Sodium Chloride → 4-(1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)morpholine

HRID 1025624Notes

Reaction equation

HRID 1025624 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:9]=[CH:10][C:5]2=[CH:4][CH:3]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.CC(C)([O-])C.[Na+].[Na+].[Cl-]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH:12]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[N:8]1[C:6]2=[N:7][C:2]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[CH:3][CH:4]=[C:5]2[CH:10]=[CH:9]1)([CH3:14])[CH3:13]

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 8083MorpholineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 23676156Sodium t-butoxideHCID 580876901H-Pyrrolo[2,3-b]pyridine, 6-bromo-1-[tris(1-methylethyl)silyl]-

Product 1

HCID 710085494-(1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)morpholineYield 86.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

In a 25 mL round-bottomed flask, 6-bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (800 mg, 2.26 mmol, Eq: 1.00), palladium (II) acetate (254 mg, 1.13 mmol, Eq: 0.5) and tri-tert-butylphosphine (229 mg, 279 μl, 1.13 mmol, Eq: 0.5) were combined with toluene to give a yellow solution. Morpholine (789 mg, 789 μl, 9.06 mmol, Eq: 4) and sodium tert-butoxide (653 mg, 6.79 mmol, Eq: 3) were added. The reaction mixture was heated to 80° C. and stirred for 1 h. The reaction mixture was poured into 20 mL sat NaCl and extracted with EtOAc (3×20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 10% to 15% EtOAc in hexanes) to give 4-(1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)morpholine (703 mg, 86%) as a light brown oil.

Workup

  1. customto give a yellow solution
  2. additionThe reaction mixture was poured into 20 mL
  3. extractionextracted with EtOAc (3×20 mL)
  4. dry with materialThe organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 80 g, 10% to 15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b59c017c85a04f2cb940cb6793593f7e
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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