Ammonia → 4-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide

HRID 1755317Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1755317
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:29]=[CH:30][N:31]=3)[N:17]=[C:18]([C:20]3[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][CH:21]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.N.O1CCOCC1.CC[N:41]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>ClCCl.CN(C=O)C>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:29]=[CH:30][N:31]=3)[N:17]=[C:18]([C:20]3[CH:21]=[CH:22][C:23]([C:24]([NH2:41])=[O:26])=[CH:27][CH:28]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Komponenten

9

Edukt 6

HCID 222AmmoniaHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 715256154-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Produkt 1

HCID 715256184-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamideAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (45 mg, 0.11 mmol), 0.5 M ammonia in dioxane solution (23 mg, 1.3 mmol), EDCI (32 mg, 0.163 mmol) and HOBt (22 mg, 0.163 mmol) in dichloromethane (3 mL), DMF (0.5 mL) and Et3N (22 mg, 0.22 mmol) was stirred at room temperature for 16 h. The solution was concentrated in vacuo, washed with water (10 mL×3), and purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=30:1) to give 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide (13 mg, 29%) as a yellow oil. 1H NMR (300 MHz, DMSO): δ 9.68 (s, 1H), 8.82 (s, 1H), 8.44 (s, 1H), 8.23 (s, 1H), 8.12-7.99 (m, 5H), 7.68 (s, 1H), 7.48-7.43 (m, 2H), 6.74 (d, 1H, J=7.8 Hz), 6.09 (d, 1H, J=8.1 Hz), 4.26-4.21 (m, 1H), 3.58-3.40 (m, 2H), 2.09-2.00 (m, 3H), 1.74-1.70 (m, 1H), 1.15 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 414, tR=1.547 min, HPLC: 99.34% at 214 nm, 99.33% at 254 nm, tR=5.357 min.

Aufarbeitung

  1. concentrationThe solution was concentrated in vacuo
  2. washwashed with water (10 mL×3)
  3. custompurified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=30:1)

Quellen und Nachweise

ORD-Eintrag
ord-7e7715cdc00143ec9469187e0f53ab38
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169259B2

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