Sodium Carbonate → 2-(2-methoxypyrimidin-5-yl)-7,7-dimethyl-4-morpholino-6H-[1,4]dioxino[2,3-d]pyrimidine

HRID 528482Notes

Reaction equation

HRID 528482 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[O:11][CH2:10][C:9]([CH3:13])([CH3:12])[O:8][C:6]=2[N:7]=1.[CH3:20][O:21][C:22]1[N:27]=[CH:26][C:25](B(O)O)=[CH:24][N:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:20][O:21][C:22]1[N:27]=[CH:26][C:25]([C:2]2[N:3]=[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:5]3[O:11][CH2:10][C:9]([CH3:13])([CH3:12])[O:8][C:6]=3[N:7]=2)=[CH:24][N:23]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 867117472-Chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Product 1

HCID 734271392-(2-methoxypyrimidin-5-yl)-7,7-dimethyl-4-morpholino-6H-[1,4]dioxino[2,3-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 2-chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine from Example 104 (50 mg, 0.18 mmol), 2-methoxypyrimidin-5-ylboronic acid (42 mg, 0.27 mmol), Pd(PPh3)2Cl2 (12 mg, 0.02 mmol) and sodium carbonate (0.5 mL, 0.5 mmol, 1M aqueous solution) in acetonitrile (1.5 mL) then evacuated and back filled with nitrogen before being heated at 120° C. using microwave irradiation. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with methanol and the product eluted with 2M ammonia in methanol. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by trituration with diethyl ether affording 110 as a white solid (30 mg, 17%). LCMS: RT=4.18 min, [M+H]+=360. 1H NMR (400 MHz, CDCl3): δ 9.33 (2H, s), 4.07 (3H, s), 3.92 (2H, s), 3.83 (8H, s), 1.47 (6H, s)

Workup

  1. customthen evacuated
  2. additionback filled with nitrogen
  3. custommicrowave irradiation
  4. washwas washed with methanol
  5. washthe product eluted with 2M ammonia in methanol
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by trituration with diethyl ether affording 110 as a white solid (30 mg, 17%)

Sources & evidence

ORD record
ord-105285ed5e414befaa6869c833f602b5
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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