Potassium Phosphate, Tribasic → Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-(3-fluoro-4-methoxyphenyl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 2368972Notes

Reaction equation

HRID 2368972 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:21][Si:22]([CH3:68])([CH3:67])[CH2:23][CH2:24][O:25][CH2:26][N:27]([CH2:59][O:60][CH2:61][CH2:62][Si:63]([CH3:66])([CH3:65])[CH3:64])[C:28]1[N:33]2[N:34]=[CH:35][C:36]([C:37]3[CH:38]=[N:39][C:40](Cl)=[CH:41][CH:42]=3)=[C:32]2[N:31]=[C:30]([CH:44]2[CH2:50][CH:49]3[N:51]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH:46]([CH2:47][CH2:48]3)[CH2:45]2)[CH:29]=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].C(Cl)Cl>[CH3:66][Si:63]([CH3:64])([CH3:65])[CH2:62][CH2:61][O:60][CH2:59][N:27]([CH2:26][O:25][CH2:24][CH2:23][Si:22]([CH3:21])([CH3:68])[CH3:67])[C:28]1[N:33]2[N:34]=[CH:35][C:36]([C:37]3[CH:38]=[N:39][C:40]([C:4]4[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([F:1])[CH:3]=4)=[CH:41][CH:42]=3)=[C:32]2[N:31]=[C:30]([CH:44]2[CH2:50][CH:49]3[N:51]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH:46]([CH2:47][CH2:48]3)[CH2:45]2)[CH:29]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27821943-Fluoro-4-methoxyphenylboronic acidHCID 86674906Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 66584726Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-(3-fluoro-4-methoxyphenyl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

3-Fluoro-4-methoxyphenylboronic acid (2.79 mmol, 475.7 mg), K3PO4 (4.20 mmol, 890.4 mg), and PdCl2(dppf)-CH2Cl2 (0.14 mmol, 114.3 mg) were added to a solution of tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (1.40 mmol, 1000 mg) in dioxane (12 mL) and H2O (1.5 mL). The resulting solution was stirred at 150° C. under microwave condition for 1 h. The mixture was diluted with H2O and then extracted with ethyl acetate (×2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-(3-fluoro-4-methoxyphenyl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate, LCMS tR=3.31 Min (5 min run, UV254nm). Mass calculated for, M+H 805.42, observed LC/MS m/z 805.17 (M+H).

Workup

  1. extractionextracted with ethyl acetate (×2)
  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-636b1e0cdd584107b6002828cdc4d3d1
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

Loading…