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

HRID 1612041Notes

Reaction equation

HRID 1612041 reaction equation
[N+]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6]([N:14]([CH2:28][CH2:29][N:30]([CH3:32])[CH3:31])[C:15](=[O:27])[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[CH:18][C:17]=1I)=[CH:7][CH:8]=[N:9]2)([O-])=O.C(Cl)(=O)C(Cl)=O.COC1C=C(C(I)=CC=1OC)C(O)=O.CN(C)CCNC1C2C(=CC=CC=2[N+]([O-])=O)N=CC=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:23][O:22][C:20]1[C:19]([O:24][CH3:25])=[CH:18][C:17]2[C:7]3[C:6](=[C:5]4[CH:4]=[CH:13][CH:12]=[CH:11][C:10]4=[N:9][CH:8]=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 104003814-[[2-(Dimethylamino)ethyl]amino]-5-nitroquinolineHCID 22252597N-(5-Nitroquinolin-4-yl)-N-[2-(N,N-dimethylamino)ethyl]-2-iodo-4,5-dimethoxybenzamide

Product 1

HCID 222526088,9-Dimethoxy-5-[2-(N,N-dimethylamino)ethyl]-5H-dibenzo[c,h]1,6-naphthyridin-6-oneYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Synthesis of N-(quinolin-4-yl)-N-(N,N-dimethylaminoethyl)-2-iodo-5,6-dimethoxybenzamide (8d). Oxalyl chloride (2.1 g, 16.2 mmol) was added to a solution of 3,4-dimethoxy-6-iodobenzoic acid (1.5 g, 4.87 mmol) in anhydrous methylene chloride (40 mL), and the stirred mixture was refluxed for 4 hours. The mixture was then concentrated to dryness under reduced pressure. The acid chloride was redissolved in 40 mL of anhydrous methylene chloride, and this solution was added to a solution of 7d (870 mg, 4.05 mmol) and triethylamine (4.0 g, 40.0 mmol) in methylene chloride (30 mL), and the resulting mixture was stirred at reflux for 2 hours. 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 (3×75 mL). Combined organic extracts were then dried (MgSO4) and evaporated to give 1.45 g of the amide, in 73% yield; 1H NMR (CDCl3) δ 2.23 (s, 6H), 2.63 (m, 2H), 3.07 (s, 3H), 3.68 (s, 3H), 3.93 (m, 1H), 4.62 (m, 1H), 6.26 (s, 1H), 7.00 (s, 1H), 7.44 (d, 1H, J=4.4), 7.69 (m, 2H), 8.11 (m, 2H), 8.75 (d, 1H, J=4.4); 13C NMR (CDCl3) δ 45.6, 47.0, 55.3, 56.0, 56.7, 82.5, 110.2, 121.6, 122.8, 125.8, 127.6, 130.0, 130.5, 130.6, 133.8, 146.9, 148.1, 149.6, 149.8, 150.8, 169.8; IR (CHCl3) 1650;

Workup

  1. temperaturethe stirred mixture was refluxed for 4 hours
  2. concentrationThe mixture was then concentrated to dryness under reduced pressure
  3. dissolutionThe acid chloride was redissolved in 40 mL of anhydrous methylene chloride
  4. temperatureat reflux for 2 hours
  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 (3×75 mL)
  10. dry with materialCombined organic extracts were then dried (MgSO4)
  11. customevaporated

Sources & evidence

ORD record
ord-976644e49bae415894d90412c16818f4
Source dataset
uspto-grants-2006_01
Patent number
US06992089B2

Reaction notes

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