Diisopropylethylamine → 6-Chloro-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943439

반응식

HRID 1943439 반응식
[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]([CH2:7][NH:8][CH:9]2[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[Cl:14][C:15]1[CH:16]=[C:17](Cl)[C:18]2[N:19]([C:21]([C:24]([NH:26][C:27]3[CH:32]=[CH:31][N:30]=[C:29]([F:33])[CH:28]=3)=[O:25])=[CH:22][N:23]=2)[N:20]=1.BrC1C2N(C(C(NC3C=CN=C(F)C=3)=O)=CN=2)N=C(Cl)C=1.BrC1C2N(C(C(NC3C=CN=C(F)C=3)=O)=CN=2)N=C(Cl)C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:14][C:15]1[CH:16]=[C:17]([N:8]([CH:9]2[CH2:11][CH2:10]2)[CH2:7][C:6]2[CH:12]=[CH:13][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:18]2[N:19]([C:21]([C:24]([NH:26][C:27]3[CH:32]=[CH:31][N:30]=[C:29]([F:33])[CH:28]=3)=[O:25])=[CH:22][N:23]=2)[N:20]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 4721289N-((4-methoxyphenyl)methyl)cyclopropanamineHCID 596246836,8-dichloro-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideHCID 866492688-bromo-6-chloro-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 8-bromo-6-chloro-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

생성물 1

HCID 596243286-Chloro-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide수율 78%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

N-(4-methoxybenzyl)cyclopropanamine (381 mg, 2.148 mmol) was added to ˜1:1 mixture of 6,8-dichloro-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 8-bromo-6-chloro-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (467 mg, 1.432 mmol, example 13A) and DIEA (0.500 mL, 2.86 mmol) in DMF (10 mL). The reaction mixture was heated at 80° C. for 1.5 hrs. Water (20 mL) was added, and the solid was collected via Buchner filtration and dried under reduced pressure overnight to afford 6-Chloro-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide as a yellow solid (519 mg, 78%). The crude material was taken into the next step without further purification. LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA). Rt=2.22 minutes. [M+H]=467.21.

후처리

  1. filtrationthe solid was collected via Buchner filtration
  2. customdried under reduced pressure overnight

출처 및 근거

ORD 기록
ord-cb1556c630d2410d9affd1831c360355
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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