Hydrochloric Acid → N-(3-(2-(2-chloropyriMidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

HRID 239250Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 239250
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[S:9]([NH:12][C:13]1[C:14]([F:23])=[C:15]([CH:20]=[CH:21][CH:22]=1)[C:16](OC)=[O:17])(=[O:11])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:34][C:35]1[N:40]=[C:39]([CH3:41])[CH:38]=[CH:37][N:36]=1.Cl>C1COCC1.CCOC(C)=O>[Cl:34][C:35]1[N:40]=[C:39]([CH2:41][C:16]([C:15]2[C:14]([F:23])=[C:13]([NH:12][S:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])(=[O:10])=[O:11])[CH:22]=[CH:21][CH:20]=2)=[O:17])[CH:38]=[CH:37][N:36]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 116296072-Chloro-4-methylpyrimidineHCID 57989692Benzoic acid, 3-[[(2,6-difluorophenyl)sulfonyl]amino]-2-fluoro-, methyl ester

Produkt 1

HCID 57989720N-(3-(2-(2-chloropyriMidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamideAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel3×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

In a 1000 mL flask was placed methyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorobenzoate (9.64 g, 27.9 mmol) and THF (200 mL) was added. The flask was placed in an ice/water bath and LiHMDS (90 mL, 90 mmol) was added. 2-Chloro-4-methylpyrimidine (4.5 g, 35.0 mmol) in THF (60 mL) was added dropwise via addition funnel. After the addition was complete, the reaction was allowed to warm to 20° C. over 1 h. The THF volume was reduced to half under reduced pressure and then treated with 6 N HCl. EtOAc was added and the layers were separated. The aqueous layer was extracted twice with EtOAc and the combined organic layer was washed once with brine, dried over NaSO4, and concentrated. The residue was triturated with EtOAc/ether to afford 8.71 g (71%) of the title compound of Step D. MS (ESI): 442 [M+H]+.

Aufarbeitung

  1. customIn a 1000 mL flask was placed
  2. customThe flask was placed in an ice/water bath
  3. additionAfter the addition
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted twice with EtOAc
  6. washthe combined organic layer was washed once with brine
  7. dry with materialdried over NaSO4
  8. concentrationconcentrated
  9. customThe residue was triturated with EtOAc/ether

Quellen und Nachweise

ORD-Eintrag
ord-64708cb393e045f89ffce6d4f3101f0e
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642759B2

Notizen zur Reaktion

Wird geladen…