Cesium carbonate → HCID 89922862, compound

HRID 921847Notes

Reaction equation

HRID 921847 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[CH:28]=[C:29]([CH:32]=[C:33]([CH:36]([CH3:39])[CH2:37][OH:38])[C:34]=1[Cl:35])[C:30]#[N:31].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:35][C:34]1[C:33]([CH:36]([CH3:39])[CH2:37][OH:38])=[CH:32][C:29]([C:30]#[N:31])=[CH:28][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:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=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 89923317HCID 89923317, compound

Product 1

HCID 89922862HCID 89922862, compoundYield 59.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (42 mg, 0.118 mmol), 3-amino-4-chloro-5-(1-hydroxypropan-2-yl)benzonitrile (24.94 mg, 0.118 mmol), palladium(II) acetate (7.97 mg, 0.036 mmol), DPPF (6.56 mg, 0.012 mmol), Xantphos (6.85 mg, 0.012 mmol), and cesium carbonate (77 mg, 0.237 mmol) were combined in a 2 dram vial and dioxane (1.2 mL) was added. The vial was evacuated and backfilled with N2 3×, then heated at 100° C. for 1.5 h. The reaction was cooled to room temperature and filtered through celite, rinsing with EtOAc. The solvent was removed in vacuo and the material was purified by flash column chromatography (0-3% MeOH/DCM; 40 g column). 2-((2-chloro-5-cyano-3-(1-hydroxypropan-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (37 mg) was obtained as a yellow glass.

Workup

  1. customThe vial was evacuated
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through celite
  4. washrinsing with EtOAc
  5. customThe solvent was removed in vacuo
  6. customthe material was purified by flash column chromatography (0-3% MeOH/DCM; 40 g column)

Sources & evidence

ORD record
ord-6620b089e34a4763917e50a877ce9d49
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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