Cesium carbonate → HCID 178468908, compound

HRID 906177Notes

Reaction equation

HRID 906177 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[C:13]#[N:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6].CC([N:19]([C@H:23]1[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25][CH2:24]1)[C:20](=[O:22])[O-:21])(C)C.[CH3:30][C:31]1(C)[C:57]2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:32]1=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(OCC)(=O)C>[C:13]([C:12]1[CH:11]=[CH:10][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3][C:2]=1[NH:29][C@H:26]1[CH2:25][CH2:24][C@H:23]([NH:19][C:20]([O:21][C:31]([CH3:57])([CH3:32])[CH3:30])=[O:22])[CH2:28][CH2:27]1)#[N:14]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 18374323Ethyl 3-bromo-4-cyanobenzoateHCID 178449843HCID 178449843, compound

Product 1

HCID 178468908HCID 178468908, compoundYield 298.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of ethyl 3-bromo-4-cyanobenzoate (0.82 g, 3.24 mmol), 1,1-dimethylethyl(trans-4-aminocyclohexyl)carbamate (0.69 g, 3.24 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.148 g, 0.16 mmol), XANTPHOS (0.19 g, 0.32 mmol) and cesium carbonate (1.48 g, 4.54 mmol) in dioxane (13 mL) was refluxed for 15 hours. On cooling to room temperature, the mixture was filtered through Celite, concentrated, and purified by silica gel column chromatography using hexanes:ethyl acetate from 5:1 to 4:1 to afford ethyl 4-cyano-3-{[trans-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)cyclohexyl]amino}benzoate (0.370 g, 30% yield). 1H NMR (400 MHz, d6-DMSO): 7.59 (d, 1H), 7.28 (s, 1H), 7.13 (dd, 1H), 6.82 (d, 1H), 6.05 (d, 1H), 4.31 (q, 2H), 3.46-3.37 (m, 1H), 3.28-3.17 (m, 1H), 1.95-1.85 (m, 2H), 1.84-1.76 (m, 2H), 1.46, 1.22 (m, 16H).

Workup

  1. temperaturewas refluxed for 15 hours
  2. filtrationthe mixture was filtered through Celite
  3. concentrationconcentrated
  4. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-9463a1d75487433890ba5cf56f423ae1
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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