Dichloromethane → tert-butyl 4-(3-(6-(1H-1,2,4-triazol-1-yl)pyridin-3-yl)-7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate

HRID 2047134Notes

Reaction equation

HRID 2047134 reaction equation
[CH3:1][Si:2]([CH3:40])([CH3:39])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[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][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1.CC1(C)C(C)(C)OB([C:49]2[CH:50]=[CH:51][C:52]([N:55]3[CH:59]=[N:58][CH:57]=[N:56]3)=[N:53][CH:54]=2)O1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[N:55]1([C:52]2[N:53]=[CH:54][C:49]([C:16]3[CH:15]=[N:14][N:13]4[C:8]([N:7]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:40])([CH3:39])[CH3:1])=[CH:9][C:10]([CH:18]5[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]5)=[N:11][C:12]=34)=[CH:50][CH:51]=2)[CH:59]=[N:58][CH:57]=[N:56]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 592433295-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(1H-1,2,4-triazol-1-yl)pyridineHCID 66584511Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate

Product 1

HCID 67494194tert-butyl 4-(3-(6-(1H-1,2,4-triazol-1-yl)pyridin-3-yl)-7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylateYield 64.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a pressure tube were charged tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (563 mg, 0.8 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(1H-1,2,4-triazol-1-yl)pyridine (287 mg, 1.1 mmol), PdCl2(dppf)2.CH2Cl2 (29 mg, 0.04 mmol), DME (6 mL) and 2M Na2CO3 (2 mL). The resulting mixture was briefly degassed with Argon; the tube was capped, and heated with stirring under 80° C. overnight. After cooling, solvent was removed. The residue was diluted with EtOAc (20 ml), and organic layer was isolated, washed with brine and dried (MgSO4). After concentration under reduced pressure, the residue was purified on silica gel eluting with EtOAc/Hexanes (0-50%) to provide the title compound (370 mg, 64%).

Workup

  1. customThe resulting mixture was briefly degassed with Argon
  2. customthe tube was capped
  3. temperatureheated
  4. temperatureAfter cooling
  5. customsolvent was removed
  6. additionThe residue was diluted with EtOAc (20 ml)
  7. customorganic layer was isolated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationAfter concentration under reduced pressure
  11. customthe residue was purified on silica gel eluting with EtOAc/Hexanes (0-50%)

Sources & evidence

ORD record
ord-6bb25a6ca3594219b8fd8e2816159af2
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

Loading…