Cesium carbonate → HCID 86708673, compound

HRID 921780Notes

Reaction equation

HRID 921780 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N:9]([CH3:20])[CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[C:4]([C:21]#[N:22])[CH:3]=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+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>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].CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:8][C:7]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:3][C:4]([C:21]#[N:22])=[C:5]([N:9]([CH3:20])[CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:16])[CH3:17])[CH:6]=1

Participants

7

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-carbonitrile2×HCID 86708671HCID 86708671, compound

Product 1

HCID 86708673HCID 86708673, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl (2-((4-amino-5-chloro-2-cyanophenyl)(methyl)amino)ethyl)carbamate (207 mg, 0.637 mmol), 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 9)(226 mg, 0.637 mmol), Cs2CO3 (415 mg, 1.28 mmol), DPPF (35.3 mg, 0.064 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyxanthene (36.9 mg, 0.064 mmol), and Pd(OAc)2 (42.9 mg, 0.191 mmol) in a microwave vial was flushed with nitrogen. Dioxane (9 mL) was added and the vial was sealed and heated at 100° C. for 4 hr. The reaction was diluted with EtOAc and filtered through celite. The solvent was removed and radial silica gel chromatography with hexane containing 5 to 40% EtOAc afforded tert-butyl (2-((5-chloro-2-cyano-4-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2 yl)amino)phenyl)(methyl)amino)ethyl)carbamate (283 mg) as an oil.

Workup

  1. customwas flushed with nitrogen
  2. additionDioxane (9 mL) was added
  3. customthe vial was sealed
  4. additionThe reaction was diluted with EtOAc
  5. filtrationfiltered through celite
  6. customThe solvent was removed

Sources & evidence

ORD record
ord-166a7c471c884c38b49b99d1e467d42c
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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