1-[(2-methyl-5,8-dihydro-4-quinolinyl)methyl]-1H-indole-5-carbonyl chloride → methyl {4-[({1-[(2-methyl-5,8-dihydro-4-quinolinyl)methyl]-1H-indol-5-yl}carbonyl)amino]tetrahydro-2H-pyran-4-yl}acetate

HRID 2299114Notes

Reaction equation

HRID 2299114 reaction equation
[NH2:1][C:2]1([CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[CH3:13][C:14]1[CH:23]=[C:22]([CH2:24][N:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34](Cl)=[O:35])=[CH:31][CH:32]=3)[CH:27]=[CH:26]2)[C:21]2[CH2:20][CH:19]=[CH:18][CH2:17][C:16]=2[N:15]=1>C(Cl)Cl.O>[CH3:13][C:14]1[CH:23]=[C:22]([CH2:24][N:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([NH:1][C:2]4([CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH2:3][CH2:4][O:5][CH2:6][CH2:7]4)=[O:35])=[CH:31][CH:32]=3)[CH:27]=[CH:26]2)[C:21]2[CH2:20][CH:19]=[CH:18][CH2:17][C:16]=2[N:15]=1

Participants

5

Reactant 2

HCID 222583801-[(2-methyl-5,8-dihydro-4-quinolinyl)methyl]-1H-indole-5-carbonyl chlorideHCID 25418820Methyl 4-aminotetrahydro-2H-pyran-4-acetate

Product 1

HCID 86584279methyl {4-[({1-[(2-methyl-5,8-dihydro-4-quinolinyl)methyl]-1H-indol-5-yl}carbonyl)amino]tetrahydro-2H-pyran-4-yl}acetateYield 17.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

The methyl (4-aminotetrahydro-2H-pyran-4-yl)acetate (0.13 g, 0.75 mmol) from example (355) was combined with the acid chloride (0.20 g, 0.49 mmol) from step (402b) in methylene chloride (15 ml) and water saturated sodium bicarbonate (15 ml). The reaction was stirred for 3.5 hs, partitioned between methylene chloride and water. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to give a solid. This was purified by flash chromatography on silica gel eluting hexane: ethyl acetate (25:75, v:v) to give the methyl {4-[({1-[(2-methyl-5,8-dihydro-4-quinolinyl)methyl]-1H-indol-5-yl}carbonyl)amino]tetrahydro-2H-pyran-4-yl}acetate (0.04 g, 17%) as a solid, MS (M+H)+=472.

Workup

  1. custompartitioned between methylene chloride and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customto give a solid
  6. customThis was purified by flash chromatography on silica gel
  7. washeluting hexane: ethyl acetate (25:75, v:v)

Sources & evidence

ORD record
ord-feddc33fd1e047bc882d8125de088ad3
Source dataset
uspto-grants-2002_12
Patent number
US06495565B2

Reaction notes

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