Ethanol → HCID 66615239, compound

HRID 2239890Notes

Reaction equation

HRID 2239890 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:27][CH:28]3[CH2:33][CH2:32][CH:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:30][CH2:29]3)[CH:9]=[C:10]([N:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.[CH:42]1(B(O)O)[CH2:44][CH2:43]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CCO>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:42]1([C:2]2[N:6]3[N:7]=[C:8]([NH:27][CH:28]4[CH2:33][CH2:32][CH:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:30][CH2:29]4)[CH:9]=[C:10]([N:11]([CH2:18][C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:5]3=[N:4][CH:3]=2)[CH2:44][CH2:43]1

Participants

7

Reactant 4

HCID 702EthanolHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 68483500HCID 68483500, compound

Product 1

HCID 66615239HCID 66615239, compoundYield 15.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

tert-Butyl 4-(3-bromo-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazin-6-ylamino)cyclohexylcarbamate (30 mg, 0.048 mmol) from (1a) and cyclopropylboronic acid (10 mg, 0.090 mmol) in toluene were purged with argon for 15 min, then aq. K3PO4 (2M, 0.06 mL), EtOH (0.04 mL) and tetrakis(triphenylphosphine)palladium(0) were added sequentially. The mixture was heated at 120° C. for 20 h. After cooling to room temperature, the mixture was partitioned between EtOAc (20 mL) and water (5 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 tert-butyl 4-(3-cyclopropyl-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazin-6-ylamino)cyclohexylcarbamate as a cream colored oil (4.3 mg, 15%) LCMS [M+H]+ 583.

Workup

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

Sources & evidence

ORD record
ord-07579d5db31149b4900d4a3f46fb1ad8
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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