Triethylamine → 3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide

HRID 1755305Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1755305
[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]=[C:22]([CH:26]=[CH:27][CH:28]=3)[C:23]([OH:25])=O)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.[Cl-].[NH4+].CC[N:36]=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]=[C:22]([CH:26]=[CH:27][CH:28]=3)[C:23]([NH2:36])=[O:25])[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 715255203-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Produkt 1

HCID 715255243-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamideAusbeute 48,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (50 mg, 0.12 mmol), ammonium chloride (25 mg, 1.44 mmol), EDCI (36 mg, 0.18 mmol), HOBT (24 mg, 0.18 mmol) in dichloromethane (3 mL), DMF (0.5 mL) and Et3N (27 mg, 0.24 mmol) was stirred at room temperature for 16 h. The solution was concentrated in vacuo, washed with water (10 mL×3), purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1) to give 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide (24 mg, 48%) as a yellow oil. 1H NMR (300 MHz, DMSO): δ 9.67 (s, 1H), 8.85 (s, 1H), 8.45 (s, 1H), 8.23 (s, 1H), 8.13-7.99 (m, 3H), 7.68-7.59 (m, 2H), 7.49-7.42 (m, 2H), 6.73 (d, 1H, J=7.8 Hz), 6.08 (d, 1H, J=8.1 Hz), 4.25-4.21 (m, 1H), 3.60-3.57 (m, 1H), 3.44-3.38 (m, 1H), 2.06-1.95 (m, 3H), 1.67 (s, 1H), 1.08 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 414, tR=1.633 min, HPLC: 98.33% at 214 nm, 97.74% at 254 nm, tR=5.64 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=20:1)

Quellen und Nachweise

ORD-Eintrag
ord-b22924884ee840f39983eee6ff098173
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169259B2

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