Morpholine → 5-Morpholin-4-yl-1-(2-trimethylsilanylethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 2114067Notes

Reaction equation

HRID 2114067 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.[Cl-].[Na+].O.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:19]1([C:2]2[CH:3]=[C:4]3[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]3=[N:6][CH:7]=2)[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 598250161H-Pyrrolo[2,3-B]pyridine, 5-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-HCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 578301315-Morpholin-4-yl-1-(2-trimethylsilanylethoxymethyl)-1H-pyrrolo[2,3-b]pyridineYield 54%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 51 (1.48 g, 4.52 mmol), morpholine (0.473 mL, 5.43 mmol), Pd2(dba)3 (0.083 g, 0.090 mmol), Xantphos (0.157 g, 0.271 mmol) and t-BuONa (0.652 g, 6.78 mmol) in toluene (15 mL) was heated at 100° C. for 2.5 hours. The mixture was cooled and poured into brine and extracted with AcOEt. The organic layer was washed with brine, dried (MgSO4), and concentrated. The residue was purified by means of SGC with hexane: AcOEt as eluent to afford 52 (0.81 g, 54%) as a tan syrup. 1H NMR (400 MHz, CDCl3) δ 0.00 (s, 9H), 0.94-1.00 (m, 2H), 3.18-3.23 (m, 4H), 3.57-3.63 (m, 2H), 3.96-4.02 (m, 4H), 5.70 (s, 2H), 6.50 (d, J=0.35 Hz, 1H), 7.38 (d, J=0.35 Hz, 1H), 7.55 (d, J=0.26 Hz, 1H), 8.24 (d, J=0.26 Hz, 1H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with AcOEt
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by means of SGC with hexane

Sources & evidence

ORD record
ord-2ecd94b8abd44acb8267093ba95e0f3f
Source dataset
uspto-grants-2008_10
Patent number
US07432375B2

Reaction notes

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