Sodium t-butoxide → HCID 178490933, compound

HRID 2239893Notes

Reaction equation

HRID 2239893 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N:19]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]2[N:6]([C:8]([CH:11]=[CH:12][C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[CH:9][N:10]=2)[N:7]=1.C(N1CCCC(NC2C=C(N(CC3C=CC(OC)=CC=3)C3C=CC=CC=3)C3N(C(C#N)=CN=3)N=2)C1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].[C@H:82]1([NH2:89])[CH2:87][CH2:86][C@H:85]([NH2:88])[CH2:84][CH2:83]1>CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd].C1(C)C=CC=CC=1>[NH2:88][C@H:85]1[CH2:86][CH2:87][C@H:82]([NH:89][C:2]2[CH:3]=[C:4]([N:19]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:5]3[N:6]([C:8]([CH:11]=[CH:12][C:13]4[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=4)=[CH:9][N:10]=3)[N:7]=2)[CH2:83][CH2:84]1

Participants

7

Reactant 4

HCID 23676156Sodium t-butoxideHCID 68481210HCID 68481210, compoundHCID 86618523HCID 86618523, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178490933HCID 178490933, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 119822622-(2'-Di-tert-butylphosphine)biphenylpalladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

6-chloro-N-(4-methoxybenzyl)-N-phenyl-3-(2-(pyridin-4-yl)vinyl)imidazo[1,2-b]pyridazin-8-amine (75 mg, 0.16 mmol) from (1b), sodium tert-butoxide (22 mg, 0.22 mmol), trans-1,4-cyclohexanediamine (22 mg, 0.19 mmol) and acetato(2′-di-tert-butylphosphino-1,1′-biphenyl-2-yl)palladium (II) (7.4 mg, 0.01 mmole) were purged with argon for 15 min. then toluene (0.6 mL) was added via syringe. The contents were sonicated briefly and heated at 85° C. for 2 h. After cooling to room temperature, the mixture was partitioned between EtOAc (200 mL) and water (20 mL), and the organic layer was washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by reverse phase preparative HPLC to provide N6-(trans-4-aminocyclohexyl)-N8-(4-methoxybenzyl)-N8-phenyl-3-(2-(pyridin-4-yl)vinyl)imidazo[1,2-b]pyridazine-6,8-diamine as a yellow solid (32 mg, 38%). LCMS[M+H]+ 546.

Workup

  1. customThe contents were sonicated briefly
  2. temperatureAfter cooling to room temperature
  3. customthe mixture was partitioned between EtOAc (200 mL) and water (20 mL)
  4. washthe organic layer was washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-24ae76a0eb804313bd1c0c0db8c8e96f
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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