Nitrogen → HCID 178511600, compound

HRID 1483830Notes

Reaction equation

HRID 1483830 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=3)=[CH:9][N:10]=2)[N:7]=1.[C@H:18]1([NH2:25])[CH2:23][CH2:22][C@H:21]([NH2:24])[CH2:20][CH2:19]1.C(O[Na])(C)(C)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.N#N>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CC(=O)OCC>[Cl:17][C:13]1[CH:12]=[C:11]([C:8]2[N:6]3[N:7]=[C:2]([NH:24][C@H:21]4[CH2:22][CH2:23][C@H:18]([NH2:25])[CH2:19][CH2:20]4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[CH:16]=[CH:15][CH:14]=1

Participants

10

Reactant 5

HCID 947NitrogenHCID 634876Binap, (A+-)-HCID 574186866-Chloro-3-(3-chlorophenyl)imidazo[1,2-b]pyridazineHCID 178418730sodium 2-methylpropan-2-olateHCID 178511674HCID 178511674, compound

Product 1

HCID 178511600HCID 178511600, compoundYield 37.1%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 6-chloro-3-(3-chlorophenyl)imidazo[1,2-b]pyridazine (500 mg, 1.89 mmol) in toluene (10 mL) was added trans-cyclohexane-1,4-diamine (215.9 mg, 1.89 mmol), t-BuONa (302.4 mg, 3.78 mmol), BINAP (117.7 mg, 0.189 mmol), Pd2(dba)3 (173 mg, 0.189 mmol). The mixture was filled with N2 and heated at 110° C. for 4 h. TLC (PE:EA=1:1) showed the reaction was complete. The reaction was poured into water (150 mL), extracted with EA (3×50 mL). The organic layer was dried and condensed. The residue was purified by combi flash (CH2Cl2:MeOH=0˜10:1) to give trans-N1-(3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl)cyclohexane-1,4-diamine (240 mg, yield: 37%) as a yellow solid.

Workup

  1. extractionextracted with EA (3×50 mL)
  2. customThe organic layer was dried
  3. customcondensed
  4. customThe residue was purified by combi flash (CH2Cl2:MeOH=0˜10:1)

Sources & evidence

ORD record
ord-916c503e66ab4d25baf4201a100cc90d
Source dataset
uspto-grants-2016_08
Patent number
US09416132B2

Reaction notes

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