Potassium Phosphate, Tribasic → 5-Phenyl4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine

HRID 2246375Notes

Reaction equation

HRID 2246375 reaction equation
C1(S([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([N:19]4[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]4)[C:13]=3[C:12](Br)=[CH:11]2)(=O)=O)C=CC=CC=1.[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:26]1([C:12]2[C:13]3[C:18]([N:19]4[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]4)=[N:17][CH:16]=[N:15][C:14]=3[NH:10][CH:11]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 224845025-Bromo-7-(phenylsulfonyl)-4-(piperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 224845445-Phenyl4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidineYield 20%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of the product from Method V (100 mg/0.237 mmol) in 1.0 mL of dioxane was added 32 mg (0.261 mmol) of phenylboronic acid and 75 mg (0.356 mmol) of tribasic potassium phosphate followed by 7 mg (0.006 mmol) of tetrakis(triphenylphosphine) palladium. The resulting mixture was degassed with nitrogen and stirred at 100° C. for 48 h. After cooling to room temperature, 1.0 mL of methanol was added followed by 50 mg of NaOH and the new mixture stirred at room temperature for 1 h. The resulting mixture was then partitioned between dichloromethane and water, the dichloromethane layer dried over MgSO4 and concentrated to dryness in vacuo. The crude product was purified by silica-gel chromatography (2:1 ethyl acetate/hexanes) affording 13 mg (20%) of the title compound. 1H NMR (400 MHz) (CDCl3) δ: 1.33-1.34 (m, 4H), 1.43-1.44 (m, 2H), 3.26-3.28 (m, 4H), 7.12 (s, 1H), 7.27 (t, 1H, J=7.2 Hz), 7.38 (t, 2H, J=8.0 Hz), 7.45 (d, 2H, J=0.8 Hz), 8.42 (s, 1H). LRMS: 279.2 (M+1).

Workup

  1. customThe resulting mixture was degassed with nitrogen
  2. temperatureAfter cooling to room temperature
  3. addition1.0 mL of methanol was added
  4. stirringthe new mixture stirred at room temperature for 1 h
  5. customThe resulting mixture was then partitioned between dichloromethane and water
  6. dry with materialthe dichloromethane layer dried over MgSO4
  7. concentrationconcentrated to dryness in vacuo
  8. customThe crude product was purified by silica-gel chromatography (2:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ba7916eac636422a9e7ab5693bcc2ff0
Source dataset
uspto-grants-2010_03
Patent number
US07687507B2

Reaction notes

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