Cesium carbonate → 3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-ylmethyl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 1505709Notes

Reaction equation

HRID 1505709 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12]OS(C)(=O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:24][N:25]1[CH:29]=[C:28]([C:30]2[CH:31]=[C:32]([C:36]3[N:41]=[CH:40][C:39]([C:42]4[CH:43]=[N:44][NH:45][CH:46]=4)=[CH:38][N:37]=3)[CH:33]=[CH:34][CH:35]=2)[CH:27]=[N:26]1>CC(N(C)C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][N:44]2[CH:43]=[C:42]([C:39]3[CH:38]=[N:37][C:36]([C:32]4[CH:33]=[CH:34][CH:35]=[C:30]([C:28]5[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=5)[CH:31]=4)=[N:41][CH:40]=3)[CH:46]=[N:45]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 21959416Tert-butyl 3-((methanesulfonyloxy)methyl)azetidine-1-carboxylateHCID 729446552-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine

Product 1

HCID 899242163-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-ylmethyl)-azetidine-1-carboxylic acid tert-butyl esterYield 131.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 3-Methanesulfonyloxymethyl-azetidine-1-carboxylic acid tert-butyl ester (Matrix scientific, 200 mg; 0.68 mmol; 1.0 eq.), cesium carbonate (442 mg; 1.36 mmol; 2.0 eq.) and 2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine (example 3, 205 mg; 0.68 mmol; 1.0 eq.) in dry DMA (3 mL) was heated at 100° C. O/N. The reaction mixture was then diluted with water and extracted with EtOAc (three times). Combined organic phases were washed with brine (three times), dried over magnesium sulfate, filtered and concentrated. The crude was dissolved in DMSO and precipitated by addition of acetonitrile. It was filtered, rinced with acetonitrile and dried under vacuum to give the title compound as a yellow powder (423 mg, quantitative). MS (ESI+): 472.3.

Workup

  1. extractionextracted with EtOAc (three times)
  2. washCombined organic phases were washed with brine (three times)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude was dissolved in DMSO
  7. customprecipitated by addition of acetonitrile
  8. filtrationIt was filtered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-a32e372364854ceaa587b05ccebc426b
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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