2-Aminoquinoline → 2-(2,6-dichloro-4-morpholin-4-yl-phenyl)-1H-indole-6-carboxylic acid quinolin-2-ylamide

HRID 1514952Notes

Reaction equation

HRID 1514952 reaction equation
C[Al](C)C.[N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][C:6]=1[NH2:15].C[O:17][C:18]([C:20]1[CH:28]=[C:27]2[C:23]([CH:24]=[C:25]([C:29]3[C:34]([Cl:35])=[CH:33][C:32]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[CH:31][C:30]=3[Cl:42])[NH:26]2)=[CH:22][CH:21]=1)=O.C[Al](C)C.N1C2C(=CC=CC=2)C=CC=1N>C1(C)C=CC=CC=1>[N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][C:6]=1[NH:15][C:18]([C:20]1[CH:28]=[C:27]2[C:23]([CH:24]=[C:25]([C:29]3[C:30]([Cl:42])=[CH:31][C:32]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[CH:33][C:34]=3[Cl:35])[NH:26]2)=[CH:22][CH:21]=1)=[O:17]

Participants

6

Reactant 4

HCID 113792-AminoquinolineHCID 16682925TrimethylaluminumHCID 669658232-(2,6-dichloro-4-morpholin-4-yl-phenyl)-1H-indole-6-carboxylic acid methyl esterHCID 131729836AlMe3 quinolin-2-ylamine

Product 1

HCID 669655842-(2,6-dichloro-4-morpholin-4-yl-phenyl)-1H-indole-6-carboxylic acid quinolin-2-ylamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

A 2 M solution of AlMe3 in toluene (0.74 mL, 1.48 mmol) was added to a flask charged with dry toluene (6 mL) at 0° C. under N2. In one proportion quinolin-2-ylamine (0.213 g, 1.48 mmol) was added and the mixture was allow to stir for 50 min. The reaction was allowed to warm to ambient temperature over 15 min then a suspension of 2-(2,6-dichloro-4-morpholin-4-yl-phenyl)-1H-indole-6-carboxylic acid methyl ester (0.500 g, 1.23 mmol) in toluene was slowly added to the mixture at 0° C. Upon completing the addition the mixture was heated at 100° C. After 20 h an additional portion of AlMe3/quinolin-2-ylamine solution (0.438 mmol) was added and heating was continued for an additional 3 h. The mixture was allowed to cool to ambient temperature and was concentrated under reduced pressure. The residue was partitioned between EtOAc (70 mL) and 1 N HCl (30 mL) and allowed to stir for 1 h. The resulting precipitate was filtered and dried under reduced pressure to afford 2-(2,6-dichloro-4-morpholin-4-yl-phenyl)-1H-indole-6-carboxylic acid quinolin-2-ylamide as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 11.75 (s, 1H), 11.26 (s, broad, 1H), 8.50 (d, J=8.97 Hz, 1H), 8.34 (d, J=8.97 Hz, 1H), 8.20 (s, 1H), 8.00 (d, J=8.21 Hz, 1H), 7.97 (d, J=8.46 Hz, 1H), 7.76-7.82 (m, 2H), 7.68 (d, J=8.34 Hz, 1H), 7.57 (t, J=7.45 Hz, 1H), 7.17 (s, 2H), 6.54 (d, J=1.77 Hz, 1H), 3.71-3.77 (m, 4H), 3.24-3.32 (m, 4H). MS (m/z) 517.1 (M+1).

Workup

  1. additionwas slowly added to the mixture at 0° C
  2. additionthe addition the mixture
  3. temperaturewas heated at 100° C
  4. temperatureheating
  5. waitwas continued for an additional 3 h
  6. temperatureto cool to ambient temperature
  7. concentrationwas concentrated under reduced pressure
  8. customThe residue was partitioned between EtOAc (70 mL) and 1 N HCl (30 mL)
  9. stirringto stir for 1 h
  10. filtrationThe resulting precipitate was filtered
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-72400ddee2874110b772cf6e8b7d388a
Source dataset
uspto-grants-2012_07
Patent number
US08222248B2

Reaction notes

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