2-Methyl-4-methoxyaniline → {3-[4-(2-Methoxybenzyloxy)-benzenesulfonyl]-6-methylpyridin-2-yl}-(4-methoxy-2-methylphenyl)-amine

HRID 1796325Notes

Reaction equation

HRID 1796325 reaction equation
Br[C:2]1[C:7]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][CH3:26])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:6][CH:5]=[C:4]([CH3:27])[N:3]=1.[CH3:28][C:29]1[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:30]=1[NH2:31].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CCOCC>[CH3:26][O:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([S:8]([C:7]2[C:2]([NH:31][C:30]3[CH:32]=[CH:33][C:34]([O:36][CH3:37])=[CH:35][C:29]=3[CH3:28])=[N:3][C:4]([CH3:27])=[CH:5][CH:6]=2)(=[O:10])=[O:9])=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 76102-Methyl-4-methoxyanilineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 221816842-Bromo-3-[4-(2-methoxybenzyloxy)-benzenesulfonyl]-6-methylpyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 9914082{3-[4-(2-Methoxybenzyloxy)-benzenesulfonyl]-6-methylpyridin-2-yl}-(4-methoxy-2-methylphenyl)-amineYield 15%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

2-Bromo-3-[4-(2-methoxybenzyloxy)-benzenesulfonyl]-6-methylpyridine from part F (75 mg, 0.167 mmol), 2-methyl-4-methoxyaniline (26 μL, 0.200 mmol), Pd(dba)3 (3 mg, 0.0033 mmol), dppp (3 mg, 0.0067 mmol), and NaOt-Bu (22 mg, 0.234 mmol) were suspended in toluene in a tightly capped conical vial. The reaction mixture was heated at 70° C. for 4.5 h. The mixture was cooled to rt, and diluted with ether. The organic layer was washed with brine (2×), dried over MgSO4, filtered, and concentrated. Purified by preparative TLC (1000 μM silica gel plate, 15% ethyl acetate in hexanes) to furnish the desired product (13 mg, 15% yield) as a pale yellow solid: mp 70–72° C.; 1H NMR (300 MHz, CDCl3) δ 8.31 (s, 1H), 7.93 (d, J=8.0 Hz, 1H), 7.77 (d, J=9.2 Hz, 2H), 7.52 (d, J=8.4 Hz, 1H), 7.30–7.22 (m, 2H), 6.96 (d, J=8.8 Hz, 2H), 6.90 (d, J=7.6 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 6.68 (d, J=9.1 Hz, 2H), 6.53 (d, J=8.0 Hz, 1H), 5.23 (s, 2H), 3.78 (s, 3H), 3.73 (s, 3H), 2.27 (s, 3H), 2.10 (s, 3H); HRMS (ESI) m/z 505.1807 [(M+H)+, calcd for C28H29N2O5S, 505.1797].

Workup

  1. temperatureThe mixture was cooled to rt
  2. washThe organic layer was washed with brine (2×)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurified by preparative TLC (1000 μM silica gel plate, 15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1e68c8aca85a431fa0c3661d2d41511d
Source dataset
uspto-grants-2006_04
Patent number
US07030145B2

Reaction notes

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