Potassium Phosphate, Tribasic → ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate

HRID 334367Notes

Reaction equation

HRID 334367 reaction equation
[CH3:1][Si:2]([CH3:40])([CH3:39])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:8]1[N:13]2[N:14]=[CH:15][C:16](I)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:23][CH2:22][C:21]([CH2:29][OH:30])([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1.[C:41]1([N:47]2[CH:51]=[C:50](B3OC(C)(C)C(C)(C)O3)[CH:49]=[N:48]2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH3:1][Si:2]([CH3:40])([CH3:39])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:50]3[CH:49]=[N:48][N:47]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH:51]=3)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:23][CH2:22][C:21]([CH2:29][OH:30])([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 569657711-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66583826Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate

Product 1

HCID 86686666ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylateYield 72.4%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A mixture of ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate (270 mg, 0.383 mmol), 1-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (135 mg, 0.498 mmol), PdCl2(dppf)CH2Cl2 (31.3 mg, 0.038 mmol), and K3PO4 (244 mg, 1.15 mmol) in dioxane/H2O (3/0.3 mL) was degassed and then heated at 90° C. for 16 h. After cooling, the reaction mixture was diluted with EtOAc and washed with H2O and brine, dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.55 in 50% EtOAc) to afford ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate as a pale yellow solid (200 mg). HPLC-MS TR=3.06 min (UV 254 nm, 5 min method); mass calculated for formula C37H56N6O5Si2 720.4, observed LCMS m/z 721.3 (M+H).

Workup

  1. customwas degassed
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.55 in 50% EtOAc)

Sources & evidence

ORD record
ord-8367c6ab44d349aabe7918f3d7e44f38
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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