1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide

HRID 1755337Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1755337
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10].[N:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][NH2:38])=[CH:32][CH:31]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:19]=[CH:20][C:21]([C:22]([NH:38][CH2:37][CH2:36][C:33]4[CH:34]=[CH:35][N:30]=[CH:31][CH:32]=4)=[O:24])=[CH:25][CH:26]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10]

Komponenten

9

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 832754-PyridineethanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 715258044-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Produkt 1

HCID 715258054-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamideAusbeute 72,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (47 mg, 0.12 mmol), 2-(pyridin-4-yl)ethanamine (16 mg, 0.132 mmol), HATU (50 mg, 0.132 mmol), DIPEA (18 mg, 0.144 mmol), DMAP (18 mg, 0.144 mmol) and EDCI (28 mg, 0.144 mmol) in DMF (3 mL) was stirred at room temperature for 16 h. Ethyl acetate (50 mL) was added then the mixture was washed with water (2×2 mL) and brine (2×2 mL), then dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was washed with ether and filtered to afford 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide (43 mg, 72%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.96 (s, 1H), 8.71 (t, 1H, J=5.4 Hz), 8.53-8.46 (m, 3H), 8.21 (s, 1H), 8.03-7.94 (m, 4 h), 7.67 (s, 1H), 7.42 (d, 1H, J=8.4 Hz), 7.29-7.27 (m, 2H), 7.11 (d, 1H, J=8.4 Hz), 4.01 (s, 3H), 3.78 (s, 3H), 3.60-3.54 (m, 2H), 2.90 (t, 2H, J=7.2 Hz). LC-MS: [M+H]+, 496, tR=1.226 min, HPLC: 98.86% at 214 nm, 98.46% at 254 nm, tR=3.144 min.

Aufarbeitung

  1. washthe mixture was washed with water (2×2 mL) and brine (2×2 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. washThe residue was washed with ether
  5. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-772416139bc04472ac7d5530c089a029
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169259B2

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