Acetamide → HCID 86270222, compound

HRID 2279034Notes

Reaction equation

HRID 2279034 reaction equation
[Cl:1][C:2]1[C:3]([O:24][C:25]2[CH:30]=[CH:29][N:28]=[C:27](Cl)[CH:26]=2)=[CH:4][C:5]([F:23])=[C:6]([NH:8][C:9]([N:11]2[CH2:15][CH2:14][N:13]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:12]2=[O:22])=[O:10])[CH:7]=1.[C:32]([NH2:35])(=[O:34])[CH3:33].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>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:32]([NH:35][C:27]1[CH:26]=[C:25]([O:24][C:3]2[C:2]([Cl:1])=[CH:7][C:6]([NH:8][C:9]([N:11]3[CH2:15][CH2:14][N:13]([CH:16]4[CH2:17][CH2:18][O:19][CH2:20][CH2:21]4)[C:12]3=[O:22])=[O:10])=[C:5]([F:23])[CH:4]=2)[CH:30]=[CH:29][N:28]=1)(=[O:34])[CH3:33]

Participants

7

Reactant 4

HCID 178AcetamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90426423HCID 90426423, compound

Product 1

HCID 86270222HCID 86270222, compoundYield 29%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of Example C8 (0.243 g, 0.518 mmol), acetamide (0.184 g, 3.11 mmol), Cs2CO3 (0.422 g, 1.294 mmol) and Xantphos (0.090 g, 0.155 mmol) in dioxane (3 mL) was sparged with Ar, treated with Pd2(dba)3 (0.062 g, 0.067 mmol), sparged again with Ar and heated at 100° C. overnight. The mixture was cooled to RT, treated with brine, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM, then MeOH/EtOAc) to afford N-(4-((2-acetamidopyridin-4-yl)oxy)-5-chloro-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (74 mg, 29%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (d, J=2.7 Hz, 1 H), 10.57 (s, 1 H), 8.39 (d, J=8.1 Hz, 1 H), 8.17 (d, J=5.7 Hz, 1 H), 7.61 (d, J=2.4 Hz, 1 H), 7.58 (d, J=11.2 Hz, 1 H), 6.64 (dd, J=5.7, 2.4 Hz, 1 H), 3.93-3.83 (m, 3 H), 3.81 (m, 2 H), 3.48 (t, J=8.2 Hz, 2 H), 3.37 (dd, J=12.4, 10.6 Hz, 2 H), 2.03 (s, 3 H), 1.71 (qd, J=12.2, 4.5 Hz, 2 H), 1.62-1.56 (m, 2H); MS (ESI) m/z: 492.1 (M+H+).

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with brine
  4. extractionextracted with EtOAc (3×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified twice via silica gel chromatography (MeOH/DCM

Sources & evidence

ORD record
ord-74261cb099184a75b38bae83c0514a87
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

Loading…