 178526939HCID 178526939, compound

Product 1

HCID 68470489HCID 68470489, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

3-Amino-1-methyl-5-phenyl-1,3-dihydro-azepin-2-one (330 g, 1.54 mol) is combined with dichloromethane (3 L), N-(tert-butoxycarbonyl)-L-alanine (291.4 g, 1.54 mol), and hydroxybenzotriazole hydrate (259.5 g, 1.617 mol). The solution is cooled to about 10° C. To this solution is added diisopropylethylamine (335.4 mL, 1.925 mol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (310.1 g, 1.617 mol) and the contents are allowed to gradually warm to room temperature. After 3.5 hours, the reaction contents are poured into water (1000 mL) and the layers are allowed to separate. The organic layer is further washed with water (1000 mL), 0.1 N HCl (1000 mL), saturated NaHCO3 solution (1000 mL) and finally saturated aqueous sodium chloride solution. The dichloromethane layer is dried over Na2SO4, filtered, and concentrated via rotary evaporation to provide the title compound (about 574 g, 97%) as a tan foam. The material is of sufficient purity to use directly in the next step.

Workup

  1. temperatureto gradually warm to room temperature
  2. customthe reaction contents
  3. customto separate
  4. washThe organic layer is further washed with water (1000 mL), 0.1 N HCl (1000 mL), saturated NaHCO3 solution (1000 mL) and finally saturated aqueous sodium chloride solution
  5. dry with materialThe dichloromethane layer is dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-85745c656adc4f738dabd64eda702fee
Source dataset
uspto-grants-2012_05
Patent number
US08188069B2

Reaction notes

Loading…