Potassium Phosphate, Tribasic → HCID 86703940, compound

HRID 1049943Notes

Reaction equation

HRID 1049943 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[CH:14][N:13]=[C:12]3[NH2:19])O1.Br[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][CH2:29][CH2:30][N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[CH:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O1CCOCC1>[N:31]1([CH2:30][CH2:29][NH:28][C:24]2[CH:23]=[C:22]([C:9]3[CH:10]=[C:11]4[C:16](=[CH:17][CH:18]=3)[N:15]=[CH:14][N:13]=[C:12]4[NH2:19])[CH:27]=[CH:26][N:25]=2)[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 67086224HCID 67086224, compoundHCID 86703939HCID 86703939, compound

Product 1

HCID 86703940HCID 86703940, compound

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To an 8 mL screw-cap vial was added 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-4-amine (26 mg; 0.096 mmol, 26 mg) followed by 4-bromo-N-(2-pyrrolidin-1-ylethyl)pyridin-2-amine (2 equiv., 0.19 mmol, 52 mg, Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.05 equiv., 0.005 mmol, 4 mg, dioxane (0.4 mL), and potassium phosphate tribasic (2M in water, 4 equiv., 0.38 mmol, 0.19 mL). The reaction was capped and shaken for 1 h at 100° C. The reaction was then cooled to room temperature, then extracted. The aqueous was further extracted with dichloromethane, and combined with the dioxane extract and concentrated. The crude was purified by reverse phase HPLC, yielding 5 mg of desired product. 1H NMR (400 MHz, DMSO) δ 8.62-8.56 (s, 1H), 8.42-8.38 (s, 1H), 8.32-8.16 (m, 2H), 8.11-8.02 (m, 2H), 7.77-7.72 (d, J=8.7 Hz, 1H), 6.98-6.92 (d, J=5.4 Hz, 1H), 6.90-6.84 (s, 1H), 6.53-6.44 (t, J=5.4 Hz, 1H), 3.49-3.40 (t, J=6.7 Hz, 2H), 2.73-2.65 (t, J=6.7 Hz, 2H), 2.64-2.55 (m, 4H), 1.80-1.63 (m, 4H). LCMS M/Z (M+H)=335.

Workup

  1. customTo an 8 mL screw-cap vial
  2. customThe reaction was capped
  3. temperatureThe reaction was then cooled to room temperature
  4. extractionextracted
  5. extractionThe aqueous was further extracted with dichloromethane
  6. extractionextract
  7. concentrationconcentrated
  8. customThe crude was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-05ad7b8c7ab44920a82bf31355b2c546
Source dataset
uspto-grants-2016_07
Patent number
US09382241B2

Reaction notes

Loading…