Morpholine → HCID 11773517, compound

HRID 1984979Notes

Reaction equation

HRID 1984979 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[C:19](Br)[CH:20]=4)[CH:15]=3)=[O:13])[CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.[NH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[C:19]([N:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)[CH:20]=4)[CH:15]=3)=[O:13])[CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 11337876HCID 11337876, compound

Product 1

HCID 11773517HCID 11773517, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6-bromo-naphthalene-2-carboxylic acid quinolin-7-ylamide, Example 32(b), (40 mg, 0.106 mmol) in dioxane (2 mL) was added tris(dibenzylideneacetone)dipalladium(0) (5 mg, Aldrich), biphenyl-2-yl-di-tert-butyl-phosphane (5 mg, Strem), morpholine (74 mg, 0.85 mmol, Aldrich) and lithium bis(trimethylsilyl)amide (0.53 ml of 1 M solution in THF, 0.53 mmol, Aldrich). The mixture was heated in microwave at 150° C. for 5 min, cooled to room temperature, and partitioned between satd NH4Cl (5 mL) and EtOAc (30 mL). The EtOAc layer was separated, washed with brine, dried over MgSO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography (gradient, 5 to 10% (2 M NH3 in MeOH) in CH2Cl2) to provide the title compound as a yellow amorphous solid. MS (ESI, pos. ion) m/z: 384 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between satd NH4Cl (5 mL) and EtOAc (30 mL)
  3. customThe EtOAc layer was separated
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customThe filtrate was evaporated in vacuo
  8. customthe residue was purified by silica gel column chromatography (gradient, 5 to 10% (2 M NH3 in MeOH) in CH2Cl2)

Sources & evidence

ORD record
ord-21cbad227d4546db98d0a91743ef1b6c
Source dataset
uspto-grants-2009_06
Patent number
US07544803B2

Reaction notes

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