Dimethylformamide → (R)-4-(1-(2-(1,3-dioxoisoindolin-2-yl)propyl)-1H-pyrazol-3-yl)-2-(trifluoromethyl)benzonitrile

HRID 872554Notes

Reaction equation

[NH:1]1[C:5]([C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:17])([F:16])[F:15])[CH:7]=2)=[CH:4][CH:3]=[N:2]1.Br[CH2:19][C@H:20]([N:22]1[C:30](=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]1=[O:32])[CH3:21].CN(C=O)C.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.CNCCNC.O>[O:32]=[C:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:30](=[O:31])[N:22]1[C@H:20]([CH3:21])[CH2:19][N:2]1[CH:3]=[CH:4][C:5]([C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:15])([F:16])[F:17])[CH:7]=2)=[N:1]1

Participants

Conditions

Temperature: 160 °C

Procedure

4-(1H-pyrazol-5-yl)-2-(trifluoromethyl)benzonitrile (1.0 g, 4.22 mmol) and (R)-2-(1-bromopropan-2-yl)isoindoline-1,3-dione (1.35 g, 5.06 mmol) were weighed into a microreaction vial and DMF (10 ml) was added. Then, potassium carbonate (1.165 g, 8.43 mmol), copper(I) iodide (0.040 g, 0.21 mmol) and N,N′-dimethyl-ethylenediamine (0.004 ml, 0.042 mmol) were added and the reaction vial was capped under nitrogen and was heated in the microwave oven (Biotage) at 160° C. for 30 min. The mixture was then poured into water and extracted with DCM and 2% MeOH/DCM. Organic layers were combined, dried with Na2SO4, filtered and evaporated to dryness. CombiFlash purifications using normal and reversed phase columns afforded 0.199 g of the title compound. 1H-NMR (400 MHz; d6-DMSO): δ 1.54 (m, 3H), 4.55-4.65 (m, 3H), 6.95 (d, 1H), 7.77 (m, 4H), 7.82 (m, 1H), 7.86-7.89 (m, 2H), 8.01 (d, 1H).

Workup

additionwas added
customthe reaction vial was capped under nitrogen
extractionextracted with DCM and 2% MeOH/DCM
dry with materialdried with Na2SO4
filtrationfiltered
customevaporated to dryness

Sources & evidence

ORD record: ord-6a37a0d9fb0944f78d224e7edf46c9bc
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975254B2

Reaction notes

Loading…