Cesium carbonate → HCID 16039605, compound

HRID 1990163Notes

Reaction equation

HRID 1990163 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:21])[CH2:19][CH3:20])[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].[N:22]1([C:26]([C:28]2[CH:33]=[CH:32][C:31](Br)=[CH:30][N:29]=2)=[O:27])[CH2:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.C(OCC)(=O)C.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>[N:22]1([C:26]([C:28]2[N:29]=[CH:30][C:31]([O:1][C:2]3[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:21])[CH2:19][CH3:20])[CH:16]=3)[C:5]([NH:7][C:8]3[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=3)=[O:6])=[CH:32][CH:33]=2)=[O:27])[CH2:25][CH2:24][CH2:23]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineHCID 59127175HCID 59127175, compound

Product 1

HCID 16039605HCID 16039605, compound

Reagents, catalysts & solvents 3

HCID 11251615Bromotris(triphenylphosphine)copper(I)CatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 3-hydroxy-5-{[(1S)-1-methylpropyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.116 g, 0.4 mmol), 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (116 mg, 0.48 mmol), cesium carbonate (392 mg, 1.2 mmol) and bromotris(triphenylphosphine)copper(I) (38 mg, 0.04 mmol) in DMA (5 mL) was stirred in the microwave reactor at 160° C. for 4 hours. The product was dissolved in ethyl acetate (20 mL) and water (15 mL) and the layers separated. The organic layer was washed with brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a brown oil which was chromatographed on silica, eluting with a gradient of 0-5% methanol in ethyl acetate, and then re-columned on silica, eluting with a gradient of 0-5% methanol in DCM, to give the desired compound as a white foam which crystallised on standing. The material was triturated with 50% ethyl acetate in hexane to give the required product as a white solid (95 mg). 1H NMR δ (CDCl3): 0.90 (t, 3H), 1.23 (d, 3H), 1.51-1.72 (m, 2H), 2.28 (quin, 2H), 3.73 (s, 3H), 4.18 (t, 2H), 4.28 (q, 1H), 4.64 (t, 2H), 6.67 (t, 1H), 6.72 (d, 1H), 6.99 (s, 1H), 7.15 (s, 1H), 7.22 (d, 1H), 7.31 (d, 1H), 8.04 (d, 1H), 8.26 (s, 1H), 8.41 (s, 1H); m/z 450 (M+H)+

Workup

  1. customwater (15 mL) and the layers separated
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customto give a brown oil which
  7. customwas chromatographed on silica
  8. washeluting with a gradient of 0-5% methanol in ethyl acetate
  9. washre-columned on silica, eluting with a gradient of 0-5% methanol in DCM

Sources & evidence

ORD record
ord-394448b7a53d45fdaef3a86d5ff4efa8
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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