Triethylamine → 8,9-Dimethoxy-1-nitro-5-[2-(N,N-dimethylamino)ethyl]-5H-dibenzo[c,h][1,6]naphthyridin-6-one

HRID 1612036Notes

Reaction equation

HRID 1612036 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[CH:11][CH:10]=[C:9]2[N:14]([CH2:28][CH2:29][N:30]([CH3:32])[CH3:31])[C:15](=[O:27])[C:16]1[C:21](OC)=[C:20]([O:24][CH3:25])[CH:19]=[CH:18][C:17]=1I)([O-:3])=[O:2].C(Cl)(=O)[C:34](Cl)=[O:35].COC1C=C(C(I)=CC=1OC)C(O)=O.[N+](C1C=CC=C2C=1N=CC=C2NCCN(C)C)([O-])=O.C(N(CC)CC)C>C(Cl)Cl>[CH3:25][O:24][C:20]1[C:19]([O:35][CH3:34])=[CH:18][C:17]2[C:10]3[C:9](=[C:8]4[CH:7]=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[C:13]4=[N:12][CH:11]=3)[N:14]([CH2:28][CH2:29][N:30]([CH3:32])[CH3:31])[C:15](=[O:27])[C:16]=2[CH:21]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27584222-Iodo-4,5-dimethoxybenzoic acidHCID 22252603N'-(8-Nitroquinolin-4-yl)-N,N-dimethylethane-1,2-diamineHCID 69236752N-(8-Nitroquinolin-4-yl)-N-(N,N-dimethylaminoethyl)-2-iodo-5,6-dimethoxybenzamide

Product 1

HCID 100252418,9-Dimethoxy-1-nitro-5-[2-(N,N-dimethylamino)ethyl]-5H-dibenzo[c,h][1,6]naphthyridin-6-oneYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-(8-Nitroquinolin-4-yl)-N-(N,N-dimethylaminoethyl)-2-iodo-5,6-dimethoxybenzamide (8a). Oxalyl chloride (762 mg, 6.0 mmol) was added to a solution of 3,4-dimethoxy-6-iodobenzoic acid (570 mg, 1.85 mmol) in anhydrous methylene chloride (20 mL), and the stirred mixture was refluxed for 3 hours. The mixture was then concentrated to dryness under reduced pressure. The acid chloride was redissolved in 20 mL of anhydrous methylene chloride, and this solution was added to a solution of 7a (400 mg, 1.54 mmol) and triethylamine (1.14 g, 11.3 mmol) in methylene chloride (20 mL), and the resulting mixture was stirred at reflux overnight. The reaction mix was cooled and washed with saturated sodium bicarbonate (3×75 mL), and extracted with 5% aqueous HCl (4×100 mL). The combined aqueous extracts were basified with 30% NaOH and then extracted with chloroform (3×100 mL). Combined organic extracts were then dried (MgSO4) and evaporated to give 722 mg of the amide, in 85% yield; 1H NMR (CDCl3) δ 2.30 (s, 6H), 2.69 (m, 2H), 3.32 (s, 3H), 3.74 (s, 3H), 3.95 (m, 1H), 4.57 (m, 1H), 6.41 (s, 1H), 7.02 (s, 1H), 7.75 (m, 2H), 8.05 (d, 1H, J=6.6), 8.44 (d, 1H, J=8.4), 8.95 (d, 1H, J=4.4); 13C NMR (CDCl3) δ 45.4, 47.3, 55.7, 56.1, 56.5, 82.7, 110.7, 121.9, 123.3, 124.0, 126.1, 126.9, 127.2, 133.1, 140.9, 147.4, 148.4, 149.0, 150.1, 153.0, 169.9; IR (CHCl3) 1362, 1536, 1655.

Workup

  1. temperaturethe stirred mixture was refluxed for 3 hours
  2. concentrationThe mixture was then concentrated to dryness under reduced pressure
  3. dissolutionThe acid chloride was redissolved in 20 mL of anhydrous methylene chloride
  4. temperatureat reflux overnight
  5. additionThe reaction mix
  6. temperaturewas cooled
  7. washwashed with saturated sodium bicarbonate (3×75 mL)
  8. extractionextracted with 5% aqueous HCl (4×100 mL)
  9. extractionextracted with chloroform (3×100 mL)
  10. dry with materialCombined organic extracts were then dried (MgSO4)
  11. customevaporated

Sources & evidence

ORD record
ord-6edd3000e9ad4e6ab3687fb7d5cdb03f
Source dataset
uspto-grants-2006_01
Patent number
US06992089B2

Reaction notes

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