4-Methylmorpholine → HCID 86603139, compound

HRID 855459Notes

Reaction equation

HRID 855459 reaction equation
C(O[C:4]([C:6]1[CH:7]=[C:8]([CH3:16])[C:9]([F:15])=[C:10]2[C:14]=1[NH:13][CH:12]=[CH:11]2)=[O:5])C.[OH-].[K+].[C:19]([C:23]1[CH:39]=[CH:38][C:26]([CH2:27][NH:28][CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)=[CH:25][CH:24]=1)([CH3:22])([CH3:21])[CH3:20].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[C:19]([C:23]1[CH:39]=[CH:38][C:26]([CH2:27][N:28]([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[C:4]([C:6]2[CH:7]=[C:8]([CH3:16])[C:9]([F:15])=[C:10]3[C:14]=2[NH:13][CH:12]=[CH:11]3)=[O:5])=[CH:25][CH:24]=1)([CH3:22])([CH3:20])[CH3:21]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 14797Potassium HydroxideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 29280418(4-Tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amineHCID 69346960HCID 69346960, compound

Product 1

HCID 86603139HCID 86603139, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-fluoro-5-methyl-1H-indole-7-carboxylic acid ethyl ester (50 mg, 0.23 mmol) in THF (0.7 mL) was treated with 2 M aq. potassium hydroxide solution (0.23 mL, 0.46 mmol), and the reaction mixture was heated under reflux. After 64 h, the solution was evaporated, the residue dissolved in DMF (3.2 mL) and treated with (4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine (71 mg, 0.25 mmol), N-methylmorpholine (69 mg, 0.68 mmol), and HBTU (129 mg, 0.34 mmol). After 16 h, the reaction mixture was partitioned between water and EtOAc, the organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography of the residue (SiO2, heptane-EtOAc gradient) afforded the title compound (71 mg, 68%). Yellow oil, MS (EI) 176.1 (100), 351.2 (19), 460.2 (14, M+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux
  3. customthe solution was evaporated
  4. dissolutionthe residue dissolved in DMF (3.2 mL)
  5. waitAfter 16 h
  6. customthe reaction mixture was partitioned between water and EtOAc
  7. washthe organic layer was washed with brine
  8. dry with materialdried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-b5434bb0c43b42dd8d72b4755a4d6b11
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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