C([O:3][C:4]([C:6]1[C:7]([CH3:32])=[C:8](C(OC(C)(C)C)=O)[NH:9][C:10]=1[CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH:16]([OH:24])[CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=O)C.C[Al](C)C>C1(C)C=CC=CC=1>[OH:24][CH:16]([CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[CH2:15][N:14]1[CH2:13][CH2:12][CH2:11][C:10]2[NH:9][CH:8]=[C:7]([CH3:32])[C:6]=2[C:4]1=[O:3]5-[3-(2-hydroxy-3-morpholin-4-yl-propylamino)-propyl]-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 53d (580 mg, 1.28 mmol) was dissolved in 6 ml of toluene under stirring, and trimethyl aluminum in toluene (1.9 ml, 2 mol/L, 3.84 mmol) was added dropwise in an ice-water bath under an argon atmosphere. Upon completion of the addition, the ice-water bath was removed, and the reaction mixture was heated to reflux for 24 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was concentrated under reduced pressure, added with hydrochloric acid solution (20 ml, 6 mol/L) and stirred for 20 minutes at room temperature. The mixture was adjusted to about pH 12 with aqueous sodium hydroxide solution (12 mol/L) in an ice-water bath and extracted with dichloromethane (50 ml×2). The combined organic extracts were concentrated under reduced pressure, purified by silica gel column chromatography to obtain the title compound 5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 53e (300 mg, yield 57.6%) as a white solid.
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