Hydrochloric Acid → 5-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylic acid

HRID 1056290Notes

Reaction equation

[F:1][C:2]1[C:3]([C:18]2[NH:22][C:21]([CH3:23])=[C:20]([C:24]([O:26]CC)=[O:25])[CH:19]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([NH:13][C:14]1([CH3:17])[CH2:16][CH2:15]1)=[N:5]2.Cl>O.O1CCOCC1>[F:1][C:2]1[C:3]([C:18]2[NH:22][C:21]([CH3:23])=[C:20]([C:24]([OH:26])=[O:25])[CH:19]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([NH:13][C:14]1([CH3:17])[CH2:15][CH2:16]1)=[N:5]2

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of ethyl 5-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylate (417b) (0.555 g, 1.451 mmol), LiOH monohydrate (Sigma Aldrich, 365 mg, 8.71 mmol) in water (9 mL) and dioxane (18.00 mL) was heated to 80° C. overnight. Reaction mixture was then heated to 105° C. for an additional 4 h. Mixture was cooled back to RT and quenched with 4 M HCl in 1,4-dioxane (Sigma Aldrich, 2.177 mL, 8.71 mmol). Volatile solvents were removed by rotovap. The residue was loaded onto a silica gel samplet. Purification by Biotage (0-100% EtOAc/hexanes) produced 5-(6-fluoro-2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylic acid (417c) (78 mg, 0.220 mmol, 15% yield). m/z (ESI, +ve) 355.0 (M+H).

Workup

customReaction mixture
temperaturewas then heated to 105° C. for an additional 4 h
temperatureMixture was cooled back to RT
customVolatile solvents were removed by rotovap
customPurification by Biotage (0-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-f343729ebec3409a9db498b144eec9d4
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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