Potassium Phosphate, Tribasic → Tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate

HRID 870657Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 870657
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:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:18]=1[CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24].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>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:30]3[CH:29]=[CH:28][C:18]([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[C:17]([F:16])[CH:31]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 669802924-(n-Boc-aminomethyl)-3-fluorobenzeneboronic acid pinacol esterHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

Produkt 1

HCID 86696354Tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamateAusbeute 38 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
145 °C

Versuchsvorschrift

To a mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (187 mg, 0.7 mmol), tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (293 mg, 1.2 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (24 mg, 0.034 mmol) and tripotassium phosphate (144 mg, 1.04 mmol) was added 3:1 acetonitrile/water (3 mL). The resulting mixture was heated at 145° C. (microwave) for 800 s. The reaction was then filtered and concentrated. The residue was dissolved in methanol, and then filtered again. The filtration was finally purified by preparative HPLC (neutral) to afford tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate (110 mg, 38% yield) as a white solid: 1H NMR (CHLOROFORM-d) δ: 8.02 (dd, J=11.9, 1.3 Hz, 1H), 7.78-7.89 (m, 2H), 7.74 (d, J=9.6 Hz, 1H), 7.43 (t, J=8.0 Hz, 1H), 7.28 (s, 2H), 6.52 (d, J=9.6 Hz, 1H), 4.95 (br. s., 1H), 4.31-4.57 (m, 3H), 3.45 (td, J=7.1, 5.6 Hz, 2H), 1.68-1.80 (m, 2H), 1.02 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 414.3 [(M+H)+, calcd for C22H29FN5O2 414.2].

Aufarbeitung

  1. filtrationThe reaction was then filtered
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in methanol
  4. filtrationfiltered again
  5. filtrationThe filtration
  6. customwas finally purified by preparative HPLC (neutral)

Quellen und Nachweise

ORD-Eintrag
ord-08773336cd8d48a1a9c43f4eb4a3b260
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969565B2

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