Hydrochloric Acid → N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide

HRID 336804

Reaction equation

HRID 336804 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:21]([NH:22][C:23]3[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH3:32])[CH:24]=3)=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C(OC([N:40]1[CH2:43][CH:42]([C:44](O)=[O:45])[CH2:41]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.O1CCOCC1>CC(N(C)C)=O>[CH3:30][O:29][C:27]1[CH:28]=[C:23]([NH:22][C:21]2[C:12]([NH:11][S:8]([C:4]3[CH:3]=[C:2]([NH:1][C:44]([CH:42]4[CH2:43][NH:40][CH2:41]4)=[O:45])[CH:7]=[CH:6][CH:5]=3)(=[O:9])=[O:10])=[N:13][C:14]3[C:19]([N:20]=2)=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:24]=[C:25]([O:31][CH3:32])[CH:26]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574484483-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide

Product 1

HCID 57448472N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Into a 20 mL vial was added 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (0.24 mmol, 1 equiv), prepared using procedures similar to those described in Example 15, DMA (5 mL) and 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (0.336 mmol, 1.4 equiv). Hunig's Base (0.792 mmol, 3.3 equiv) and HATU (0.288 mmol, 1.2 equiv) were added to the vial and the reaction mixture was then stirred at room temperature, overnight. Completion of the reaction was indicated by LCMS. The solvent was removed by rotary evaporation. The crude mixture was carried forward without further purification. The residue was suspended in 5 mL ethyl acetate and chilled in an ice bath. A solution of 4 N HCl in dioxane (3 mL, 5 equiv) was added with stirring. The reaction mixture was then stirred at room temperature overnight. The solid materials were collected by filtration, washed with ethylacetate then purified further by preparative reverse-phase HPLC (ammonium acetate/ACN). A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide was obtained (26 mg, 20%). 1H-NMR (400 MHz, d6-DMSO): 10.26 (s, 1H), 8.81 (s, 1H), 8.25 (t, 1H), 8.14 (s, 1H), 7.74 (d, 1H), 7.69 (d, 1H), 7.41-7.39 (m, 1H), 7.36 (d, 1H), 7.32 (d, 2H), 7.30-7.28 (dd, 1H), 7.14-7.11 (m, 2H), 6.14 (t, 1H), 4.09 (d, 4H), 3.78 (s, 6H); MS (EI) m/z C26H26N6O5S: 535.6 (MH+).

Workup

  1. customprepared
  2. customThe solvent was removed by rotary evaporation
  3. customThe crude mixture was carried forward without further purification
  4. temperaturechilled in an ice bath
  5. stirringwith stirring
  6. stirringThe reaction mixture was then stirred at room temperature overnight
  7. filtrationThe solid materials were collected by filtration
  8. washwashed with ethylacetate
  9. customthen purified further by preparative reverse-phase HPLC (ammonium acetate/ACN)
  10. customequipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column
  11. customthe purification

Sources & evidence

ORD record
ord-7e75f00efd1f46658cbb7a66fa6b040a
Source dataset
uspto-grants-2014_11
Patent number
US08889664B2

Linked notes

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