3-Methoxypropylamine → 4-[({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}amino)sulfonyl]-N-(3-methoxypropyl)benzamide

HRID 655633Notes

Reaction equation

HRID 655633 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]([NH:22][S:23]([C:26]3[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=3)(=[O:25])=[O:24])=[N:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:66][O:67][CH2:68][CH2:69][CH2:70][NH2:71]>CC(N(C)C)=O.C(#N)C>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([NH:11][C:12]2[C:13]([NH:22][S:23]([C:26]3[CH:34]=[CH:33][C:29]([C:30]([NH:71][CH2:70][CH2:69][CH2:68][O:67][CH3:66])=[O:31])=[CH:28][CH:27]=3)(=[O:25])=[O:24])=[N:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1

Participants

8

Reactant 5

HCID 16723-MethoxypropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57625395HCID 57625395, compound

Product 1

HCID 160450124-[({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}amino)sulfonyl]-N-(3-methoxypropyl)benzamideYield 66%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 31374DimethylacetamideSolvent

Procedure

4-[({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}amino)sulfonyl]benzoic acid (100 mg; 0.21 mmol; 1 eq.), EDC-HCl (51.87 mg; 0.27 mmol; 1.3 eq.) and HOBT (36.56 mg; 0.27 mmol; 1.3 eq.) were taken up in DMA (5 ml) then DIEA(106.88 μl; 0.62 mmol; 3 eq.) and 3-methoxypropylamine (21.23 μl; 0.21 mmol; 1 eq.) were added. The solution was stirred at rt for 3 h. The DMA was evaporated and the residue was taken up in DCM. The organic phase was washed with a saturated solution of NaHCO3 then a saturated solution of NH4Cl and brine. It was dried over MgSO4 and concentrated to near dryness. The residue obtained was taken up in ACN and refluxed. After cooling at 4° C., the precipitate was filtered off then washed with ACN to afford 76 mg(66%) of the title compound as a parent. Treatment of the parent (74 mg; 0.13 mmol; 1 eq.) with an aqueous solution of potassium hydroxide (268.30 μl; 0.5 M; 0.13 mmol; 1 eq.) affords 76 mg (96%) of the title compound as a yellow powder. 1H NMR (DMSO-d6) δ 8.77 (s, 1H), 8.49-8.45 (m, 1H), 8.08 (d, J=8.3 Hz, 2H), 7.80 (d, J=8.3 Hz, 2H), 7.41-7.38 (m, 1H), 7.31 (d, J=2.3 Hz, 2H), 7.27-7.24 (m, 1H), 7.17-7.08 (m, 2H), 6.13-6.12 (m, 1H), 3.77 (s, 6H), 3.35-3.31 (m, 2H), 3.28-3.22 (m, 2H), 3.20 (s, 3H), 1.75-1.66 (m, 2H). HPLC (max plot) 97%; Rt 4.17 min. LC/MS: (ES+): 552.4, (ES−): 550.3.

Workup

  1. customThe DMA was evaporated
  2. washThe organic phase was washed with a saturated solution of NaHCO3
  3. dry with materialIt was dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue obtained
  6. temperaturerefluxed
  7. temperatureAfter cooling at 4° C.
  8. filtrationthe precipitate was filtered off
  9. washthen washed with ACN

Sources & evidence

ORD record
ord-64761e4499744549877812bcd22381f7
Source dataset
uspto-grants-2011_12
Patent number
US08071597B2

Reaction notes

Loading…