Sodium Carbonate → N-[3-(7,7-dimethyl-4-morpholino-6H-[1,4]dioxino[2,3-d]pyrimidin-2-yl)phenyl]methanesulfonamide

HRID 528486Notes

Reaction equation

HRID 528486 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][S:21]([NH:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)(=[O:23])=[O:22].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>[CH3:12][C:9]1([CH3:13])[O:8][C:6]2[N:7]=[C:2]([C:29]3[CH:30]=[C:25]([NH:24][S:21]([CH3:20])(=[O:22])=[O:23])[CH:26]=[CH:27][CH:28]=3)[N:3]=[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:5]=2[O:11][CH2:10]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27735353-Methylsulfonylaminophenylboronic acidHCID 867117472-Chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Product 1

HCID 73427141N-[3-(7,7-dimethyl-4-morpholino-6H-[1,4]dioxino[2,3-d]pyrimidin-2-yl)phenyl]methanesulfonamideYield 15%

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), 3-(methanesulfonylamino)phenylboronic acid (57 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. for 30 minutes 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 reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient of acetonitrile 5-98%) affording 114 as a white solid (11 mg, 15%). LCMS: RT=4.22 min, [M+H]+=421. 1H NMR (400 MHz, CDCl3): δ 8.19-8.12 (1H, m), 8.05-8.02 (1H, m), 7.44-7.37 (2H, m), 6.34 (1H, broad s), 3.92 (2H, s), 3.88-3.79 (8H, m), 3.00 (3H, 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 reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient of acetonitrile 5-98%)

Sources & evidence

ORD record
ord-3250f35d5bcc4c3cb65d3ea92f6b73ca
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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