Trifluoroacetic acid → 1-(1,4-dioxaspiro[4.5]dec-8-yl)-6-(1H-indol-5-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 1093162Notes

Reaction equation

HRID 1093162 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH:11]3[CH2:20][CH2:19][C:14]4([O:18][CH2:17][CH2:16][O:15]4)[CH2:13][CH2:12]3)[N:9]=[CH:10][C:5]2=[C:4]([N:21]2[CH2:27][CH:26]3[O:28][CH:23]([CH2:24][CH2:25]3)[CH2:22]2)[N:3]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[C:39]3[C:43](=[CH:44][CH:45]=2)[NH:42][CH:41]=[CH:40]3)O1.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O>CC#N.O.C(O)C.C1(C)C=CC=CC=1>[O:18]1[C:14]2([CH2:19][CH2:20][CH:11]([N:8]3[C:6]4=[N:7][C:2]([C:37]5[CH:38]=[C:39]6[C:43](=[CH:44][CH:45]=5)[NH:42][CH:41]=[CH:40]6)=[N:3][C:4]([N:21]5[CH2:27][CH:26]6[O:28][CH:23]([CH2:24][CH2:25]6)[CH2:22]5)=[C:5]4[CH:10]=[N:9]3)[CH2:12][CH2:13]2)[O:15][CH2:16][CH2:17]1

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 27347725-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 601675223-(6-chloro-1-(1,4-dioxaspiro[4.5]decan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

Product 1

HCID 574246471-(1,4-dioxaspiro[4.5]dec-8-yl)-6-(1H-indol-5-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidineYield 25%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

6-Chloro-1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidine (0.20 g, 0.493 mmol) is treated with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (0.119 g, 0.74 mmol), aq. Na2CO3 (0.52 mL, 2M), and tetrakis triphenylphosphine palladium (20 mg) in 1:1 toluene:ethanol. The reaction mixture is heated in a microwave at 120 C for 60 min. Aq. workup followed by RP HPLC (H2O, CH3CN, TFA) gives the title compound as a white solid (60 mg). MS m/s=487.2 (M+H)

Workup

  1. temperatureThe reaction mixture is heated in a microwave at 120 C for 60 min

Sources & evidence

ORD record
ord-9758579c52854634aa5fd1bba552e92b
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

Loading…