Morpholine → HCID 23003158, compound

HRID 396197Notes

Reaction equation

HRID 396197 reaction equation
[C:1]([CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][C:17]3[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:24])=[CH:12][CH:13]=2)[CH:8]=[C:7]1[C:25](O)=[O:26])#[N:2].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1.C(N(C(C)C)CC)(C)C>CN(C)C=O.ClCCl>[Cl:23][C:22]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:24])[C:17]=1[CH2:16][O:15][C:11]1[CH:10]=[C:9]2[C:14](=[CH:13][CH:12]=1)[N:6]([CH2:5][CH2:4][CH2:3][C:1]#[N:2])[C:7]([C:25]([N:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1)=[O:26])=[CH:8]2

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 23003155HCID 23003155, compound

Product 1

HCID 23003158HCID 23003158, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-(3-Cyanopropyl)-5-(2,6-dichlorobenzyloxy)-1H-indole-2-carboxylic acid (0.10 g, 0.25 mmol) was dissolved in dimethylformamide (15 mL). PyBroP (bromo-tris-pyrrolidino-phosphonium hexafluorophosphate) (0.13 g, 0.27 mmol) was added followed by morpholine (0.065 g, 0.74 mmol), diisopropylethylamine (0.13 g, 0.99 mmol), and a catalytic amount of N,N-dimethylaminopyridine. The reaction mixture was stirred for 18 h under argon at ambient temperature. The solution was diluted with dichloromethane and washed with water (3×) and brine. The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure. Purification by flash chromatography (silica gel, 25% acetone/chloroform) yielded an off-white solid (0.11 g, 95%). MS(ES) m/e 472.2 [M +H]+.

Workup

  1. washwashed with water (3×) and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure
  5. customPurification by flash chromatography (silica gel, 25% acetone/chloroform)

Sources & evidence

ORD record
ord-6c71dea4260747f8a4f461dea0adb98a
Source dataset
uspto-grants-2003_08
Patent number
US06608059B1

Reaction notes

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