Water → HCID 46866575, compound

HRID 2282111Notes

Reaction equation

HRID 2282111 reaction equation
[C:1]([C:3]1[C:4]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[Cl:27])=[C:5]([C:15]([O:17]CC)=O)[S:6][C:7]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([F:14])[CH:9]=1)#[N:2].[OH-].[Na+].O.Cl.C[N:33](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[OH-].[NH4+]>C(#N)C.C(Cl)Cl>[C:1]([C:3]1[C:4]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[Cl:27])=[C:5]([C:15]([NH2:33])=[O:17])[S:6][C:7]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([F:14])[CH:9]=1)#[N:2]

Participants

9

Reactant 6

HCID 962WaterHCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 58095188HCID 58095188, compound

Product 1

HCID 46866575HCID 46866575, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Ethyl 4-cyano-3-(2,4-dichlorophenyl)-5-(2-fluoropyridin-4-yl)thiophene-2-carboxylate (2.33 g, 0.00553 mol) was dissolved in acetonitrile (100 mL) and 1M sodium hydroxide in water (42 mL, 0.0420 mol) was added. The mixture was stirred overnight at room temperature. The mixture was concentrated and the residue was acidified with 1N HCl. The solid was collected, dried, and used in the next step without purification. The above solid was dissolved in methylene chloride (248 mL) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.29 g, 0.0120 mol) and 1-hydroxybenzotriazole hydrate (1.694 g, 0.01106 mol) were added. The mixture was stirred at room temperature for 15 minutes and 33% ammonium hydroxide (20.0 mL, 0.231 mol) was added. The stirring was continued for 2 hours. The mixture was diluted with DCM and washed with water and brine. The organic layer was dried and purified by column chromatography on silica gel (80 g), elution hexane to 60% EtOAc in hexane over 30 minutes. The product was obtained as white solid (1.18 g, 55%). LCMS: (FA) ES+, 392, 394. 1H NMR (400 MHz, d6-DMSO) 8.50 (d, J=5.27 Hz, 1H), 7.85 (d, J=1.79 Hz, 1H), 7.79 (td, J=5.21, 1.52, 1.52 Hz, 1H), 7.65 (s, 1H), 7.63-7.55 (m, 2H), 7.42 (bs, 1H),

Workup

  1. concentrationThe mixture was concentrated
  2. customThe solid was collected
  3. customdried
  4. customused in the next step without purification
  5. dissolutionThe above solid was dissolved in methylene chloride (248 mL)
  6. stirringThe mixture was stirred at room temperature for 15 minutes
  7. waitThe stirring was continued for 2 hours
  8. washwashed with water and brine
  9. customThe organic layer was dried
  10. custompurified by column chromatography on silica gel (80 g), elution hexane to 60% EtOAc in hexane over 30 minutes

Sources & evidence

ORD record
ord-0f764cdfc2fb4c84a4ac2f17bd038688
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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