Potassium Phosphate, Tribasic → 3-(6-aminopyridin-3-yl)-N-butylimidazo[1,2-b]pyridazin-6-amine

HRID 870649Notes

Reaction equation

HRID 870649 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.C(OC(=O)[NH:22][C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C.O>[NH2:22][C:23]1[N:24]=[CH:25][C:26]([C:2]2[N:6]3[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]3=[N:4][CH:3]=2)=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 17750222tert-butyl N-(5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamateHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

Product 1

HCID 866963453-(6-aminopyridin-3-yl)-N-butylimidazo[1,2-b]pyridazin-6-amineYield 63.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
145 °C

Procedure

To a mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (75 mg, 0.28 mmol), tert-butyl(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamate (107 mg, 0.33 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (10 mg, 0.014 mmol) and potassium phosphate (58 mg, 0.42 mmol) was added 3:1 acetonitrile/water (2 mL). The resulting mixture was heated at 145° C. (microwave) for 1000 s. The reaction was then filtered and concentrated. The residue was finally purified by preparative HPLC (neutral) to afford 3-(6-aminopyridin-3-yl)-N-butylimidazo[1,2-b]pyridazin-6-amine (50.3 mg, 47% yield) as a yellow solid: 1H NMR (METHANOL-d4) δ: 8.72 (d, J=1.8 Hz, 1H), 8.08 (dd, J=8.7, 2.3 Hz, 1H), 7.58 (s, 1H), 7.52 (d, J=9.7 Hz, 1H), 6.58-6.66 (m, 2H), 4.78-4.88 (m, 11H), 3.27-3.33 (m, 3H), 1.62 (d, J=7.1 Hz, 2H), 1.42 (d, J=7.9 Hz, 2H), 0.91-0.97 (m, 3H); LRMS (ESI) m/e 283.4 [(M+H)+, calcd for C15H19N6 283.2].

Workup

  1. filtrationThe reaction was then filtered
  2. concentrationconcentrated
  3. customThe residue was finally purified by preparative HPLC (neutral)

Sources & evidence

ORD record
ord-88db0a200e9a486ab80577d603d78ad0
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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