6-Amino-3-chloropyridazine → HCID 57718282, compound

HRID 1366865Notes

Reaction equation

HRID 1366865 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([CH3:9])=[CH:4][C:3]=1[S:10]([NH:13][C:14]1[N:15]=[N:16][C:17](Cl)=[CH:18][CH:19]=1)(=[O:12])=[O:11].NC1N=NC(Cl)=CC=1.ClC1C=C(Cl)C(C)=CC=1S(Cl)(=O)=O.[N:42]1([S:48]([C:51]2[CH:56]=[CH:55][C:54]([SH:57])=[CH:53][CH:52]=2)(=[O:50])=[O:49])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1.CC(C)([O-])C.[K+].O(C1C=CC=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1>CN1CCCC1=O.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(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([CH3:9])=[CH:4][C:3]=1[S:10]([NH:13][C:14]1[N:15]=[N:16][C:17]([S:57][C:54]2[CH:53]=[CH:52][C:51]([S:48]([N:42]3[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]3)(=[O:49])=[O:50])=[CH:56][CH:55]=2)=[CH:18][CH:19]=1)(=[O:12])=[O:11]

Participants

10

Reactant 6

HCID 216436-Amino-3-chloropyridazineHCID 1199142,4-Dichloro-5-methylbenzene-1-sulphonyl chlorideHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 23665647Potassium tert-butoxideHCID 25040283HCID 25040283, compoundHCID 577182904-(N-piperidinylsulfonyl)thiophenol

Product 1

HCID 57718282HCID 57718282, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 3-(2,4-dichloro-5-methylphenylsulfonylamino)-6-chloropyridazine (by reaction of 3-amino-6-chloropyridazine and 2,4-dichloro-5-methylphenylsulfonyl chloride (100 mg, 0.28 mmol) in 1-methyl-2-pyrrolidinone (1 mL) was added 4-(N-piperidinylsulfonyl)thiophenol (80 mg, 0.31 mmol), potassium tert-butoxide (37 mg, 0.33 mmol), tris(dibenzylideneacetone)dipalladium (0) (25 mg, 27 μmol) and (oxydi-2,1-phenylene)bis-(diphenylphosphine) (30 mg, 56 μmol). The mixture was stirred using a vortex stirrer until homogeneous, sealed under nitrogen, and microwaved at 120° C. for 5 minutes using powerMAX™. The reaction mixture was then added to ethyl acetate (50 mL), extracted with sodium bicarbonate (sat., aq., 3×25 mL), dried over magnesium sulphate, and concentrated under reduced pressure to a dark brown oil. Flash chromatography (SiO2, ethyl acetate:cyclohexane 1:2) afforded a pale yellow solid (32 mg, 20%). 1H NMR (CDCl3): 7.98 & 7.39 (2×1 H, 2×s, A-ring CH's), 7.73 & 7.5 (2×2 H, 2×d, 2×J 10 Hz, Ar CH's of C-ring), 7.15 & 7.08 (2×1 H, 2×d, 2×J 12 Hz, B-ring CH's), 2.99-2.92 (4H, m, CH2NCH2), 2.32 (3H, s, CH3), 1.65-1.53 (4 H, m, CH2CH2CH2CH2CH2), 1.43-1.30 (2 H, m, CH2CH2CH2CH2CH2). Hplc (Luna 2, Gradient 5): rt=6.38 minutes. LC/MS rt=7.15 minutes, 573/575 (MH+).

Workup

  1. customsealed under nitrogen
  2. custommicrowaved at 120° C. for 5 minutes
  3. extractionextracted with sodium bicarbonate (sat., aq., 3×25 mL)
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure to a dark brown oil

Sources & evidence

ORD record
ord-7ad3d8285a3c4e94bcc830a55c48e888
Source dataset
uspto-grants-2011_02
Patent number
US07893077B2

Reaction notes

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