Cesium carbonate → HCID 89922656, compound

HRID 921890Notes

Reaction equation

HRID 921890 reaction equation
[NH2:1][C:2]1[C:3]([Cl:22])=[C:4]([C:10]2([OH:21])[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]2)[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.Cl[C:24]1[N:29]=[C:28]([N:30]([CH:40]2[CH2:42][CH2:41]2)[CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[C:27]2=[N:43][CH:44]=[C:45]([C:46]#[N:47])[N:26]2[N:25]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:22][C:3]1[C:2]([NH:1][C:24]2[N:29]=[C:28]([N:30]([CH:40]3[CH2:42][CH2:41]3)[CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=3)[C:27]3=[N:43][CH:44]=[C:45]([C:46]#[N:47])[N:26]3[N:25]=2)=[CH:7][C:6]([C:8]#[N:9])=[CH:5][C:4]=1[C:10]1([OH:21])[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:11]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileHCID 89922785HCID 89922785, compound

Product 1

HCID 89922656HCID 89922656, compoundYield 54.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 3-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxyazetidine-1-carboxylate (Example 647B) (37.4 mg, 0.116 mmol), 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (49.2 mg, 0.139 mmol), DPPF (6.40 mg, 0.012 mmol), Cs2CO3 (75 mg, 0.231 mmol), XANTPIIOS (6.68 mg, 0.012 mmol), and palladium(II) acetate (7.78 mg, 0.035 mmol) in a microwave vial in dioxane (1 mL) was evacuated and backfilled with nitrogen for 3 times, then the mixture was heated in an oil bath at 100° C. for 3 hours. The reaction mixture was diluted with EtOAc, washed with water, brine, and dried over Na2SO4. Removal of the solvent and the crude material was purified by radial silica gel chromatography eluting with hexane containing 10 to 40% EtOAc to afford 40.5 mg of tert-butyl 3-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxyazetidine-1-carboxylate

Workup

  1. customwas evacuated
  2. additionThe reaction mixture was diluted with EtOAc
  3. washwashed with water, brine
  4. dry with materialdried over Na2SO4
  5. customRemoval of the solvent
  6. customthe crude material was purified by radial silica gel chromatography
  7. washeluting with hexane containing 10 to 40% EtOAc

Sources & evidence

ORD record
ord-cfea4898cda64b6196da0f87d27da493
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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