Acetonitrile → HCID 86696338, compound

HRID 870643Notes

Reaction equation

HRID 870643 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.[F:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:22]=1[CH:23]=[O:24].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:19]3[CH:20]=[CH:21][C:22]([CH:23]=[O:24])=[C:17]([F:16])[CH:18]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 27786543-Fluoro-4-formylphenylboronic acidHCID 86696322HCID 86696322, compound

Product 1

HCID 86696338HCID 86696338, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 178418903HCID 178418903, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (300 mg, 1.1 mmol), 3-fluoro-4-formylphenylboronic acid (230 mg, 1.3 mmol), dichloro-bis(triphenylphosphino) palladium (II) (40 mg, 0.055 mmol), potassium carbonate (230 mg, 1.7 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 4-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzaldehyde (240 mg, 68%) as a yellow solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.39 (s, 1H), 8.28 (dd, J=12.9, 1.5 Hz, 1H), 7.91-8.01 (m, 3H), 7.73 (d, J=9.6 Hz, 1H), 6.54 (d, J=9.6 Hz, 1H), 3.48 (td, J=7.2, 5.8 Hz, 2H), 1.69-1.80 (m, 2H), 1.46-1.57 (m, 2H), 1.03 (t, J=7.5 Hz, 3H); LCMS (ESI) m/e 313.2 [(M+H)+, calcd for C17H18FN4O 313.1].

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-2111bfd0daae430980c5c3102c9e6b27
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

Loading…