Potassium Phosphate, Tribasic → 4-(7-(Bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone

HRID 334360Notes

Reaction equation

HRID 334360 reaction equation
[CH3:1][Si:2]([CH3:34])([CH3:33])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[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](=[O:24])[CH2:20][CH2:19]2)[CH:9]=1.[C:35]1([C:41]2[CH:46]=[CH:45][C:44](B3OC(C)(C)C(C)(C)O3)=[CH:43][N:42]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH3:1][Si:2]([CH3:34])([CH3:33])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:44]3[CH:43]=[N:42][C:41]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:46][CH:45]=3)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[CH:9]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457865262-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 665836524-(7-(Bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone

Product 1

HCID 665838044-(7-(Bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanoneYield 81.8%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone (751 mg, 1.22 mmol), 2-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (444 mg, 1.58 mmol), PdCl2(dppf)CH2Cl2 (99.6 mg, 0.122 mmol), and K3PO4 (777 mg, 3.66 mmol) in dioxane/H2O (7/0.7 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=0.2 in 20% EtOAc/Hexanes) to afford 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone as a pale yellow solid (643 mg). HPLC-MS TR=3.12 min (UV 254 nm, 5 min method); mass calculated for formula C35H49N5O3Si2 643.3, observed LCMS m/z 644.2 (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=0.2 in 20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-763f5f839fa14d4e841c4d01182a2715
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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