Sodium borohydride → N-(cyclopropylmethyl)-3-[8-(2,6-difluorophenyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzamide

HRID 222988

Reaktionsgleichung

Reaktionsgleichung von HRID 222988
[CH:1]1([CH2:4][NH:5][C:6](=[O:35])[C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([C:14]3[C:15]4[CH:25]=[CH:24][C:23](=[O:26])[N:22]([C:27]5[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=5[F:34])[C:16]=4[N:17]=[C:18](SC)[N:19]=3)[CH:8]=2)[CH2:3][CH2:2]1.[BH4-].[Na+]>CO.O.O.O.O.O.O.[Ni](Cl)Cl>[CH:1]1([CH2:4][NH:5][C:6](=[O:35])[C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([C:14]3[C:15]4[CH:25]=[CH:24][C:23](=[O:26])[N:22]([C:27]5[C:28]([F:34])=[CH:29][CH:30]=[CH:31][C:32]=5[F:33])[C:16]=4[N:17]=[CH:18][N:19]=3)[CH:8]=2)[CH2:3][CH2:2]1

Komponenten

5

Edukt 2

HCID 4311764Sodium borohydrideHCID 57434552N-(cyclopropylmethyl)-3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzamide

Produkt 1

HCID 11948233N-(cyclopropylmethyl)-3-[8-(2,6-difluorophenyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzamideAusbeute 8,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11791229Dichloronickel;hexahydrateKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

N-(cyclopropylmethyl)-3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzamide (13.5 mg, 0.027 mmol), was dissolved in anhydrous methanol (2 mL) and was added to a tube containing nickel chloride hexahydrate (2 mg). The tube was placed under an atmosphere of nitrogen and cooled using a dry-ice/acetone bath to about −15° C. Sodium borohydride (2 mg) was then added (nitrogen removed during addition and then replaced) and the solution turned black. The solution was stirred in the dry ice/acetone bath for 1.5 h. 1 N HCl (4 mL) was added and the solution was allowed to warm to room temperature and stirred under an air atmosphere for about 2 hours. Dichloromethane (2 mL) was added to the solution and it was stirred vigorously for 10 min. The solution was filtered through a hydrophobic frit packed with celite and was washed with further dichloromethane (2 mL×2). The filtrate was concentrated and purified by HPLC to give the title product (1 mg, 8.2%). LC-MS m/z 447 (M+H)+, 2.98 min (ret time). 1H-NMR (d6-DMSO) δ 0.22 (m, 2H), 0.42 (m, 2H), 1.01 (br s, 1H), 2.23 (s, 3H), 3.14 (br s, 2H), 6.87 (m, 1H), 7.43 (m, 2H), 7.65 (m, 2H), 7.95 (m, 2H), 8.60 (m, 1H), 9.07 (s, 1H).

Aufarbeitung

  1. additionwas added to a tube
  2. temperaturecooled
  3. customto about −15° C
  4. customremoved during addition
  5. addition1 N HCl (4 mL) was added
  6. stirringstirred under an air atmosphere for about 2 hours
  7. additionDichloromethane (2 mL) was added to the solution and it
  8. stirringwas stirred vigorously for 10 min
  9. filtrationThe solution was filtered through a hydrophobic frit
  10. washwas washed with further dichloromethane (2 mL×2)
  11. concentrationThe filtrate was concentrated
  12. custompurified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-80d2315863594b7a8c05a00978dd54da
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08207176B2

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