Acetonitrile → butyl-[3-(1H-indazol-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine

HRID 870652Notes

Reaction equation

HRID 870652 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[NH:16]1[C:24]2[C:19](=[CH:20][C:21](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:23]=2)[CH:18]=[N:17]1.C(=O)([O-])[O-].[K+].[K+].C(#N)C>Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:21]3[CH:20]=[C:19]4[C:24](=[CH:23][CH:22]=3)[NH:16][N:17]=[CH:18]4)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 177504691H-Indazole-5-boronic acid pinacol esterHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

Product 1

HCID 89802283butyl-[3-(1H-indazol-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-amineYield 65.3%

Reagents, catalysts & solvents 2

HCID 178418903HCID 178418903, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (140 mg, 0.50 mmol), (1H-indazole-5-boronic acid pinacol ester (150 mg, 0.60 mmol), dichloro-bis(triphenylphosphino) palladium (II) (20 mg, 0.025 mmol), potassium carbonate (110 mg, 0.75 mmol), acetonitrile (1.5 mL) and H2O (0.5 mL) was heated in a sealed conical vessel at 160° C. for 1000 s by microwave irradiation. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 mL). The combined organic layers were concentrated under reduced pressure to afford an oil that was purified by reverse phase HPLC to afford butyl-[3-(1H-indazol-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine (100 mg, 65%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.62-8.68 (m, 1H), 8.13-8.20 (m, 2H), 8.02 (dd, J=8.8, 1.5 Hz, 1H), 7.94 (d, J=9.9 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.21 (d, J=9.9 Hz, 1H), 3.43 (t, J=7.2 Hz, 2H), 1.66-1.79 (m, 2H), 1.49 (dq, J=15.1, 7.4 Hz, 2H), 0.99 (t, J=7.5 Hz, 3H); LCMS (ESI) m/e 307.2 [(M+H)+, calcd for C17H19N6 307.2].

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2 mL)
  3. concentrationThe combined organic layers were concentrated under reduced pressure
  4. customto afford an oil that
  5. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-f0bf6cc2a6c14a97ae79e3839d8a83dc
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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