Ammonia → (r/s)-3-(Tert-butoxycarbonyl)amino-1-(1-amino-4-chloro-5-isoquinolinesulfonyl)-pyrrolidine

HRID 1436049Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19]([Cl:28])=[CH:20][N:21]=[C:22](Cl)[C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[NH3:35]>CN1CCN(C)C1=O.[Cl-].[Na+].O>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19]([Cl:28])=[CH:20][N:21]=[C:22]([NH2:35])[C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of Intermediate 26 (0.20 g), and potassium carbonate (0.31 g) in 1,3-dimethyl-2-imidazolidinone (3 ml, Tokyo Kasei Kogyo) is added with 25% aqueous ammonia (2 ml), and the mixture is stirred at 80° C. for 24 hours in a sealed tube. The reaction mixture is added with saturated brine (30 ml), and extracted 3 times with chloroform (30 ml for each time). The combined organic layer is washed twice with saturated brine (50 ml for each time), and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel chromatography (chloroform:methanol=9:1) to obtain the title compound (64.4 mg (predictive yield)).

Workup

extractionextracted 3 times with chloroform (30 ml for each time)
washThe combined organic layer is washed twice with saturated brine (50 ml for each time), and
dry with materialdried over anhydrous magnesium sulfate
customThe solvent is evaporated under reduced pressure
customthe residue is purified by silica gel chromatography (chloroform:methanol=9:1)

Sources & evidence

ORD record: ord-cdeff63ba2e94216868c9acc8f1098ae
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618984B2

Reaction notes

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