1,4-Dioxane → HCID 86710199, compound

HRID 2284435Notes

Reaction equation

HRID 2284435 reaction equation
[C:1]([O:4][CH2:5][O:6][C:7](=[O:35])[N:8]([C:32](=[O:34])[CH3:33])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[CH:24]=[N:23][C:22]3[C:21]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[N:20][C:19](Cl)=[N:18][C:17]=3[CH:16]=2)[CH:10]=1)(=[O:3])[CH3:2].CC1(C)C(C)(C)OB([C:44]2[CH:45]=[N:46][C:47]([NH2:50])=[N:48][CH:49]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C(Cl)(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:1]([O:4][CH2:5][O:6][C:7](=[O:35])[N:8]([C:32](=[O:34])[CH3:33])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[CH:24]=[N:23][C:22]3[C:21]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[N:20][C:19]([C:44]4[CH:45]=[N:46][C:47]([NH2:50])=[N:48][CH:49]=4)=[N:18][C:17]=3[CH:16]=2)[CH:10]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 86710198HCID 86710198, compound

Product 1

HCID 86710199HCID 86710199, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
82 °C

Procedure

To a 50 mL sealed tube, ((acetyl(3-(2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)carbamoyl)oxy)methyl acetate (0.96 g, 0.0019 mol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (0.852 g, 0.0038 mol), potassium phosphate tribasic (0.81 g, 0.0038 mol), 1,4-dioxane (45 mL), and water (4 mL) were added. The reaction mixture was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)4 (0.11 g, 0.000096 mol) was added and the mixture was degassed with N2 for 5-10 min. The reaction mixture was stirred at 82° C. for 30 minutes. The volatiles were evaporated to provide a residue. The residue was dissolved in chloroform. The chloroform layer was washed with water, brine, dried over anhydrous sodium sulphate and evaporated under reduced pressure to provide a crude solid. The crude solid was purified by flash column chromatography (0-2% methanol in chloroform) to provide a solid. The solid was washed with methanol to provide the title compound as a light yellow solid (0.4 g, 40%). 1H NMR (400 MHz, DMSO-d6): δ 9.18 (s, 2H), 9.08 (s, 1H), 8.35 (s, 1H), 7.98 (d, J=8.0 Hz, 1H), 7.91 (br s, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.35 (d, J=7.6 Hz, 1H), 7.20 (br s, 2H), 5.68 (s, 2H), 4.52 (br s, 4H), 3.84 (t, J=4.0 Hz, 4H), 2.57 (s, 3H), 2.06 (s, 3H). LC-MS (ESI): Calculated mass: 558.20; Observed mass [M+H]+: 558.8 (RT: 0.40 min).

Workup

  1. customTo a 50 mL sealed tube
  2. customThe reaction mixture was degassed with N2 for 5-10 minutes
  3. customthe mixture was degassed with N2 for 5-10 min
  4. customThe volatiles were evaporated
  5. customto provide a residue
  6. washThe chloroform layer was washed with water, brine
  7. dry with materialdried over anhydrous sodium sulphate
  8. customevaporated under reduced pressure
  9. customto provide a crude solid
  10. customThe crude solid was purified by flash column chromatography (0-2% methanol in chloroform)
  11. customto provide a solid
  12. washThe solid was washed with methanol

Sources & evidence

ORD record
ord-b831349eca1c4be1b10f891ca0e9f01c
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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