4-Chloroaniline → 1-(4-Chlorophenylamino)-4-(4-pyridylmethoxy)pyridazine

HRID 1070536Notes

Reaction equation

Br[N:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[CH:4][NH:3]1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1.C(OC(C)(C)C)(C)(C)C.[Na]>C1(C)C=CC=CC=1.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]>[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH:21][N:2]2[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=3)=[CH:4][NH:3]2)=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To 1-bromo-4-(4-pyridylmethoxy)pyridazine (50 mg, 0.19 mmol) in toluene (3 mL) was added 4-chloroaniline (29 mg, 0.22 mmol), catalytical amount of (R)-(+)2,2′-bis(diphenyl phosphino)-1,1′-binaphthyl (1 mg), tris(dibenzylideneacetone)-dipalladium(0) (0.6 mg) and sodium t-butyloxide (26 mg, 0.27 mmol). The reaction mixture was heated at 80° C. for 12 h under argon. The reaction mixture became deep brown upon heating. The mixture was cooled to RT, diluted with ethyl acetate (10 mL), washed by brine and the organic layer was dried over Na2SO4, and the solvent was evaporated in vacuo. The crude mixture was purified by preparative thin layer plate to afford the title compound (6 mg, yield 10%). 1H-NMR (MeOH-4), 8.51 (d, 2H), 7.61(d, 2H) 7.52(dd, 2H), 7.15-7.25(m, 4H), 5.49(s, 2H); MS ES 313 (M+H)+, 315 (M+3H)+, 316 (M+4H)+, calc. 312; TLC (5:95 v/v methanol-methylene chloride) Rf=0.2.

Workup

temperatureupon heating
temperatureThe mixture was cooled to RT
washwashed by brine
dry with materialthe organic layer was dried over Na2SO4
customthe solvent was evaporated in vacuo
customThe crude mixture was purified by preparative thin layer plate

Sources & evidence

ORD record: ord-ce55ff32496e413aa622f1323061cad3
Source dataset: uspto-grants-2005_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06903101B1

Reaction notes

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