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

HRID 1505708Notes

Reaction equation

HRID 1505708 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([CH2:13]OS(C)(=O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:25][N:26]1[CH:30]=[C:29]([C:31]2[CH:32]=[C:33]([C:37]3[N:42]=[CH:41][C:40]([C:43]4[CH:44]=[N:45][NH:46][CH:47]=4)=[CH:39][N:38]=3)[CH:34]=[CH:35][CH:36]=2)[CH:28]=[N:27]1>O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([CH2:13][N:45]2[CH:44]=[C:43]([C:40]3[CH:39]=[N:38][C:37]([C:33]4[CH:34]=[CH:35][CH:36]=[C:31]([C:29]5[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=5)[CH:32]=4)=[N:42][CH:41]=3)[CH:47]=[N:46]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 4183641tert-Butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 729446552-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine

Product 1

HCID 899243953-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 57.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 3-Methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (prepared as described in WO2010100144; 200 mg; 0.64 mmol; 1.0 eq.), cesium carbonate (420 mg; 1.29 mmol; 2.0 eq.) and 2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine (example 3, 195 mg; 0.64 mmol; 1.0 eq.) 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. Purification by autopreparative LC/MS afforded the title compound as a white foam (179 mg, 57%). MS (ESI+): 486.5.

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. customPurification by autopreparative LC/MS

Sources & evidence

ORD record
ord-368929df144c4b02a7090b4bcb31e4d8
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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