Diisopropylethylamine → N-(4-fluoro-3-methoxybenzyl)-1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxamide

HRID 572691노트

반응식

HRID 572691 반응식
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2[CH2:13][CH:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[O:11][N:10]=2)=[CH:5][C:4]([C:20]([OH:22])=O)=[N:3]1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH2:31])=[CH:26][C:25]=1[O:32][CH3:33].C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH:31][C:20]([C:4]2[CH:5]=[C:6]([C:9]3[CH2:13][CH:12]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[O:11][N:10]=3)[C:7](=[O:8])[N:2]([CH3:1])[N:3]=2)=[O:22])=[CH:26][C:25]=1[O:32][CH3:33]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 442031244-Fluoro-3-methoxybenzylamineHCID 866759381-Methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxylic acid

생성물 1

HCID 86675940N-(4-fluoro-3-methoxybenzyl)-1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxamide수율 41.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxylic acid (150 mg, 0.501 mmol, Preparation #34) in DMF (4 mL) was added (4-fluoro-3-methoxyphenyl)methanamine (93 mg, 0.601 mmol, WO 2008/083056), N-ethyl-N-isopropylpropan-2-amine (194 mg, 1.504 mmol, Spectrochem) and followed by HATU (286 mg, 0.752 mmol, Molekule). The reaction mixture was stirred at RT for 16 h. and was quenched with ice cold water (10 mL). The product was extracted with EtOAc (3×20 mL). The combined organic layers were dried over sodium sulphate and evaporated to dryness under vacuum. The residue obtained was purified by silica gel column chromatography by eluenting with 40-60% EtOAc in hexane. The relevant fractions containing the product were combined and evaporated under reduced pressure to afford N-(4-fluoro-3-methoxybenzyl)-1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxamide 90 mg, (41.1%) as pale yellow solids. 1H NMR (400 MHz, DMSO) δ 9.159-9.127 (m, 1H), 8.143 (s, 1H), 7.422-7.331 (m, 5H), 7.167-7.117 (m, 2H), 6.886-6.849 (m, 1H), 5.812-5.763 (m, 1H), 4.436-4.420 (d, J=6.4 Hz, 2H), 3.964-3.892 (m, 1H) 3.819 (s, 3H), 3.781 (s, 3H), 3.508-3.443 (m, 1H). MS m/z 437.3 (M+H)+;

후처리

  1. customwas quenched with ice cold water (10 mL)
  2. extractionThe product was extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulphate
  4. customevaporated to dryness under vacuum
  5. customThe residue obtained
  6. customwas purified by silica gel column chromatography
  7. additionThe relevant fractions containing the product
  8. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-b86517e4667d4eb3905f3a3d421c88ef
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029409B2

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