Cesium carbonate → HCID 89922506, compound

HRID 921925Notes

Reaction equation

HRID 921925 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1.[NH2:26][C:27]1[C:28]([Cl:40])=[CH:29][C:30]([CH2:35][CH2:36][C:37](=[O:39])[CH3:38])=[C:31]([CH:34]=1)[C:32]#[N:33].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.[Fe+2].O1CCOCC1>[Cl:40][C:28]1[CH:29]=[C:30]([CH2:35][CH2:36][C:37](=[O:39])[CH3:38])[C:31]([C:32]#[N:33])=[CH:34][C:27]=1[NH:26][C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:19][CH2:20]2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileHCID 89922494HCID 89922494, compound

Product 1

HCID 89922506HCID 89922506, compoundYield 75.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (150 mg, 0.423 mmol), 5-amino-4-chloro-2-(3-oxobutyl)benzonitrile (104 mg, 0.465 mmol), palladium (II) acetate (28.5 mg, 0.127 mmol), DPPF (23.4 mg, 0.042 mmol), Xantphos (24.5 mg, 0.042 mmol), and cesium carbonate (207 mg, 0.643 mmol) were combined in a 20 dram vial and dioxane (2 mL) was added. The vial was evacuated and backfilled with N2 3×, then heated at 90° C. for 1.5 h. The reaction was cooled to room temperature and the reaction mixture was filtered through celite, rinsing with EtOAc. The solvent was removed in vacuo and the material was purified by ISCO Companion (0-100% EtOAc/Hexane). 2-((2-chloro-5-cyano-4-(3-oxobutyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl) amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (172 mg) was obtained as a yellow foam.

Workup

  1. customThe vial was evacuated
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationthe reaction mixture was filtered through celite
  4. washrinsing with EtOAc
  5. customThe solvent was removed in vacuo
  6. customthe material was purified by ISCO Companion (0-100% EtOAc/Hexane)

Sources & evidence

ORD record
ord-c2b6b40315db436a8dcf38e928488163
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…