Ethyl Acetate → Methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetate

HRID 2047030Notes

Reaction equation

HRID 2047030 reaction equation
[CH3:1][Si:2]([CH3:39])([CH3:38])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:8]1[N:13]2[N:14]=[CH:15][C:16](I)=[C:12]2[N:11]=[C:10]([O:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][C:26]([O:28][CH3:29])=[O:27])=[CH:21][CH:20]=2)[CH:9]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1[CH2:53][CH2:52]OCC1.CCO[C:57]([CH3:59])=O>>[CH3:1][Si:2]([CH3:39])([CH3:38])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:16]3[CH:12]=[N:11][C:10]4[C:52]([CH:53]=3)=[CH:59][CH:57]=[CH:8][CH:9]=4)=[C:12]2[N:11]=[C:10]([O:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][C:26]([O:28][CH3:29])=[O:27])=[CH:21][CH:20]=2)[CH:9]=1

Participants

5

Reactant 4

HCID 8857Ethyl AcetateHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 66733474Methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetate

Product 1

HCID 66735130Methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetate

Conditions

Temperature
90 °C

Procedure

Under Ar, compound, methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetate (180 mg, 0.26 mmol) was mixed with Pd(dppf) Cl2 (21 mg, 0.26 mmol, K3PO4 (106 mg, 0.5 mmol), 3-quinoline bornic acid (55 mg, 0.31 mmol) and dioxane (10 mL with 1 ml water). The resulting mixture was heated at 90° C. and stirred over night. After cooled to room temperature, the mixture was diluted with EtOAc (60 mL) and filtered through celite. After concentration, the crude was purified with column (silica gel, 0˜30% EtOAc/Hexane) gave the product, methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetate (150 mg). HPLC-MS tR=2.60 min (UV254 nm); mass calculated for formula C36H47N5O5Si2 685.3, observed LCMS m/z 686.3 (M+H).

Workup

  1. temperatureAfter cooled to room temperature
  2. filtrationfiltered through celite
  3. concentrationAfter concentration
  4. customthe crude was purified with column (silica gel, 0˜30% EtOAc/Hexane)

Sources & evidence

ORD record
ord-162e2e2a76d648fe8180e638ba1cb46a
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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