Sodium Carbonate → 2-[2-(4-aminophenyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol

HRID 1095416Notes

Reaction equation

HRID 1095416 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C(Cl)Cl.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>[NH2:31][C:30]1[CH:32]=[CH:33][C:27]([C:2]2[N:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]3[CH3:18])[N:3]=2)=[CH:28][CH:29]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 593801562-[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol

Product 1

HCID 595083982-[2-(4-aminophenyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-olYield 60.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Dichlorobis(triphenylphosphine)palladium(II) (0.492 g, 0.70 mmol) was added to 2-[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol (3.81 g, 14.02 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.38 g, 15.42 mmol) and sodium carbonate (4.46 g, 42.06 mmol) in DME (80 mL) and water (20.00 mL) under nitrogen. The resulting solution was stirred at 80° C. for 6 hours. The reaction mixture was diluted with DCM (200 mL), and washed with water (400 mL) twice. The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20 to 60% ethyl acetate in isohexane, to give a material which was further purified by ion exchange chromatography using an SCX column, eluting with 2M ammonia in methanol, to give the desired material as a pink gum (2.78 g).

Workup

  1. washwashed with water (400 mL) twice
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 20 to 60% ethyl acetate in isohexane
  7. customto give a material which
  8. customwas further purified by ion exchange chromatography
  9. washeluting with 2M ammonia in methanol

Sources & evidence

ORD record
ord-e54eb3618dd848f2a7878edab3be4807
Source dataset
uspto-grants-2012_03
Patent number
US08138183B2

Reaction notes

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