2-Aminoquinoline → HCID 66966005, compound

HRID 1514962Notes

Reaction equation

HRID 1514962 reaction equation
[K+].[C:2]([O:6][C:7]([CH2:9][CH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14](/[CH:18]=[CH:19]/[C:20]2[CH:28]=[CH:27][C:23]([C:24]([O-:26])=O)=[CH:22][C:21]=2[N+:29]([O-:31])=[O:30])=[C:13]([Cl:32])[CH:12]=1)=[O:8])([CH3:5])([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:66][C:67]1[CH:76]=[CH:75][C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[N:68]=1>C(Cl)Cl>[C:2]([O:6][C:7](=[O:8])[CH2:9][CH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14](/[CH:18]=[CH:19]/[C:20]2[CH:28]=[CH:27][C:23]([C:24](=[O:26])[NH:66][C:67]3[CH:76]=[CH:75][C:74]4[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=4)[N:68]=3)=[CH:22][C:21]=2[N+:29]([O-:31])=[O:30])=[C:13]([Cl:32])[CH:12]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 113792-AminoquinolineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66966082HCID 66966082, compound

Product 1

HCID 66966005HCID 66966005, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 4-{(E)-2-[4-(2-tert-butoxycarbonylethyl)-2,6-dichlorophenyl]-vinyl}-3-nitrobenzoic acid potassium salt (280 mg, 0.56 mmol) in DCM (6 mL) was added diisopropylethylamine (292 μL, 1.68 mmol) and HATU (320 mg, 0.84 mmol) and the solution was stirred for 30 min. To this was added 2-aminoquinoline (96 mg, 0.66 mmol) and the mixture was stirred 18 h. The reaction mixture was partitioned between ethyl acetate and water, the organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The crude residue was purified by flash chromatography on silica gel, eluting with a gradient of 0-50% ethyl acetate/heptane to obtain 3-(3,5-dichloro-4-{(E)-2-[2-nitro-4-(quinolin-2-ylcarbamoyl)-phenyl]-vinyl}-phenyl)-propionic acid tert-butyl ester as a white solid. MS (m/z) 592.1 (M+1); 1H NMR (DMSO-d6, 400 MHz) δ 11.58 (s, 1H), 8.74 (d, J=1.89 Hz, 1H), 8.43-8.48 (m, 2H), 8.36-8.41 (m, 1H), 8.16 (d, J=8.34 Hz, 1H), 7.99 (d, J=7.33 Hz, 1H), 7.91 (d, J=8.21 Hz, 1H), 7.77 (ddd, J=8.40, 6.95, 1.33 Hz, 1H), 7.56 (dd, J=15.03, 1.14 Hz, 1H), 7.49 (s, 2H), 7.48 (d, J=16.82 Hz, 1H), 7.36 (d, J=16.82 Hz, 1H), 2.85 (t, J=7.26 Hz, 2H), 2.59 (t, J=7.39 Hz, 2H) 1.38 (s, 9H).

Workup

  1. stirringthe mixture was stirred 18 h
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washthe organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography on silica gel
  8. washeluting with a gradient of 0-50% ethyl acetate/heptane

Sources & evidence

ORD record
ord-7ff2244ca01f4c3dba9a488b8b93bf66
Source dataset
uspto-grants-2012_07
Patent number
US08222248B2

Reaction notes

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