Hydrochloric Acid → (R)-4-(1-Cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-2-(methoxycarbonylamino)butanoic acid

HRID 1481036Notes

Reaction equation

[NH2:1][C@H:2]([CH2:6][CH2:7][NH:8][C:9]([C:11]1[N:12]=[C:13]([C:29]#[N:30])[C:14]2[C:19]([C:20]=1[OH:21])=[CH:18][CH:17]=[C:16]([O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH:15]=2)=[O:10])[C:3]([OH:5])=[O:4].C(N(CC)CC)C.Cl[C:39]([O:41][CH3:42])=[O:40].Cl>C(Cl)Cl.CCOC(C)=O.O>[C:29]([C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[C:16]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:15]=2)[C:20]([OH:21])=[C:11]([C:9]([NH:8][CH2:7][CH2:6][C@@H:2]([NH:1][C:39]([O:41][CH3:42])=[O:40])[C:3]([OH:5])=[O:4])=[O:10])[N:12]=1)#[N:30]

Participants

Conditions

Temperature: 0 °C

Procedure

(R)-2-Amino-4-(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)butanoic acid (15 mg, 0.03 mmol) in CH2Cl2 (1 mL) was cooled to 0° C. To the solution were added triethylamine (0.03 mL, 0.21 mmol) and methyl chloroformate (4 μL, 0.05 mmol). After stirring for 5 minutes at 0° C., H2O (10 mL) and EtOAc (10 mL) were added. To the stirred mixture was added 1 N hydrochloric acid (1 mL). The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-20% MeOH/CH2Cl2 with 0.5% formic acid) to give the title compound in 5 mg. MS: (−) m/z 463.21 (M−1).

Workup

customThe layers were separated
extractionthe aqueous layer was extracted twice with EtOAc
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated
custompurified by flash chromatography (0-20% MeOH/CH2Cl2 with 0.5% formic acid)

Sources & evidence

ORD record: ord-67e9edece4fe43bdaf3746100bd96e78
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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