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

HRID 2368997Notes

Reaction equation

HRID 2368997 reaction equation
[CH3:1][Si:2]([CH3:45])([CH3:44])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[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:31][CH2:32][CH2:33][O:34][CH3:35])([C:24]([O:26][CH2:27][CH2:28][O:29][CH3:30])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1.[C:46]1([N:52]2[CH:56]=[C:55](B3OC(C)(C)C(C)(C)O3)[CH:54]=[N:53]2)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH3:1][Si:2]([CH3:45])([CH3:44])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:55]3[CH:54]=[N:53][N:52]([C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)[CH:56]=3)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:23][CH2:22][C:21]([O:31][CH2:32][CH2:33][O:34][CH3:35])([C:24]([O:26][CH2:27][CH2:28][O:29][CH3:30])=[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 665836212-Methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate

Product 1

HCID 665837282-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylateYield 73%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
90 °C

Procedure

A mixture of 2-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate (3.06 g, 3.93 mmol), 1-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.38 g, 5.11 mmol), PdCl2(dppf)CH2Cl2 (321 mg, 0.393 mmol), and K3PO4 (2.50 g, 11.8 mmol) in dioxane/H2O (40/4 mL) was degassed and then heated at 90° C. for 16 h. LCMS showed very good conversion to the desired product (795), and about 10% de-iodination byproduct (653). 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=0.6 in 50% EtOAc/Hexanes) to afford 2-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate as a brown oil (2.28 g, 73%).

Workup

  1. customwas degassed
  2. additionThe reaction mixture was diluted with EtOAc
  3. washwashed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.6 in 50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-5abe845ab80b40ccbb788d709abee8f3
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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