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

HRID 383594
Notes
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Reaction equation

HRID 383594 reaction equation
N#N.CCN(CC)CC.[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH2:22][C:23]([OH:25])=O)[CH:15]=[C:16]([O:20][CH3:21])[C:17]=1[O:18][CH3:19].[CH3:26][O:27][C:28]([C:30]1[CH:34]=[C:33]([C:35]2[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][C:36]=2[N+:42]([O-:44])=[O:43])[O:32][C:31]=1[CH3:45])=[O:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:26][O:27][C:28]([C:30]1[CH:34]=[C:33]([C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:23](=[O:25])[CH2:22][C:14]3[CH:15]=[C:16]([O:20][CH3:21])[C:17]([O:18][CH3:19])=[C:12]([O:11][CH3:10])[CH:13]=3)=[CH:37][C:36]=2[N+:42]([O-:44])=[O:43])[O:32][C:31]=1[CH3:45])=[O:29]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 947NitrogenHCID 8471TriethylamineHCID 703723,4,5-Trimethoxyphenylacetic acidHCID 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 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Suspend EDCHCl (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 (58) (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 (59) (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, J1=8.6 Hz, J2=2.0 Hz); 7.93 (br.s, 1 H); 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-4493adfda4d44c42b794de79a737ba07
Source dataset
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08367677B2

Reaction notes

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