4-Aminotetrahydropyran → N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943506노트

반응식

HRID 1943506 반응식
[O:1]1[CH2:6][CH2:5][CH:4]([NH2:7])[CH2:3][CH2:2]1.Cl[C:9]1[CH:10]=[C:11]([N:28]([CH:38]2[CH2:40][CH2:39]2)[CH2:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)[C:12]2[N:13]([C:15]([C:18]([NH:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([Cl:27])[CH:22]=3)=[O:19])=[CH:16][N:17]=2)[N:14]=1>CN1C(=O)CCC1.CO>[Cl:27][C:23]1[CH:22]=[C:21]([NH:20][C:18]([C:15]2[N:13]3[N:14]=[C:9]([NH:7][CH:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[CH:10]=[C:11]([N:28]([CH:38]4[CH2:39][CH2:40]4)[CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[C:12]3=[N:17][CH:16]=2)=[O:19])[CH:26]=[CH:25][N:24]=1

참가 물질

5

반응물 2

HCID 4192234-AminotetrahydropyranHCID 596248746-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide

생성물 1

HCID 59624640N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide수율 12.4%

시약·촉매·용매 2

HCID 887Methanol용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of tetrahydro-2H-pyran-4-amine (105 mg, 1.034 mmol) and 6-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide (50 mg, 0.103 mmol) in NMP (1 mL) was heated to 140° C. The reaction was stirred for 16 hours until starting material was consumed and then cooled to room temperature. The crude reaction product was dissolved in a small amount of MeOH and purified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 40 min gradient, monitored at 220 nm). The product (retention time=47.580 minutes) was isolated and lyophilized to dryness. to afford N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (7 mg, 11.57%). HPLC Rt=4.595 min (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). [M+H+]=548.0.

후처리

  1. customwas consumed
  2. customThe crude reaction product
  3. custompurified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 40 min gradient, monitored at 220 nm)
  4. customThe product (retention time=47.580 minutes) was isolated

출처 및 근거

ORD 기록
ord-19b16da358ab41a384bacd829f12fa05
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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