Morpholine → HCID 52913523, compound

HRID 577263Notes

Reaction equation

HRID 577263 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[CH2:5][N:6]1[C:10]2=[N:11][C:12]([NH:15][C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)=[N:13][CH:14]=[C:9]2[CH:8]=[N:7]1.C([O-])([O-])=O.[Cs+].[Cs+].[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH3:21][N:19]1[CH:20]=[C:16]([NH:15][C:12]2[N:11]=[C:10]3[N:6]([CH2:5][C:4]4[CH:22]=[CH:23][CH:24]=[C:2]([N:31]5[CH2:36][CH2:35][O:34][CH2:33][CH2:32]5)[CH:3]=4)[N:7]=[CH:8][C:9]3=[CH:14][N:13]=2)[CH:17]=[N:18]1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 66765269HCID 66765269, compound

Product 1

HCID 52913523HCID 52913523, compoundYield 52.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

1-(3-iodobenzyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (80 mg, 0.185 mmol), was dissolved in dioxane (1.2 mL) and added to a microwave tube. A mixture of Cs2CO3 (150 mg, 0.462 mmol) and X-Phos ligand (dicyclohexyl(2′,4′,6′-triisopropyl-[1,1-biphenyl]-2-yl)phosphine, 4.4 mg, 9.2 μmol) and morpholine (40 μL, 0.462 mmol) was then added to the stirred solution, followed by the catalyst Pd2(dba)3 (1.65 mg, 1.8 μmol). The solution was degassed for 5 minutes with nitrogen and the tube was sealed under Nitrogen. The tube was heated in the microwave oven for 1 h at 140° C. then the mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with ethyl acetate and the combined organics were washed with brine and dried over Na2SO4. The solution was then filtered and the solvent removed in vacuo to obtain a crude solid which was purified by flash chromatography (ethyl acetate 100% to ethyl acetate/MeOH=85:15) to give the title compound as a white solid (38 mg, 52% yield). 1H NMR (d6-DMSO) δ 9.83 (br s, 1H), 8.91 (s, 1H), 8.08-7.98 (m, 2H), 7.59 (s, 1H), 7.15 (t, 1H), 7.03 (s, 1H), 6.84 (dd, J=8.2, 2.1 Hz, 1H), 6.69 (d, J=6.1 Hz, 1H), 5.49 (s, 2H), 3.84 (s, 3H), 3.72-3.63 (m, 4H), 3.07-2.95 (m, 4H); LC-MS method B, (ES+) 391.0, RT=7.44 min.

Workup

  1. additionadded to a microwave tube
  2. additionwas then added to the stirred solution
  3. customThe solution was degassed for 5 minutes with nitrogen
  4. customthe tube was sealed under Nitrogen
  5. additionthe mixture was diluted with ethyl acetate
  6. washwashed with water
  7. extractionThe aqueous phase was extracted with ethyl acetate
  8. washthe combined organics were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationThe solution was then filtered
  11. customthe solvent removed in vacuo
  12. customto obtain a crude solid which
  13. customwas purified by flash chromatography (ethyl acetate 100% to ethyl acetate/MeOH=85:15)

Sources & evidence

ORD record
ord-0542267444c3485c91d2d56b8a78bddc
Source dataset
uspto-grants-2015_05
Patent number
US09040545B2

Reaction notes

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