Cesium carbonate → HCID 53629555, compound

HRID 1011799Notes

Reaction equation

HRID 1011799 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].[N:24]1([C:28]([C:30]2[CH:35]=[CH:34][C:33](Br)=[CH:32][N:31]=2)=[O:29])[CH2:27][CH2:26][CH2:25]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[N:24]1([C:28]([C:30]2[N:31]=[CH:32][C:33]([O:1][C:2]3[CH:3]=[C:4]([CH:14]=[C:15]([O:17][CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[CH:16]=3)[C:5]([NH:7][C:8]3[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=3)=[O:6])=[CH:34][CH:35]=2)=[O:29])[CH2:27][CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineHCID 59127166HCID 59127166, compound

Product 1

HCID 53629555HCID 53629555, compoundYield 21.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
200 °C

Procedure

3-Hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-(tetrahydro-2H-pyran-4-yloxy)benzamide (200 mg, 0.63 mmol), 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (184 mg, 0.76 mmol), bromotris(triphenylphosphine)copper (186 mg, 0.2 mmol) and caesium carbonate (411 mg, 1.26 mmol) were dissolved/suspended in DMA (3.5 mL). The reaction mixture was heated in a microwave reactor for 1 hour at 200° C. then allowed to cool, filtered and reduced in vacuo. Water (25 mL) was added and the product extracted with ethyl acetate (2×25 mL), the organics dried (MgSO4) then purified by chromatography on silica, eluting with 0-10% methanol in DCM, to give the desired compound as a pale yellow foam (65 mg). 1H NMR 8 (d6-DMSO): 1.57-1.67 (m, 2H), 1.97-2.05 (m, 2H), 2.23-2.34 (m, 2H), 3.51 (t, 2H), 3.78 (s, 3H), 3.83-3.90 (m, 2H), 4.08 (t, 2H), 4.59 (t, 2H), 4.69-4.76 (m, 1H), 6.56 (d, 1H), 7.00 (t, 1H), 7.29 (t, 1H), 7.49 (t, 1H), 7.54-7.58 (m, 1H), 7.60 (d, 1H), 8.00 (d, 1H), 8.41 (d, 1H), 10.83 (s, 1H); m/z 478 (M+H)+

Workup

  1. temperatureto cool
  2. filtrationfiltered
  3. additionWater (25 mL) was added
  4. extractionthe product extracted with ethyl acetate (2×25 mL)
  5. dry with materialthe organics dried (MgSO4)
  6. customthen purified by chromatography on silica
  7. washeluting with 0-10% methanol in DCM

Sources & evidence

ORD record
ord-6630072e6e2d4c4cb044990fc49d98bd
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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