Cesium carbonate → HCID 131732400, compound

HRID 921740Notes

Reaction equation

HRID 921740 reaction equation
[CH2:1]([N:3]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[C:4]1[C:9]2=[N:10][CH:11]=[C:12]([C:13]#[N:14])[N:8]2[N:7]=[C:6](S(C)(=O)=O)[N:5]=1)[CH3:2].[NH2:28][C:29]1[C:30]([F:49])=[C:31]([N:37]2[CH2:42][CH2:41][C@@H:40]([NH:43][C:44](=[O:47])[O:45][CH3:46])[C@H:39]([OH:48])[CH2:38]2)[CH:32]=[C:33]([C:35]#[N:36])[CH:34]=1.C([O-])([O-])=O.[Cs+].[Cs+].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>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.O1CCOCC1>[C:35]([C:33]1[CH:34]=[C:29]([NH:28][C:6]2[N:5]=[C:4]([N:3]([CH2:1][CH3:2])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[C:9]3=[N:10][CH:11]=[C:12]([C:13]#[N:14])[N:8]3[N:7]=2)[C:30]([F:49])=[C:31]([N:37]2[CH2:42][CH2:41][C@@H:40]([NH:43][C:44](=[O:47])[O:45][CH3:46])[C@H:39]([OH:48])[CH2:38]2)[CH:32]=1)#[N:36]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86708602HCID 86708602, compound2×HCID 131732401HCID 131732401, compound

Product 1

HCID 131732400HCID 131732400, compoundYield 66.9%

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-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 7)(50 mg, 0.146 mmol), methyl ((3R,4R)-1-(3-amino-5-cyano-2-fluorophenyl)-3-hydroxypiperidin-4-yl)carbamate (46 mg, 0.149 mmol), DPPF (5.66 mg, 10.21 μmol), Cs2CO3 (81 mg, 0.248 mmol), Xantphos (8.44 mg, 0.015 mmol), Palladium(II)Acetate (9.82 mg, 0.044 mmol) and 1,4-dioxane (2 ml) were combined in a microwave vial. The vial was evacuated and backfilled with Nitrogen 3×. The reaction stirred at 100° C. for 3 hr. The reaction mixture cooled to 25° C., diluted with EtOAc and washed with brine and dried (Na2SO4). The solvents were removed and the material purified on silica gel 25% EtOAc in DCM to afford methyl ((3R,4R)-1-(5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-2-fluorophenyl)-3-hydroxypiperidin-4-yl)carbamate (60 mg)

Workup

  1. customThe vial was evacuated
  2. temperatureThe reaction mixture cooled to 25° C.
  3. additiondiluted with EtOAc
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. customThe solvents were removed
  7. customthe material purified on silica gel 25% EtOAc in DCM

Sources & evidence

ORD record
ord-cb86e7b51efe433cbe02b3a63d5ae8e1
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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