Potassium Phosphate, Tribasic → Ethyl 1-(benzyloxymethyl)-4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohex-3-enecarboxylate

HRID 334364Notes

Reaction equation

HRID 334364 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=1.[CH2:28]([O:35][CH2:36][C:37]1([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:42][CH2:41][C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH2:38]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH2:28]([O:35][CH2:36][C:37]1([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:42][CH2:41][C:40]([C:2]2[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]3[N:25]=[CH:26][CH:27]=[C:4]3[N:3]=2)=[CH:39][CH2:38]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 772312195-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amineHCID 86686665Ethyl 1-(benzyloxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate

Product 1

HCID 86686664Ethyl 1-(benzyloxymethyl)-4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohex-3-enecarboxylateYield 65.8%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
90 °C

Procedure

A mixture of 5-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (2.99 g, 6.97 mmol), ethyl 1-(benzyloxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (8.36 mmol), PdCl2(dppf)CH2Cl2 (683 mg, 0.836 mmol), and K3PO4 (5.32 g, 25.1 mmol) in dioxane/H2O (40/2 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 (0-20% EtOAc/Hexanes, Rf=0.45 in 20% EtOAc) to afford ethyl 1-(benzyloxymethyl)-4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohex-3-enecarboxylate as a pale yellow oil (3.06 g). HPLC-MS TR=3.17 min (UV 254 nm, 5 min method); mass calculated for formula C35H54N4O5Si2 666.4, observed LCMS m/z 667.3 (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 (0-20% EtOAc/Hexanes, Rf=0.45 in 20% EtOAc)

Sources & evidence

ORD record
ord-141f401b85224b52a8cba8c40628e6e8
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

Loading…