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

HRID 1755317노트

반응식

HRID 1755317 반응식
[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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7e7715cdc00143ec9469187e0f53ab38
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169259B2

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