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

HRID 1913263Notes

Reaction equation

HRID 1913263 reaction equation
[C:1]1([C:7]2[CH:12]=[CH:11][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.[CH3:33][Si:34]([CH3:73])([CH3:72])[CH2:35][CH2:36][O:37][CH2:38][N:39]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])[C:40]1[N:45]2[N:46]=[CH:47][C:48](I)=[C:44]2[N:43]=[C:42]([CH2:50][CH:51]2[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:53][CH2:52]2)[CH:41]=1>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]>[CH3:71][Si:68]([CH3:69])([CH3:70])[CH2:67][CH2:66][O:65][CH2:64][N:39]([CH2:38][O:37][CH2:36][CH2:35][Si:34]([CH3:33])([CH3:72])[CH3:73])[C:40]1[N:45]2[N:46]=[CH:47][C:48]([C:10]3[CH:9]=[N:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[CH:12][CH:11]=3)=[C:44]2[N:43]=[C:42]([CH2:50][CH:51]2[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:53][CH2:52]2)[CH:41]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 457865262-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 66733306Tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate

Product 1

HCID 67494549Tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.32 mmol, 370 mg), K3PO4 (3.04 mmol, 644 mg), and PdCl2(dppf).CH2Cl2 (0.10 mmol, 83 mg) was added to a solution of tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate (Int-12e, 1.02 mmol, 726 mg) in dioxane (6 mL) and H2O (1 mL). The resulting solution was stirred at 100° C. under argon for 18 hours. The mixture was diluted with H2O and then extracted with ethyl acetate (x2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate (Int-12f): LCMS tR=3.47 Min (5 min run, UV254nm). Mass calculated for, M+744.2, observed m/z 745.2 (M+H).

Workup

  1. extractionextracted with ethyl acetate (x2)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried with Na2SO4
  4. customEvaporation and purification by column chromatography

Sources & evidence

ORD record
ord-5a415a045d864814aeff3b3e168043f7
Source dataset
uspto-grants-2013_12
Patent number
US08609675B2

Reaction notes

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