Methanol → 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid

HRID 1056264Notes

Reaction equation

HRID 1056264 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[NH:12][C:13]([C:21]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:22]=2[N:23]=[C:24]([NH:32][CH2:33][CH:34]([F:36])[F:35])[C:25]([CH3:31])=[N:26]3)=[CH:14][C:15]=1[C:16]([O:18]CC)=[O:17])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO>O1CCOCC1.O>[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[NH:12][C:13]([C:21]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:22]=2[N:23]=[C:24]([NH:32][CH2:33][CH:34]([F:35])[F:36])[C:25]([CH3:31])=[N:26]3)=[CH:14][C:15]=1[C:16]([OH:18])=[O:17])[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 887MethanolHCID 89783848ethyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate

Product 1

HCID 897839472-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A glass microwave reaction vessel was charged with ethyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (950 mg, 1.887 mmol) and LiOH monohydrate (396 mg, 9.43 mmol) in dioxane (8.0 mL) and water (4.00 mL). The reaction mixture was stirred and heated in at 110° C. for 80 min. LC-MS indicated >87% conversion to the desired carboxylic acid m/z (ESI, +ve ion) 476.1 (M+H)+. The reaction mixture was transferred to a 250 mL RBF, using MeOH and concentrated to dryness affording 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid as an orange solid. The orange solid was treated with 4.0 M HCl solution in 1,4-dioxane (11.79 mL, 47.2 mmol) at RT and stirred for 30 min. The reaction mixture was concentrated to give 2-(1-aminoethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (382b) as a red-orange solid. It was used in the subsequent step without further purification assuming quantitative yield. 19F NMR (377 MHz, DMSO-d6) δ ppm −120.68 (1F, s). (m/z (ESI, +ve ion) 376.1 (M+H)+).

Workup

  1. customA glass microwave reaction vessel
  2. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-e0a68792acd24bc092f813234736a78a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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