Potassium Phosphate, Tribasic → Pyridin-3-ylmethyl{[4-({[6-chloro-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)pyridin-2-yl]amino}carbonyl)phenyl]methyl}carbamate

HRID 1256658Notes

Reaction equation

HRID 1256658 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][O:8][C:9](=[O:21])[NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([NH2:20])=[O:19])=[CH:14][CH:13]=2)[CH:2]=1.CC([N:26]([C:30]1[C:31](Cl)=[N:32][C:33]([Cl:36])=[CH:34][CH:35]=1)[C:27](=[O:29])[O-:28])(C)C.[CH3:38][C:39]1(C)[C:65]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:40]1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.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]>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][O:8][C:9](=[O:21])[NH:10][CH2:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]([NH:20][C:31]3[C:30]([NH:26][C:27]([O:28][C:39]([CH3:65])([CH3:40])[CH3:38])=[O:29])=[CH:35][CH:34]=[C:33]([Cl:36])[N:32]=3)=[O:19])=[CH:16][CH:17]=2)[CH:2]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57745589HCID 57745589, compoundHCID 1317306211,1-Dimethylethyl(2,6-dichloropyridin-3-yl)carbamate

Product 1

HCID 59627859Pyridin-3-ylmethyl{[4-({[6-chloro-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)pyridin-2-yl]amino}carbonyl)phenyl]methyl}carbamate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A solution of pyridin-3-ylmethyl{[4-(aminocarbonyl)phenyl]methyl}carbamate (0.2 g, 0.70 mmol), 1,1-dimethylethyl(2,6-dichloropyridin-3-yl)carbamate (0.18 g, 0.70 mmol), Pd2(dba)3 (32 mg, 0.035 mmol), Xantphos (41 mg, 0.07 mmol) and K3PO4 (0.45 g, 2.1 mmol) in dioxane (3 mL) was degassed with nitrogen, sealed and heated to 100° C. for 14 hours. The reaction was diluted with ethyl acetate (50 mL), filtered through Celite and evaporated in vacuo. Purification by flash chromatography (0-3% methanol/DCM) gave pyridin-3-ylmethyl{[4-({[6-chloro-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)pyridin-2-yl]amino}carbonyl)phenyl]methyl}carbamate. MS: cal'd 512 (MH+), exp 512 (MH+).

Workup

  1. customsealed
  2. filtrationfiltered through Celite
  3. customevaporated in vacuo
  4. customPurification by flash chromatography (0-3% methanol/DCM)

Sources & evidence

ORD record
ord-a860497769c34f648926b060c6442e18
Source dataset
uspto-grants-2013_06
Patent number
US08461189B2

Reaction notes

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