Carbonate Ion → 4-chloro-1-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidine

HRID 1931595Notes

Reaction equation

C(=O)([O-])[O-].FC(F)(F)C(O)=O.[CH:12]([C:15]1[N:19]=[C:18]([N:20]2[CH2:25][CH2:24][CH:23]([NH:26][NH2:27])[CH2:22][CH2:21]2)[O:17][N:16]=1)([CH3:14])[CH3:13].[Cl:28][C:29]1[C:34]([CH:35]=O)=[C:33](Cl)[N:32]=[CH:31][N:30]=1>C(#N)C>[Cl:28][C:29]1[N:30]=[CH:31][N:32]=[C:33]2[N:26]([CH:23]3[CH2:24][CH2:25][N:20]([C:18]4[O:17][N:16]=[C:15]([CH:12]([CH3:14])[CH3:13])[N:19]=4)[CH2:21][CH2:22]3)[N:27]=[CH:35][C:34]=12

Participants

Conditions

Temperature: 140 °C

Procedure

SiliaBond Carbonate (Silicycle, Quebec City, Canada; 0.69 mmol/g loading; 395 mg, 0.27 mmol) was added to a mixture of [1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-hydrazine trifluoroacetic acid salt (from Step 4; 185 mg, 0.55 mmol) and 4,6-dichloro-pyrimidine-5-carbaldehyde (Intermediate 16; 81 mg, 0.45 mmol) in anhydrous acetonitrile (3 mL). The reaction mixture was heated in a Biotage Optimizer microwave at 140° C. for 5 min. The resin was filtered off and washed with acetonitrile. The solvent was evaporated and the residue was purified on a silica column (ISCO 12 g) eluting with 0-3% methanol/dichloromethane to give 4-chloro-1-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidine (31 mg, 20%). Mass spectrum (ES) MH+=348.

Workup

filtrationThe resin was filtered off
washwashed with acetonitrile
customThe solvent was evaporated
customthe residue was purified on a silica column (ISCO 12 g)
washeluting with 0-3% methanol/dichloromethane

Sources & evidence

ORD record: ord-cac74b3b5ae04e158a66679beac0e1e6
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188098B2

Reaction notes

Loading…