Morpholine → HCID 44539731, compound

HRID 1616033Notes

Reaction equation

HRID 1616033 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:19]=[C:18]([C:20]3[CH:28]=[CH:27][CH:26]=[C:25]4[C:21]=3[CH:22]=[CH:23][NH:24]4)[CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][NH:15]3)=[O:9])=[N:6][CH:7]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].CS(C)=O.CO>[NH:24]1[C:25]2[C:21](=[C:20]([C:18]3[CH:17]=[C:16]4[C:12]([CH:13]=[N:14][NH:15]4)=[C:11]([NH:10][C:8]([C:5]4[CH:4]=[CH:3][C:2]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)=[CH:7][N:6]=4)=[O:9])[CH:19]=3)[CH:28]=[CH:27][CH:26]=2)[CH:22]=[CH:23]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 44540317HCID 44540317, compound

Product 1

HCID 44539731HCID 44539731, compoundYield 22.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 22036561Dimethyl sulfoxide methanolSolvent

Conditions

Temperature
150 °C

Procedure

5-Bromo-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide (35 mg, 0.08 mmol) and morpholine (1 ml, 11.5 mmol) were placed in a microwave vial. Pd2dba3 (4 mg, 0.004 mmol), BINAP (5 mg, 0.008 mmol) and cesium carbonate (40 mg, 0.12 mmol) were added and the mixture was heated at 150° C. for 75 mins under microwave irradiation. The reaction mixture was concentrated in vacuo to give a crude residue that was suspended in 1:1 DMSO/MeOH (1 ml) and filtered to give an orange solution that was purified by Mass Directed Automated Preparative HPLC (Method C). The product was loaded onto a 1 g aminopropyl column, eluted with MeOH and the solvent removed under a stream of nitrogen to give the title compound (8 mg) as a pale orange solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto give a crude residue that
  3. filtrationfiltered
  4. customto give an orange solution that
  5. customwas purified by Mass Directed Automated Preparative HPLC (Method C)
  6. washeluted with MeOH
  7. customthe solvent removed under a stream of nitrogen

Sources & evidence

ORD record
ord-a135e9b44c7749daa90fd7a9e61f4d87
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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