Hydrochloric Acid → N9-(3,5-dichloro-4-pyridyl)-6-difluoromethoxy-3-ethyl-4-oxo-3,4-dihydro benzo[4,5]furo[2,3-d]pyridazine-9-carboxamide

HRID 1091875Notes

Reaction equation

HRID 1091875 reaction equation
[F:1][CH:2]([F:32])[O:3][C:4]1[C:9]2[O:10][C:11]3[C:12](=[O:19])[N:13]([CH2:17][CH3:18])[N:14]=[CH:15][C:16]=3[C:8]=2[C:7]([C:20]([O:22]C2C=CC([N+]([O-])=O)=CC=2)=O)=[CH:6][CH:5]=1.[NH2:33][C:34]1[C:39]([Cl:40])=[CH:38][N:37]=[CH:36][C:35]=1[Cl:41].[H-].[Na+].Cl>CN(C)C=O.O>[Cl:41][C:35]1[CH:36]=[N:37][CH:38]=[C:39]([Cl:40])[C:34]=1[NH:33][C:20]([C:7]1[C:8]2[C:16]3[CH:15]=[N:14][N:13]([CH2:17][CH3:18])[C:12](=[O:19])[C:11]=3[O:10][C:9]=2[C:4]([O:3][CH:2]([F:32])[F:1])=[CH:5][CH:6]=1)=[O:22]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 898884-Amino-3,5-dichloropyridineHCID 66592549HCID 66592549, compound

Product 1

HCID 11684203N9-(3,5-dichloro-4-pyridyl)-6-difluoromethoxy-3-ethyl-4-oxo-3,4-dihydro benzo[4,5]furo[2,3-d]pyridazine-9-carboxamideYield 210.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

A suspension of 4-nitrophenyl 6-difluoromethoxy-3-ethyl-4-oxo-3,4-dihydrobenzo[4,5]furo[2,3-d]pyridazine-9-carboxylate (from step III) (81 mg, 0.18 mmol) and 4-amino-3,5-dichloro pyridine (32 mg, 0.19 mmol) in dimethyl formamide (3 ml) was cooled to −30-40° C. under nitrogen. Then sodium hydride (15 mg, 0.36 mmol) was added lotwise at the same temp. under nitrogen. Progress of reaction was monitored by TLC. At the end, reaction mixture was cooled to 0-10° C. Water (100 ml) was added dropwise to the reaction mixture at 0-10° C. and acidified with dilute HCl. the precipitate obtained was filtered and dried in oven. The solid was purified by column chromatography using 20% acetone in chloroform. 178 mg pure product was obtained as off white solid.

Workup

  1. customProgress of reaction
  2. customAt the end, reaction mixture
  3. temperaturewas cooled to 0-10° C
  4. customthe precipitate obtained
  5. filtrationwas filtered
  6. customdried in oven
  7. customThe solid was purified by column chromatography

Sources & evidence

ORD record
ord-503df9d254ef474e8cffe218ab159ba5
Source dataset
uspto-grants-2012_03
Patent number
US08129401B2

Reaction notes

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