Sodium Bicarbonate → (5R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one

HRID 403254Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 403254
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:6](=O)[CH2:7][CH2:8][C:9]=2[CH:10]=1.[NH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:30])=[C:17]([C@:19]2([CH3:29])[C:25]([F:27])([F:26])[CH2:24][O:23][CH2:22][C:21](=[O:28])[NH:20]2)[CH:18]=1.[B][B][B][B][B][B][B][B][B][B].C([O-])(O)=O.[Na+]>CO.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[CH2:8][CH2:7][CH:6]([NH:12][C:13]3[CH:14]=[CH:15][C:16]([F:30])=[C:17]([C@:19]4([CH3:29])[C:25]([F:26])([F:27])[CH2:24][O:23][CH2:22][C:21](=[O:28])[NH:20]4)[CH:18]=3)[C:5]2=[N:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 516892Sodium BicarbonateHCID 58082858HCID 58082858, VerbindungHCID 68226741(R)-5-(5-amino-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-oneHCID 178419135HCID 178419135, Verbindung

Produkt 1

HCID 68226747(5R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-oneAusbeute 87,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

To a solution of 3-chloro-5,6-dihydro-[1]pyrindin-7-one (28 mg, 167 μmol) in methanol (6 ml) and dichloromethane (750 μl) at 23° C. was added (R)-5-(5-amino-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one (intermediate A21A) (49.9 mg, 182 μmol) followed by decaborane (5.6 mg, 167 μmol) and the mixture was stirred at 23° C. for 22 hours. After completion, the mixture was poured into aqueous NaHCO3 solution, extracted with ethyl acetate, the organic layers were dried over Na2SO4 and the solvent evaporated. The crude material was purified by silica gel flash chromatography with n-heptane/ethyl acetate to give the (5R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one (62 mg, 87%) as an orange solid. MS (ISP): m/z=426.1 [(M+H)+] and 428.1 [(M+2+H)+].

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. dry with materialthe organic layers were dried over Na2SO4
  3. customthe solvent evaporated
  4. customThe crude material was purified by silica gel flash chromatography with n-heptane/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-054a38bd023a4888abeb8569f8f71e37
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08748418B2

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