Triethylamine → (3R,4S,5S,6S)-N-(1-Carbamoylethyl)-5-(5-isopropyl-2-methoxybenzylamino)-6-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-carboxamide

HRID 865994Notes

Reaction equation

HRID 865994 reaction equation
Cl.Cl.[CH:3]([C:6]1[CH:7]=[CH:8][C:9]([O:38][CH3:39])=[C:10]([CH:37]=1)[CH2:11][NH:12][C@@H:13]1[C@H:18]([CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:17]2[CH2:32][CH2:33][C@H:14]1[C@@H:15]([C:34](O)=[O:35])[CH2:16]2)([CH3:5])[CH3:4].Br.[NH2:41][C@H:42]([C:44]([NH2:46])=[O:45])[CH3:43].C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[C:44]([CH:42]([NH:41][C:34]([C@@H:15]1[C@@H:14]2[CH2:33][CH2:32][N:17]([C@@H:18]([CH:19]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C@H:13]2[NH:12][CH2:11][C:10]2[CH:37]=[C:6]([CH:3]([CH3:4])[CH3:5])[CH:7]=[CH:8][C:9]=2[O:38][CH3:39])[CH2:16]1)=[O:35])[CH3:43])(=[O:45])[NH2:46]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18632422L-Alaninamide--hydrogen bromide (1/1)HCID 70115624(3R,4S,5S,6S)-5-(5-isopropyl-2-methoxybenzylamino)-6-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-carboxylic acid dihydrochloride

Product 1

HCID 9894241(3R,4S,5S,6S)-N-(1-Carbamoylethyl)-5-(5-isopropyl-2-methoxybenzylamino)-6-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-carboxamideYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (3R,4S ,5S ,6S)-5-(5-isopropyl-2-methoxybenzylamino)-6-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-carboxylic acid dihydrochloride (300 mg, 0.5 mmol), alaninamide hydrobromide (100 mg, 0.6 mmol) and triethylamine (70 mg, 0.7 mmol) in DMF (2 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (160 mg, 0.8 mmol) at 0° C. The mixture was stirred at 0° C. for 30 minutes, then at room temperature for 14 hours. Water and NaHCO3 were added and the mixture was extracted with CH2Cl2. The combined extracts were dried, concentrated and purified by a column chromatography on silica-gel (CH2Cl2 /methanol=10:1) to give a title compound (220 mg, 0.39 mmol, 77%).

Workup

  1. waitat room temperature for 14 hours
  2. extractionthe mixture was extracted with CH2Cl2
  3. customThe combined extracts were dried
  4. concentrationconcentrated
  5. custompurified by a column chromatography on silica-gel (CH2Cl2 /methanol=10:1)

Sources & evidence

ORD record
ord-a1110a829a7f4879b1176bed03dd5924
Source dataset
uspto-grants-1996_10
Patent number
US05569662

Reaction notes

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