Hydrochloric Acid → HCID 89783657, compound

HRID 1056135Notes

Reaction equation

HRID 1056135 reaction equation
C(OC([NH:8][C:9]1([C:12]2[NH:13][C:14]([C:22]3[C:31]([F:32])=[CH:30][CH:29]=[C:28]4[C:23]=3[N:24]=[C:25]([NH:34][CH:35]3[CH2:37][CH2:36]3)[C:26]([CH3:33])=[N:27]4)=[CH:15][C:16]=2[C:17]([O:19]CC)=[O:18])[CH2:11][CH2:10]1)=O)(C)(C)C.O.[ClH:39].[OH-].[Na+]>O1CCOCC1>[ClH:39].[NH2:8][C:9]1([C:12]2[NH:13][C:14]([C:22]3[C:31]([F:32])=[CH:30][CH:29]=[C:28]4[C:23]=3[N:24]=[C:25]([NH:34][CH:35]3[CH2:37][CH2:36]3)[C:26]([CH3:33])=[N:27]4)=[CH:15][C:16]=2[C:17]([OH:19])=[O:18])[CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 89784446HCID 89784446, compound

Product 1

HCID 89783657HCID 89783657, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (283d) (0.38 g, 0.76 mmol) and LiOH monohydrate (Fluka/Aldrich) (191 mg, 4.56 mmol) in 1,4-Dioxane (7 mL)/Water (3.5 mL). The reaction mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 120° C. for 20 min (100 watts, Powermax feature off). This material was transferred to a 150-mL round-bottomed flask and added 4 M HCl in 1,4-dioxane (Aldrich) until pH 2-3. The mixture was stirred at RT for 2 h. The mixture was neutralized with 5 N NaOH (pH 7), then concentrated under reduced pressure to half of its volume. The residue was diluted with hexanes and placed into a sonicator for 30 sec. The precipitated solid was collected by filtration and washed with hexanes. This gave 2-(1-aminocyclopropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (283e) (0.30 g, 0.718 mmol, 95% yield) as a tan solid. 1H NMR (400 MHz, MeOH-d4) δ ppm 7.86 (m, 1H), 7.44 (m, 1H), 7.34 (s, 1H), 2.68 (s, 3H), 1.56 (m, 4H), 1.14 (d, 2H), 0.91 (s, 2H). m/z (ESI, +ve) 383 (M+H).

Workup

  1. customA glass microwave reaction vessel
  2. customThis material was transferred to a 150-mL round-bottomed flask
  3. stirringThe mixture was stirred at RT for 2 h
  4. concentrationconcentrated under reduced pressure to half of its volume
  5. additionThe residue was diluted with hexanes
  6. filtrationThe precipitated solid was collected by filtration
  7. washwashed with hexanes

Sources & evidence

ORD record
ord-9ace6f24ca9948f388bbf2a5fea4da7b
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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