Dichloromethane → HCID 67494490, compound

HRID 2047136Notes

Reaction equation

HRID 2047136 reaction equation
[CH3:1][Si:2]([CH3:46])([CH3:45])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20](Cl)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[CH:9]=1.[F:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1B(O)O.C(Cl)Cl.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.O.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]>[CH3:1][Si:2]([CH3:46])([CH3:45])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:49]4[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=4[F:47])=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[CH:9]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 27343542-Fluorophenylboronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 86664786HCID 86664786, compound

Product 1

HCID 67494490HCID 67494490, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (2.25 g, 3.3 mmol) in Dioxane (24 ml) and H2O (6 ml) was added the 2-fluorophenylboronic acid (0.92 g, 6.6 mmol), PdCl2(dppf)2.CH2Cl2 (0.32 g, 0.39 mmol) and K3PO4.H2O (1.7 g, 8.2 mmol). The reaction was heated at 100° C. for 16 hours, at which time LC/MS analysis confirmed full consumption of starting material. On cooling, H2O (100 ml) and EtOAc (100 ml) were added and organics were extracted with EtOAc (4×50 ml), dried (Na2SO4) and concentrated in vacuo to give a crude product. Gradient column chromatography on silica eluting with 0% to 100% EtOAc/hexanes gave tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-(2-fluorophenyl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (2.3 g, 95%).

Workup

  1. customconsumption of starting material
  2. temperatureOn cooling
  3. additionH2O (100 ml) and EtOAc (100 ml) were added
  4. extractionorganics were extracted with EtOAc (4×50 ml)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto give a crude product

Sources & evidence

ORD record
ord-2833b0be210b4ba2b4e13c0020c72149
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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