Potassium Carbonate → HCID 67055979, compound

HRID 2036824Notes

Reaction equation

HRID 2036824 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([CH:40]([CH3:43])[C:41]#[N:42])[CH:37]=[N:38][CH:39]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[C:20]1([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:11][C:2]([C:34]2[CH:35]=[C:36]([CH:40]([CH3:43])[C:41]#[N:42])[CH:37]=[N:38][CH:39]=2)=[N:3]3)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 67055991HCID 67055991, compoundHCID 866706132-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

Product 1

HCID 67055979HCID 67055979, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (from example 1, step 4, 0.12 g, 0.5 mmol) in 1,4-dioxane (8 mL) and H2O (0.55 mL) under nitrogen was added 2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)propanenitrile (0.120 g, 0.4 mmol) and potassium carbonate (0.14 g, 1 mmol). The resulting mixture was degassed with nitrogen for 15 min. After this time, (1,1′-bis(diphenylphosphino)ferrocene)palladium (II) chloride dichloromethane complex (0.26 mg, 0.036 mmol) was added and the reaction mixture was again degassed with nitrogen for 10 min. At the conclusion of this period, the reaction mixture was stirred at 95° C. for 16 h. The reaction mixture was then allowed to cool to room temperature. Once at the prescribed temperature, the reaction mixture was quenched by the addition of water and then transferred to a separation funnel. The aqueous layer was extracted with ethyl acetate. The combined organic portions were washed with water and saturated NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting concentrate was purified by silica gel column chromatography using 1% methanol in DCM to afford racemic 2-(5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridin-3-yl)propanenitrile (95 mg, 63% yield) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.60 (s, 1H), 8.80 (d, 1H, J=2 Hz); 8.77 (s, 1H); 8.26 (d, 1H, J=6 Hz); 7.92 (dd, 1H, J=1.2, 6.8 Hz); 7.85 (t, 1H, J=6.8 Hz); 7.73 (dt, 1H, J=1.6, 7.6 Hz); 7.58-7.52 (m, 5H); 7.34-7.32 (m, 2H); 7.24 (t, 1H, 7.2 Hz); 6.86 (t, 1H, J=4 Hz); 4.76 (d, 2H, J=4.4 Hz); 4.59 (q, 1H, J=7.2 Hz); 1.68 (d, 3H, 7.2 Hz). LCMS Method Y: retention time 1.68 min, [M+1]=443.2.

Workup

  1. customThe resulting mixture was degassed with nitrogen for 15 min
  2. additionAfter this time, (1,1′-bis(diphenylphosphino)ferrocene)palladium (II) chloride dichloromethane complex (0.26 mg, 0.036 mmol) was added
  3. customthe reaction mixture was again degassed with nitrogen for 10 min
  4. temperatureto cool to room temperature
  5. customOnce at the prescribed temperature, the reaction mixture was quenched by the addition of water
  6. customtransferred to a separation funnel
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. washThe combined organic portions were washed with water and saturated NaCl
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. concentrationThe resulting concentrate
  13. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-68d0016f826d4b3c9fcd3e7180596a72
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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