Cesium carbonate → HCID 89919584, compound

HRID 921801Notes

Reaction equation

HRID 921801 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:32]([Cl:33])=[CH:31][N:30]=[C:29]([C:34]#[N:35])[N:28]=1.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+]>O1CCOCC1.CCOC(C)=O>[Cl:33][C:32]1[C:27]([NH:26][C:2]2[N:7]=[C:6]([N:8]([CH:18]3[CH2:19][CH2:20]3)[CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[C:5]3=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]3[N:3]=2)=[N:28][C:29]([C:34]#[N:35])=[N:30][CH:31]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 717485704-Amino-5-chloropyrimidine-2-carbonitrileHCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile2×

Product 1

HCID 89919584HCID 89919584, compoundYield 15.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

2-Bromo-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 9) (168 mg, 0.421 mmol), 4-amino-5-chloropyrimidine-2-carbonitrile (65 mg, 0.421 mmol)Pd2(DBA)3 (77 mg, 0.084 mmol), xantphos (48.7 mg, 0.084 mmol) and cesium carbonate (274 mg, 0.841 mmol) were suspened in dioxane (4206 μl) at rt. The reaction was degassed using the vacuum/purge method (4 times) to put the reaction under N2. The reaction was heated to 70° C. for 4 h before cooling to room temperature, diluting with EtOAc, filtered through celite and concentrated. The crude product was purified by column chromatography (40 g SiO2, 0 to 100% EtOAc-hexane gradient elution) to afford 30 mg of 2-((5-Chloro-2-cyanopyrimidin-4-yl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Workup

  1. customThe reaction was degassed
  2. customthe reaction under N2
  3. temperaturebefore cooling to room temperature
  4. filtrationfiltered through celite
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (40 g SiO2, 0 to 100% EtOAc-hexane gradient elution)

Sources & evidence

ORD record
ord-4ee1a9cf2dc640bda9e7c1532e037551
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…