Triethylamine → (E)-N-(4-(difluoromethoxy)phenyl)-6-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)vinyl)pyridazin-3-amine

HRID 77492

Reaction equation

HRID 77492 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[CH:5]2.[F:17][CH:18]([F:35])[O:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]2[N:28]=[N:29][C:30]([CH:33]=[CH2:34])=[CH:31][CH:32]=2)=[CH:22][CH:21]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)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.C(Cl)(Cl)Cl.[Pd].[Pd]>[F:35][CH:18]([F:17])[O:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]2[N:28]=[N:29][C:30](/[CH:33]=[CH:34]/[C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[N:6]=[CH:5]4)=[CH:31][CH:32]=2)=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 667934695-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleHCID 86679785N-(4-(difluoromethoxy)phenyl)-6-vinylpyridazin-3-amine

Product 1

HCID 86679786(E)-N-(4-(difluoromethoxy)phenyl)-6-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)vinyl)pyridazin-3-amine

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.1 g, 0.305 mmol) in ACN (5 mL) were added N-(4-(difluoromethoxy)phenyl)-6-vinylpyridazin-3-amine (0.080 g, 0.305 mmol), tri-o-tolylphosphine (0.037 g, 0.122 mmol), and triethylamine (0.127 mL, 0.914 mmol). The reaction mixture was purged with nitrogen for 5 min. Tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (0.032 g, 0.030 mmol) was added and the reaction mixture was heated at 90° C. for 18 h. The reaction mixture was filtered through a pad of celite and rinsed with ethyl acetate. The organic layer was concentrated and purified by flash chromatography on silica gel using ethyl acetate/hexane to give (E)-N-(4-(difluoromethoxy)phenyl)-6-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)vinyl)pyridazin-3-amine as apale yellow solid (0.13 g, 87%). LCMS (ES-API), m/z 464.6 (M+H).

Workup

  1. customThe reaction mixture was purged with nitrogen for 5 min
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washrinsed with ethyl acetate
  4. concentrationThe organic layer was concentrated
  5. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-dce128ad6b86407a963c937c209974ce
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Linked notes

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