Diisopropylethylamine → HCID 59875627, compound

HRID 849856Notes

Reaction equation

HRID 849856 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:16])([CH3:15])/[CH:10]=[CH:11]/[C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:39][N:40]([C:57](=[O:72])[C@H:58]([NH:70][CH3:71])[CH2:59][C:60]1[CH:69]=[CH:68][C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH:61]=1)[C@@H:41]([C:49]1[O:53][C:52]([C:54]([NH2:56])=[O:55])=[N:51][N:50]=1)[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(N(C(C)C)C(C)C)C>ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:16])([CH3:15])/[CH:10]=[CH:11]/[C:12](=[O:14])[N:70]([C@@H:58]([C:57](=[O:72])[N:40]([C@@H:41]([C:49]1[O:53][C:52]([C:54](=[O:55])[NH2:56])=[N:51][N:50]=1)[CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[CH3:39])[CH2:59][C:60]1[CH:69]=[CH:68][C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH:61]=1)[CH3:71])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18318394181645-94-3HCID 54560552HCID 54560552, compound

Product 1

HCID 59875627HCID 59875627, compoundYield 36.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2E)-4-tert-Butoxycarbonylamino-4-methylpent-2-enoic acid (143 mg, 0.62 mmol) was dissolved in dichloromethane (4 ml). 1-Hydroxy-7-azabenzotriazole (85 mg, 0.62 mmol) and subsequently N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (119 mg, 0.62 mmol) were added. The solution was stirred for 15 min at room temp. 5-((1R)-1-(Methyl((2R)-2-methylamino-3-(2-naphthyl)propionyl)amino)-2-phenylethyl)-[1,3,4]oxadiazol-2-carboxylic acid amide (230 mg, 0.52 mmol) was added. The solution was stirred for 5 min and ethyldiisopropylamine (0.11 ml, 0.62 mmol) was given to the reaction mixture. It was stirred for 16 h at room temp., diluted with ethyl acetate (20 ml) and extracted with water (20 ml). The phases were separated. The aqueous phase was extracted with ethyl acetate (2×10 ml). The combined organic layers were washed with a saturated solution of sodium hydrogencarbonate and dried over magnesium sulfate. The crude product was purified by flash-chromatography on silica (40 g) with dichloromethane/ethyl acetate 1:1 to give 126 mg of ((E)-3-(((1R)-1-(((1R)-1-(5-carbamoyl-[1,3,4]oxadiazol-2-yl)-2-phenylethyl)methylcarbamoyl)-2-(2-naphthyl)ethyl)methylcarbamoyl)-1,1-dimethylallyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe solution was stirred for 5 min
  2. stirringIt was stirred for 16 h at room temp.
  3. extractionextracted with water (20 ml)
  4. customThe phases were separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×10 ml)
  6. washThe combined organic layers were washed with a saturated solution of sodium hydrogencarbonate
  7. dry with materialdried over magnesium sulfate
  8. customThe crude product was purified by flash-chromatography on silica (40 g) with dichloromethane/ethyl acetate 1:1

Sources & evidence

ORD record
ord-920231e2c23e4b9aa1056ce4b4362021
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Reaction notes

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