Water → HCID 86758642, compound

Reaction equation

[C:1]([C:4]1[CH:5]=[C:6]([N:11]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:12]2)[CH:7]=[CH:8][C:9]=1Cl)([OH:3])=O.[C:25]12([CH2:35][NH2:36])[CH2:34][CH:29]3[CH2:30][CH:31]([CH2:33][CH:27]([CH2:28]3)[CH2:26]1)[CH2:32]2.O.[CH3:38]N(C)C=O>>[CH3:38][C:9]1[CH:8]=[CH:7][C:6]([N:11]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:12]2)=[CH:5][C:4]=1[C:1]([NH:36][CH2:35][C:25]12[CH2:32][CH:31]3[CH2:30][CH:29]([CH2:28][CH:27]([CH2:33]3)[CH2:26]1)[CH2:34]2)=[O:3]

Participants

Reactant 4

HCID 962Water

HCID 6228Dimethylformamide

HCID 86625Tricyclo(3.3.1.13,7)dec-1-ylmethylamine

HCID 86758643HCID 86758643, compound

Product 1

HCID 86758642HCID 86758642, compound

Procedure

A solution of 4-(3-carboxy-4-chlorophenyl)hexahydro-1H-1,4-diazepine-1-carboxylic acid, 1,1-dimethylethyl ester (Example 5b, 0.10 g) and N,N′-carbonyldiimidazole (0.045 g) in dimethylformamide (3 ml) was stirred at room temperature for 2 h. 1-Adamantanemethylamine (0.050 ml) was then added and stirring continued for 14 h. The reaction mixture was poured into water and extracted with ethyl acetate three times. The ethyl acetate layers were combined and washed with 2M hydrochloric acid, 10% aqueous sodium hydroxide and brine, then dried over magnesium sulfate and concentrated under reduced pressure. Purification by chromatography on silica gel, eluting with 20-30% ethyl acetate in iso-hexane, gave the subtitle product as a gum which crystallised on standing.