Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → tert-butyl 2-amino-4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-7-oxo-6,7-dihydro-5H-imidazo[1,2-a][1,4]diazepin-8(9H)-yl]carbonyl}amino)propyl]benzoate

HRID 80589Notes

Reaction equation

C([C:5]1[C:6]([NH2:45])=[C:7]([CH:11]=[CH:12][C:13]=1[C@H:14]([NH:17][C:18]([N:20]1[C:26](=[O:27])[C@@H:25]([CH2:28][C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=2[O:36][CH3:37])[CH2:24][NH:23][C:22](=[N:38][CH2:39][CH:40](OC)OC)[CH2:21]1)=[O:19])[CH2:15][CH3:16])[C:8]([OH:10])=[O:9])(C)(C)C.[C:46]1([CH3:56])[CH:51]=CC(S([O-])(=O)=O)=C[CH:47]=1.[NH+]1C=CC=CC=1>O1CCOCC1>[NH2:45][C:6]1[CH:5]=[C:13]([C@H:14]([NH:17][C:18]([N:20]2[C:26](=[O:27])[C@@H:25]([CH2:28][C:29]3[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=3[O:36][CH3:37])[CH2:24][N:23]3[CH:40]=[CH:39][N:38]=[C:22]3[CH2:21]2)=[O:19])[CH2:15][CH3:16])[CH:12]=[CH:11][C:7]=1[C:8]([O:10][C:46]([CH3:56])([CH3:51])[CH3:47])=[O:9]

Participants

Conditions

Temperature: 100 °C

Procedure

The compound 89a crude product obtained at Step (1) (94.2 mg) was dissolved in 1,4-dioxane (4 ml), pyridinium p-toluenesulfonate (5 mg) was added, and the mixture was stirred at 100° C. for 2 hours. The reaction solution was concentrated, then the residue was purified by flash column chromatography (NH2 silica gel, ethyl acetate/hexane=7/3 to 1/0) to obtain tert-butyl 2-amino-4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-7-oxo-6,7-dihydro-5H-imidazo[1,2-a][1,4]diazepin-8(9H)-yl]carbonyl}amino)propyl]benzoate (compound 89b) (33.4 mg).

Workup

concentrationThe reaction solution was concentrated
customthe residue was purified by flash column chromatography (NH2 silica gel, ethyl acetate/hexane=7/3 to 1/0)

Sources & evidence

ORD record: ord-e1ed0537b39c47d8902c3859ad2639ac
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846660B2

Reaction notes

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