Tetrahydrofuran → HCID 57978015, compound

HRID 1865827Notes

Reaction equation

HRID 1865827 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([NH:14][NH2:15])=[N:12][N:11]([CH2:16][C:17]3[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[C:10](=[O:28])[C:9]=2[C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)=[CH:4][CH:3]=1.[CH2:35]1C[O:38][CH2:37][CH2:36]1.CCN(CC)CC.C(Cl)(=O)CC>CCOC(C)=O.C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([NH:14][NH:15][C:37](=[O:38])[CH2:36][CH3:35])=[N:12][N:11]([CH2:16][C:17]3[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[C:10](=[O:28])[C:9]=2[C:29]2[CH:30]=[CH:31][N:32]=[CH:33][CH:34]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 57978019HCID 57978019, compound

Product 1

HCID 57978015HCID 57978015, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask was added 5-(4-chlorophenyl)-6-hydrazinyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-4-(pyridin-4-yl)pyridazin-3(2H)-one (200 mg, 0.41 mmol), THF (5 ml), Et3N (124 mg, 1.232 mmol) followed by propionyl chloride (57 mg, 0.616 mmol). The reaction was then stirred at rt for 20 min. The reaction mixture was diluted with EtOAc (30 ml). The resulting solution was wash with water (2×10 ml) and saturated aqueous NaCl (10 ml). The organic layer was then slurried with MgSO4 to remove excess water, filtered and concentrated to give the crude product. The crude product was purified using an automated column chromatography system (ISCO, 12 gm silica gel) eluting with 100% EtOAc for 10 min, then 5% MeOH in CH2Cl2 to give product N′-(4-(4-chlorophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5-(pyridin-4-yl)-1,6-dihydropyridazin-3-yl)propionohydrazide as light yellow solid 140 mg(63% yield). HPLC retention time (method A)1.892 min; LCMS (M+1)=543.3.

Workup

  1. washThe resulting solution was wash with water (2×10 ml) and saturated aqueous NaCl (10 ml)
  2. customto remove excess water
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product
  6. customThe crude product was purified
  7. washeluting with 100% EtOAc for 10 min

Sources & evidence

ORD record
ord-b8fe62c59d4343ea8fae004542812274
Source dataset
uspto-grants-2009_12
Patent number
US07629342B2

Reaction notes

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