Dimethylformamide → Imidazo[1,2-b]pyridazine derivative 7

HRID 2096296

Reaktionsgleichung

Reaktionsgleichung von HRID 2096296
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH2:23])=[CH:21][N:22]=2)[N:19]=1.[CH3:24][S:25]([NH:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=1)(=[O:27])=[O:26].CN(C=O)C.CCN(C(C)C)C(C)C>CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH:23][C:33](=[O:34])[C:32]3[CH:36]=[CH:37][C:29]([NH:28][S:25]([CH3:24])(=[O:27])=[O:26])=[CH:30][CH:31]=3)=[CH:21][N:22]=2)[N:19]=1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2506534-(Methylsulfonamido)benzoic acidHCID 58334496(R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine

Produkt 1

HCID 46182706Imidazo[1,2-b]pyridazine derivative 7Ausbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A reaction vial was charged with (R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine (Preparation B; 30 mg, 0.095 mmol), 4-(methylsulfonamido)benzoic acid (41 mg, 0.19 mmol), and 2(1H-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uranium hexafluorophophate methanaminium (HATU; 72 mg, 0.19 mmol). DMF (0.8 mL) was added to the mixture to make a solution. The reaction mixture was cooled in an ice bath for 10 minutes before DIEA (0.05 mL, 0.29 mmol) was added dropwise. After addition, reaction was warmed to ambient temperature and stirred overnight. The reaction mixture was diluted with EtOAc (20 mL), washed with water and brine (10 mL each), and concentrated. The crude material was purified by reverse-phase column chromatography, eluting with 5 to 60% acetonitrile/water to yield (R)—N-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(methylsulfonamido)benzamide as a yellowish solid (13 mg, 27% yield). MS (apci negative) m/z=511.4 (M−H).

Aufarbeitung

  1. customA reaction
  2. additionwas added dropwise
  3. additionAfter addition, reaction
  4. washwashed with water and brine (10 mL each)
  5. concentrationconcentrated
  6. customThe crude material was purified by reverse-phase column chromatography
  7. washeluting with 5 to 60% acetonitrile/water

Quellen und Nachweise

ORD-Eintrag
ord-2beb17e452d244ab9488dc110c34701b
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08450322B2

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