N,N-Dimethylglycine → 2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy-phenylamino)-quinoxalin-2-yl)sulfamoyl)phenyl)acetamide

HRID 1669948Notes

Reaction equation

HRID 1669948 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]([NH2:31])[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.[CH3:32][N:33]([CH3:38])[CH2:34][C:35]([OH:37])=O.CN(C([O:46]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:63][CH2:64][N:65]([CH:69](C)C)[CH:66](C)C>O.[Li+].[Cl-].CN(C=O)C>[CH3:66][N:65]([CH3:69])[CH2:64][C:63]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:8](=[O:10])(=[O:9])[NH:11][C:12]2[C:21]([NH:22][C:23]3[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([NH:31][C:35](=[O:37])[CH2:34][N:33]([CH3:38])[CH3:32])[CH:24]=3)=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)[CH:3]=1)=[O:46]

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574486623-amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide

Product 1

HCID 574484692-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy-phenylamino)-quinoxalin-2-yl)sulfamoyl)phenyl)acetamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 433294Lithium ChlorideSolvent

Conditions

Temperature
90 °C

Procedure

3-Amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (330 mg, 0.76 mmol), DMF (4 mL), N,N,-Dimethylglycine (312 mg, 3.02 mmol), HATU (1.15 g, 3.02 mmol), and 1.29 (mL) (7.56 mmol) DIEA (1.29 mL, 7.56 mmol) were combined and heated to 90° C., followed by heating at 50° C. for over 16 hours. The reaction was allowed to cool, placed into a sep. funnel diluted with water and aqueous LiCl and extracted with EtOAc. The final compound was then purified by prep. HPLC to give 2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy-phenylamino)-quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. 1H NMR (400 MHz, CD3OD) δ 8.45 (t, 1H), 7.93 (t, 1H), 7.85-7.88 (m, 1H), 7.70-7.74 (m, 1H), 7.65-7.68 (m, 1H), 7.58-7.62 (m, 1H), 7.58 (t, 1H), 7.34-7.42 (m, 3H), 7.0 (t, 1H), 4.05 (d, 2H), 3.8 (s, 3H), 2.9-3.0 (d, 12H). MS (EI) m/z for C29H34N8O5S: 607.2 (MH+).

Workup

  1. temperatureby heating at 50° C. for over 16 hours
  2. temperatureto cool
  3. extractionextracted with EtOAc
  4. customThe final compound was then purified by prep

Sources & evidence

ORD record
ord-79890c2de2954b22bd15795349c6c2e9
Source dataset
uspto-grants-2011_08
Patent number
US07989622B2

Reaction notes

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