Nitrogen → 2-Methyl-5-{2-nitro-4-[2-(3,4,5-trimethoxy-phenyl)-acetylamino]-phenyl}-furan-3-carboxylic acid methyl ester

HRID 2075927Notes

Reaction equation

HRID 2075927 reaction equation
N#N.CCN=C=NCCCN(C)C.Cl.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH2:27][C:28]([OH:30])=O)[CH:20]=[C:21]([O:25][CH3:26])[C:22]=1[O:23][CH3:24].[CH3:31][O:32][C:33]([C:35]1[CH:39]=[C:38]([C:40]2[CH:45]=[CH:44][C:43]([NH2:46])=[CH:42][C:41]=2[N+:47]([O-:49])=[O:48])[O:37][C:36]=1[CH3:50])=[O:34]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCN(CC)CC>[CH3:31][O:32][C:33]([C:35]1[CH:39]=[C:38]([C:40]2[CH:45]=[CH:44][C:43]([NH:46][C:28](=[O:30])[CH2:27][C:19]3[CH:20]=[C:21]([O:25][CH3:26])[C:22]([O:23][CH3:24])=[C:17]([O:16][CH3:15])[CH:18]=3)=[CH:42][C:41]=2[N+:47]([O-:49])=[O:48])[O:37][C:36]=1[CH3:50])=[O:34]

Participants

8

Reactant 4

HCID 947NitrogenHCID 703723,4,5-Trimethoxyphenylacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 597857135-(4-Amino-2-nitro-phenyl)-2-methyl-furan-3-carboxylic acid methyl ester

Product 1

HCID 597857112-Methyl-5-{2-nitro-4-[2-(3,4,5-trimethoxy-phenyl)-acetylamino]-phenyl}-furan-3-carboxylic acid methyl esterYield 55%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Suspend EDC.HCl (138 mg, 0.72 mmol) and Et3N (101 μL, 0.72) in anhydrous DCM (4.5 mL) and stir the resulting solution for 5 min at rt. Add 2-(3,4,5-Trimethoxy-phenyl)-acetic acid (163 mg, 0.72 mmol) and DMAP (8 mg, 0.07 mmol) and stir the resulting solution for 10 min. Add 5-(4-Amino-2-nitro-phenyl)-2-methyl-furan-3-carboxylic acid methyl ester (40) (100 mg, 0.36 mmol) and stir the reaction solution for 22 h at rt. Quench reaction solution with sat. aqu. NH4Cl and water, separate layers and extract aqu. layer with DCM (3 times). Wash the combined organic layer with water and brine and dry with Na2SO4. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+1) to obtain 2-Methyl-5-{2-nitro-4-[2-(3,4,5-trimethoxy-phenyl)-acetylamino]-phenyl}-furan-3-carboxylic acid methyl ester (41) (96 mg, 55%) as an yellow solid. 1H NMR (400 MHz, CDCl3): 2.55 (s, 3H); 3.65 (s, 2H); 3.79 (s, 3H); 3.81 (s, 6H); 3.82 (s, 3H); 6.50 (s, 2H); 6.77 (s, 1H); 7.53 (d, 1H, J=8.6 Hz); 7.66 (dd, 1H, J=8.6 Hz, J2=2.0 Hz); 7.93 (br.s, 1H); 7.96 (d, 1H, J=2.0 Hz).

Workup

  1. custom(The following reaction
  2. customQuench
  3. customreaction solution with sat. aqu
  4. customNH4Cl and water, separate layers
  5. extractionextract aqu
  6. washWash the combined organic layer with water and brine
  7. dry with materialdry with Na2SO4
  8. customPurify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+1)

Sources & evidence

ORD record
ord-e82e4b3fea3a4c94a761d9bf19777aab
Source dataset
uspto-grants-2011_04
Patent number
US07923473B2

Reaction notes

Loading…