Aniline → HCID 58577913, compound

HRID 473966Notes

Reaction equation

HRID 473966 reaction equation
C(N(C(C)C)C(C)C)C.[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:17][O:18][C:19](=[O:45])[C:20]([CH3:44])([CH3:43])[CH2:21][O:22][C:23]1[N:28]=[CH:27][C:26]([C:29]2[CH:38]=[C:37]3[C:32]([C:33]([C:40](O)=[O:41])=[CH:34][C:35]([CH3:39])=[N:36]3)=[CH:31][CH:30]=2)=[CH:25][CH:24]=1>CN(C)C=O>[CH3:44][C:20]([CH3:43])([CH2:21][O:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]2[CH:38]=[C:37]3[C:32]([C:33]([C:40](=[O:41])[NH:10][C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)=[CH:34][C:35]([CH3:39])=[N:36]3)=[CH:31][CH:30]=2)=[CH:27][N:28]=1)[C:19]([O:18][CH3:17])=[O:45]

Participants

5

Reactant 3

HCID 6115AnilineHCID 81531DiisopropylethylamineHCID 58577826HCID 58577826, compound

Product 1

HCID 58577913HCID 58577913, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Ethyl-N,N-diisopropylamine (64.5 mg, 0.50 mmol) was added at room temperature to a solution of aniline (465.0 mg, 0.50 mmol), 7-(6-(3-methoxy-2,2-dimethyl-3-oxopropoxy)pyridin-3-yl)-2-methylquinoline-4-carboxylic acid B-15 (98.8 mg, 0.25 mmol) and N,N,N′N-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (190.0 mg, 0.50 mmol) in anhydrous N,N-dimethylformamide (5.0 mL) under an atmosphere of nitrogen. The reaction mixture was stirred overnight, then partitioned between methylene chloride (30 mL) and an aqueous solution of pH 7 phosphate buffer (30 mL). The aqueous layer was extracted with methylene chloride (3×30 mL); the combined extracts were successively washed with water (30 mL), brine (30 mL), then dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient) to give methyl 2,2-dimethyl-3-(5-(2-methyl-4-(phenylcarbamoyl)quinolin-7-yl)pyridin-2-yloxy)propanoate B-16 (103.4 mg, Yield=88%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 6H), 2.83 (s, 3H), 3.73 (s, 3H), 4.42 (s, 2H), 6.90 (d, J=8.5 Hz, 1H), 7.26-7.29 (m, 1H), 7.45-7.48 (m, 3H), 7.73-7.77 (m, 2H), 7.88 (s, 1H), 7.95 (q, J=6.0 Hz, 1H), 8.23 (s, 1H), 8.32 (d, J=8.5 Hz, 1H), 8.54 (s, 1H); MS (ESI) [M+1]+ 470.

Workup

  1. custompartitioned between methylene chloride (30 mL)
  2. extractionThe aqueous layer was extracted with methylene chloride (3×30 mL)
  3. washthe combined extracts were successively washed with water (30 mL), brine (30 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient)

Sources & evidence

ORD record
ord-b292c3c10b604e119fd7628bf70ae134
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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