Diisopropylethylamine → 2-Chloro-4-[(quinoline-7-carbonyl)-amino]-benzoic acid methyl ester

HRID 2235135Notes

Reaction equation

HRID 2235135 reaction equation
F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C.[N:34]1[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([C:44]([OH:46])=O)[CH:42]=2)[CH:37]=[CH:36][CH:35]=1.[CH3:47][O:48][C:49](=[O:58])[C:50]1[CH:55]=[CH:54][C:53]([NH2:56])=[CH:52][C:51]=1[Cl:57]>O1CCCC1>[CH3:47][O:48][C:49](=[O:58])[C:50]1[CH:55]=[CH:54][C:53]([NH:56][C:44]([C:41]2[CH:42]=[C:43]3[C:38]([CH:37]=[CH:36][CH:35]=[N:34]3)=[CH:39][CH:40]=2)=[O:46])=[CH:52][C:51]=1[Cl:57]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 599475Quinoline-7-carboxylic acidHCID 2733179PyBroP2×HCID 11839197Methyl 4-Amino-2-chlorobenzoate

Product 1

HCID 686984382-Chloro-4-[(quinoline-7-carbonyl)-amino]-benzoic acid methyl esterYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (6.03 g, 12.9 mmol, 1.1 equiv.) and diisopropyl ethyl amine (3.19 g, 12.9 mmol, 1.1 equiv.) were added to a solution of quinoline-7-carboxylic acid (2.03 g, 11.75 mmol) in tetrahydrofuran (100 ml) and the resultant mixture stirred for 10 minutes. 4-Amino-2-chlorobenzoic acid methyl ester (2.40 g, 12.9 mmol, 1.1 equiv.) in tetrahydrofuran (20 ml) was added and the mixture refluxed for 16 hours. Additional Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (1.10 g, 2.36 mmol, 0.2 equiv.) and diisopropyl ethyl amine (0.61 g, 4.7 mmol, 0.4 equiv.) were added and the mixture refluxed for a further 16 hours. The mixture was evaporated then dissolved in isopropanol (100 ml). Water (5 ml) and 60% aqueous perchloric acid (0.5 ml) were added and the mixture was refluxed for 24 hours. The mixture was filtered while hot then left to cool to room temperature whereupon a crystalline solid was formed. The solid was filtered and washed with cold isopropanol (20 ml) and dichloromethane (20 ml) to give 2-chloro-4-[(quinoline-7-carbonyl)-amino]-benzoic acid methyl ester, 1.42 g (35% yield), as a tan solid. LC @215 nm; Rt 1.11: 100%, m/z (ES+): 341 (M+H+.); δH (400 MHz; d6-DMSO) 10.96 (1H, br.s), 9.05 (1H, m), 8.73 (1H, s), 8.49 (1H, d), 8.18-8.10 (3H, m), 7.94 (2H, s), 7.68 (1H, dd), 3.86 (3H, s).

Workup

  1. temperaturethe mixture refluxed for 16 hours
  2. temperaturethe mixture refluxed for a further 16 hours
  3. customThe mixture was evaporated
  4. dissolutionthen dissolved in isopropanol (100 ml)
  5. additionWater (5 ml) and 60% aqueous perchloric acid (0.5 ml) were added
  6. temperaturethe mixture was refluxed for 24 hours
  7. filtrationThe mixture was filtered while hot
  8. waitthen left
  9. customwas formed
  10. filtrationThe solid was filtered
  11. washwashed with cold isopropanol (20 ml) and dichloromethane (20 ml)

Sources & evidence

ORD record
ord-7daefbde3e5e4cf4bb19d296ffb020c1
Source dataset
uspto-grants-2010_05
Patent number
US07713996B2

Reaction notes

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