Water → 3,5-Dimethoxy-4-methyl-N-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-2-phenylamino-benzyl]-benzamide

HRID 1296743Notes

Reaction equation

HRID 1296743 reaction equation
[NH2:1][C:2]1[CH:22]=[C:21]([C:23]2[N:27]=[C:26]([CH3:28])[O:25][N:24]=2)[CH:20]=[CH:19][C:3]=1[CH2:4][NH:5][C:6](=[O:18])[C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([CH3:15])=[C:9]([O:16][CH3:17])[CH:8]=1.Br[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[OH-].[K+].O>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.C1(C)C=CC=CC=1.[Pd]>[CH3:17][O:16][C:9]1[CH:8]=[C:7]([CH:12]=[C:11]([O:13][CH3:14])[C:10]=1[CH3:15])[C:6]([NH:5][CH2:4][C:3]1[CH:19]=[CH:20][C:21]([C:23]2[N:27]=[C:26]([CH3:28])[O:25][N:24]=2)=[CH:22][C:2]=1[NH:1][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:18]

Participants

8

Reactant 4

HCID 962WaterHCID 7961BromobenzeneHCID 14797Potassium HydroxideHCID 69491883N-[2-Amino-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzyl]-3,5-dimethoxy-4-methyl-benzamide

Product 1

HCID 694915483,5-Dimethoxy-4-methyl-N-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-2-phenylamino-benzyl]-benzamideYield 40.3%

Reagents, catalysts & solvents 3

HCID 5974Hexadecyltrimethylammonium BromideCatalyst2×HCID 23938PalladiumCatalyst3×HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of Pd(P(t-Bu3)2 (3.3 mg, 0.0065 mmol) and cetyltrimethylammonium bromide (1.2 mg, 0.0033 mmol) in toluene (2 mL) was added compound 1g (250 mg, 0.65 mmol), bromobenzene (0.072 mL, 0.68 mmol), potassium hydroxide (55 mg, 0.98 mmol), and water (0.018 mL, 0.98 mmol). The reaction mixture was heated at 90° C. for 24 h. Additional Pd(P(t-Bu3)2 (5 mg) and cetyltrimethyl-ammonium bromide (3 mg) was added and heating was continued for 18 h. Additional Pd(P(t-Bu3)2 (5 mg) was added, and the reaction was heated to 100° C. for 12 h. The reaction mixture was filtered through a column of silica gel in ethyl acetate and concentrated on a rotary evaporator. The residue was purified by chromatography on silica gel (30-40% v/v ethyl acetate/hexane) to give compound 8a (120 mg, 40%) as a colorless solid. ESI-MS m/e 459.2 (M+1).

Workup

  1. temperatureheating
  2. temperaturethe reaction was heated to 100° C. for 12 h
  3. filtrationThe reaction mixture was filtered through a column of silica gel in ethyl acetate
  4. concentrationconcentrated on a rotary evaporator
  5. customThe residue was purified by chromatography on silica gel (30-40% v/v ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c2b523ad2ef54138991ac8fc6aed2a81
Source dataset
uspto-grants-2007_07
Patent number
US07247654B2

Reaction notes

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