Dichloromethane → HCID 86711771, compound

HRID 528498Notes

Reaction equation

HRID 528498 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[O:6][CH2:7][CH2:8][N:9]([CH3:12])[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=2)O1.C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[CH3:12][N:9]1[CH2:8][CH2:7][O:6][C:5]2[C:4]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:3][C:2]([C:27]3[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=3)=[N:11][C:10]1=2

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 86711770HCID 86711770, compound

Product 1

HCID 86711771HCID 86711771, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-8-methyl-4-morpholin-4-yl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazine (120 mg, 0.44 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (196 mg, 0.88 mmol), PdCl2dppf.DCM (36 mg, 0.04 mmol) and cesium carbonate (573 mg, 1.76 mmol) in dioxane (5 mL) and water (0.5 mL) was degassed and heated at 100° C. for 18 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue 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 column chromatography (SiO2, gradient 0-5% methanol in DCM) then triturated with diethyl ether affording 119 (357 mg, 24%). LCMS: RT=3.04 min, [M+H]+=330. 1H NMR (400 MHz, DMSO): δ 8.94 (2H, s), 6.92 (2H, s), 4.16 (2H, t, J=4.37 Hz), 3.67 (4H, t, J=4.57 Hz), 3.52 (4H, t, J=4.56 Hz), 3.48 (2H, t, J=4.36 Hz), 3.13 (3H, s).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  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 column chromatography (SiO2, gradient 0-5% methanol in DCM)
  8. customthen triturated with diethyl ether affording 119 (357 mg, 24%)

Sources & evidence

ORD record
ord-0a493200a67b448597bee1cd73dc8d4c
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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