Dichloromethane → 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

HRID 589159

Reaction equation

HRID 589159 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.[CH3:28][Si:29]([CH3:69])([CH3:68])[CH2:30][CH2:31][O:32][CH2:33][N:34]([CH2:60][O:61][CH2:62][CH2:63][Si:64]([CH3:67])([CH3:66])[CH3:65])[C:35]1[N:40]2[N:41]=[CH:42][C:43](I)=[C:39]2[N:38]=[C:37]([CH:45]2[CH2:51][CH:50]3[N:52]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH:47]([CH2:48][CH2:49]3)[CH2:46]2)[CH:36]=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]>[CH3:67][Si:64]([CH3:65])([CH3:66])[CH2:63][CH2:62][O:61][CH2:60][N:34]([CH2:33][O:32][CH2:31][CH2:30][Si:29]([CH3:28])([CH3:69])[CH3:68])[C:35]1[N:40]2[N:41]=[CH:42][C:43]([C:5]3[CH:4]=[N:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[C:39]2[N:38]=[C:37]([CH:45]2[CH2:51][CH:50]3[N:52]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH:47]([CH2:48][CH2:49]3)[CH2:46]2)[CH:36]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 27947192-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 67294720Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 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

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
70 °C

Procedure

2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (5.55 mmol, 1327 mg), K3PO4 (14.48 mmol, 3070 mg), and PdCl2(dppf).CH2Cl2 (0.48 mmol, 394 mg) were added to a solution of tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (1.98 mmol, 1101 mg) in dioxane (40 mL) and H2O (4 mL). The resulting solution was stirred at 70° C. under argon overnight. 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-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate, LCMS tR=3.29 Min (5 min run, UV254nm, Mass calculated for M+H 715.35, observed LC/MS m/z 715.02 (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-73be0a045965408a844d78f99ffff76e
Source dataset
uspto-grants-2016_01
Patent number
US09227971B2

Linked notes

Loading…