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 334357Notes

Reaction equation

HRID 334357 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. 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). HPLC-MS TR=3.25 min (UV 254 nm, 5 min method); mass calculated for formula C40H62N6O7Si2 794.4, observed LCMS m/z 795.3 (M+H).

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-b44dd29b6c0444b1b71857ad32f4f2f7
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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