Morpholine → HCID 67142093, compound

HRID 1445105Notes

Reaction equation

HRID 1445105 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[CH:9]=[C:10]2[C:26]([CH3:27])=[C:25]([CH3:28])[N:24]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)[C:11]2=[C:12]([N:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)[N:13]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[ClH:7].[F:36][C:32]1[CH:31]=[C:30]([CH:35]=[CH:34][CH:33]=1)[CH2:29][N:24]1[C:11]2=[C:12]([N:14]3[CH2:23][CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH2:15]3)[N:13]=[C:8]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[CH:9]=[C:10]2[C:26]([CH3:27])=[C:25]1[CH3:28]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86615262HCID 86615262, compound

Product 1

HCID 67142093HCID 67142093, compoundYield 32%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

Morpholine (96.7 μl, 1.11 mmol) was added to a solution of 2-[5-chloro-1-(3-fluorobenzyl)-2,3-dimethyl-1H-pyrrolo[2,3-c]pyridin-7-yl-]1,2,3,4-tetrahydroisoquinoline (300 mg, 0.714 mmol) prepared in Example 662, tris(dibenzylideneacetone)dipalladium(0) (16.3 mg, 0.018 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-xanthene (31 mg, 0.054 mmol), and cesium carbonate (326 mg, 1.0 mmol) in anhydrous 1,4-dioxane (5 ml). The reaction mixture was refluxed for 40 hours at 80° C. and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/5, v/v). The resulting product was dissolved in ethyl acetate, saturated with hydrochloric acid gas, and then filtered to give 115 mg of the titled compound as a white solid (Yield: 32%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/5
  3. dissolutionThe resulting product was dissolved in ethyl acetate, saturated with hydrochloric acid gas
  4. filtrationfiltered

Sources & evidence

ORD record
ord-0c5d95c6a04f4f23828034f3f2cb5521
Source dataset
uspto-grants-2010_02
Patent number
US07662832B2

Reaction notes

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