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

HRID 1943504노트

반응식

HRID 1943504 반응식
Cl[C:2]1[CH:3]=[C:4]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([Cl:20])[CH:15]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[S:34]1[CH2:39][CH2:38][CH:37]([NH2:40])[CH2:36][CH2:35]1.CN1C(=O)CCC1>CO>[Cl:20][C:16]1[CH:15]=[C:14]([NH:13][C:11]([C:8]2[N:6]3[N:7]=[C:2]([NH:40][CH:37]4[CH2:38][CH2:39][S:34][CH2:35][CH2:36]4)[CH:3]=[C:4]([N:21]([CH:31]4[CH2:32][CH2:33]4)[CH2:22][C:23]4[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=4)[C:5]3=[N:10][CH:9]=2)=[O:12])[CH:19]=[CH:18][N:17]=1

참가 물질

5

반응물 3

HCID 13387N-methyl-2-pyrrolidoneHCID 418807Tetrahydrothiopyran-4-ylamineHCID 596248746-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide

생성물 1

HCID 59624712N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-thiopyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide수율 23.1%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A microwave tube was charged with 6-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide (100 mg, 0.207 mmol), tetrahydro-2H-thiopyran-4-amine (121 mg, 1.034 mmol), and NMP (2 mL). The reaction mixture was irradiated at 120° C. (300 W) for 20 minutes. 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, 60 min gradient, monitored at 254 nm). The product (retention time=68.837 minutes) was isolated and lyophilized to dryness to afford N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-thiopyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (27 mg, 17.32%). HPLC Rt=4.816 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+]=563.9.

후처리

  1. customThe reaction mixture was irradiated at 120° C. (300 W) for 20 minutes
  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, 60 min gradient, monitored at 254 nm)
  4. customThe product (retention time=68.837 minutes) was isolated

출처 및 근거

ORD 기록
ord-551e472aeb924c07a87d95dfde6befda
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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