Cesium carbonate → HCID 118114785, compound

HRID 1050520Notes

Reaction equation

HRID 1050520 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:10]2[CH2:15][CH2:14][CH2:13][C@@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]2)[CH:5]=[N:6][C:7]=1[C:8]#[N:9].[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[O:32])=[CH:27][CH:26]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:8]([C:7]1[N:6]=[CH:5][C:4]([N:10]2[CH2:15][CH2:14][CH2:13][C@@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]2)=[CH:3][C:2]=1[NH:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]([N:33]2[CH2:34][CH2:35][O:36][CH2:37][CH2:38]2)=[O:32])=[CH:29][CH:30]=1)#[N:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5778154-(Morpholine-4-carbonyl)anilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 118115158HCID 118115158, compound

Product 1

HCID 118114785HCID 118114785, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of (R)-tert-butyl 1-(5-bromo-6-cyanopyridin-3-yl)piperidin-3-ylcarbamate (95) (300 mg, 0.78 mmol), (4-aminophenyl)(morpholino)methanone (322 mg, 1.56 mmol), Pd2(dba)3 (73 mg, 0.08 mmol), XantPhos (93 mg, 0.16 mmol), fine powder Cs2CO3 (765 mg, 2.34 mmol) in dioxane (50 mL) was degassed with nitrogen stream for 3 min. The mixture was stirred in a nitrogen atmosphere at 115° C. for 2 h. The mixture was cooled, diluted with 200 mL EtOAc, filtered through celite, and concentrated in vacuo. The residue was subjected to flash column chromatography with 20 to 100% EtOAc in DCM to isolate (R)-tert-butyl 1-(6-cyano-5-(4-(morpholine-4-carbonyl)phenylamino)pyridin-3-yl)piperidin-3-ylcarbamate (96) (yield >80%).

Workup

  1. customwas degassed with nitrogen stream for 3 min
  2. temperatureThe mixture was cooled
  3. additiondiluted with 200 mL EtOAc
  4. filtrationfiltered through celite
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-69117334a49244658540f956489cf8c6
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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