Ethyl Acetate → 3-{[2-(azetidin-1-ylcarbonyl)pyrimidin-5-yl]oxy}-5-[(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1011714Notes

Reaction equation

HRID 1011714 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][CH:18]([CH3:20])[CH3:19])[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].[N:21]1([C:25]([C:27]2[N:32]=[CH:31][C:30](Br)=[CH:29][N:28]=2)=[O:26])[CH2:24][CH2:23][CH2:22]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CC(N(C)C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]Br.O>[N:21]1([C:25]([C:27]2[N:28]=[CH:29][C:30]([O:1][C:2]3[CH:3]=[C:4]([CH:14]=[C:15]([O:17][CH:18]([CH3:20])[CH3:19])[CH:16]=3)[C:5]([NH:7][C:8]3[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=3)=[O:6])=[CH:31][N:32]=2)=[O:26])[CH2:24][CH2:23][CH2:22]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 536296392-(Azetidin-1-ylcarbonyl)-5-bromopyrimidineHCID 591271833-hydroxy-5-isopropoxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 536295393-{[2-(azetidin-1-ylcarbonyl)pyrimidin-5-yl]oxy}-5-[(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 50.1%

Reagents, catalysts & solvents 3

HCID 11251615Bromotris(triphenylphosphine)copper(I)CatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 3-hydroxy-5-[(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (250 mg, 0.91 mmol), 2-(azetidin-1-ylcarbonyl)-5-bromopyrimidine (242 mg, 1.0 mmol), cesium carbonate (886 mg, 2.72 mmol) and bromotris(triphenylphosphine)copper(I) (423 mg, 0.45 mmol) in DMA (5 mL) was stirred in a ‘Biotage initiator Microwave’ at 160° C. for 4 hours. The mixture was added to ethyl acetate (50 mL) and water (50 mL), the organic layer washed with brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a brown oil. The residue was chromatographed on silica, eluting with a gradient of 0-10% methanol in ethyl acetate, to give the desired compound (199 mg).

Workup

  1. washthe organic layer washed with brine (50 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent removed in vacuo
  5. customto give a brown oil
  6. customThe residue was chromatographed on silica
  7. washeluting with a gradient of 0-10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-281b6afa924141fab22dde8d030bbdad
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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