Benzocaine → HCID 59618079, compound

HRID 449891Notes

Reaction equation

HRID 449891 reaction equation
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:30]=[CH:29][C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.O1CCOCC1>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:29][CH:30]=2)[CH:7]=1)=[O:18]

Participants

7

Reactant 3

HCID 2337BenzocaineHCID 10796Cesium carbonateHCID 75464886N-(2-Bromopyridin-4-yl)-2,6-dichlorobenzamide

Product 1

HCID 59618079HCID 59618079, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A 25 mL microwave tube containing N-(2-bromopyridin-4-yl)-2,6-dichlorobenzamide (0.50 g, 1.40 mmol), ethyl 4-aminobenzoate (0.31 g, 1.92 mmol), Pd2(dba)3 (40 mg, 0.043 mmol), Cs2CO3 (0.94 g, 2.91 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 17 mg, 0.029 mmol), and dioxane (20 mL) was degassed and then charged by N2 (3×). The mixture was then heated at 120° C. for 30 min and then diluted with dioxane (20 mL). The reaction was filtered through Celite and concentrated under reduced pressure. The residue was purified by reverse-phase HPLC (Gemini, 200 mm×25 mm, gradient: CH3CN/0.05% NH3.H2O, 50-80%, 10 min) to afford ethyl 4-(4-(2,6-dichlorobenzamido)pyridin-2-ylamino)benzoate (500 mg, yield: 80%). 1H NMR (400 MHz, DMSO) δ 11.02 (s, 1H), 9.60 (s, 1H), 8.15 (d, J=5.6, 1H), 7.96-7.76 (m, 4H), 7.57 (ddd, J=16.0, 9.0, 4.2, 4H), 6.92 (dd, J=5.6, 1.6, 1H), 4.27 (q, J=7.1, 2H), 1.31 (t, J=7.1, 3H). LCMS (ESI) m/z: 431.4 [M+H+].

Workup

  1. customwas degassed
  2. additioncharged by N2 (3×)
  3. additiondiluted with dioxane (20 mL)
  4. filtrationThe reaction was filtered through Celite
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by reverse-phase HPLC (Gemini, 200 mm×25 mm, gradient: CH3CN/0.05% NH3.H2O, 50-80%, 10 min)

Sources & evidence

ORD record
ord-22fe4a87b11648bcb400e74fe9a0d502
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

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