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

HRID 572691Notes

Reaction equation

HRID 572691 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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)+;

Workup

  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

Sources & evidence

ORD record
ord-b86517e4667d4eb3905f3a3d421c88ef
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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