1,2-Dibromoethane → (3R)-4-(2-chloro-6-(1-(S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine

HRID 888989

Reaktionsgleichung

Reaktionsgleichung von HRID 888989
[OH-].[Na+].[Cl:3][C:4]1[N:9]=[C:8]([CH2:10][S:11]([CH3:20])(=[O:19])=[N:12]C(=O)C(F)(F)F)[CH:7]=[C:6]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][C@H:22]2[CH3:27])[N:5]=1.Br[CH2:29][CH2:30]Br>[Br-].C([N+](CCCCCCCC)(CCCCCCCC)CCCCCCCC)CCCCCCC.CN1C2C(N=C(N)NC=2NCC1CNC1C=CC(C(NC(C(O)=O)CCC(O)=O)=O)=CC=1)=O>[Cl:3][C:4]1[N:5]=[C:6]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][C@H:22]2[CH3:27])[CH:7]=[C:8]([C:10]2([S:11]([CH3:20])(=[NH:12])=[O:19])[CH2:30][CH2:29]2)[N:9]=1

Komponenten

6

Edukt 3

HCID 78391,2-Dibromoethane2×HCID 14798Sodium HydroxideHCID 86660215N-[({2-chloro-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methyl)(methyl)oxido-lambda6-sulfanylidene]-2,2,2-trifluoroacetamide

Produkt 1

HCID 86660214(3R)-4-(2-chloro-6-(1-(S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholineAusbeute 66,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 2734117Tetraoctylammonium bromideKatalysatorHCID 178479889HCID 178479889, VerbindungLösungsmittel2×

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

Sodium hydroxide (Sigma-Aldrich 415413, d=1.515 g/ml, 217 ml of a 50% solution, 4059.84 mmol) was added to N-[({2-chloro-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl}methyl)(methyl)oxido-λ6-sulfanylidene]-2,2,2-trifluoroacetamide (27.12 g, 67.66 mmol), 1,2-dibromoethane (23.32 ml, 270.66 mmol) and tetraoctylammonium bromide (3.70 g, 6.77 mmol) in methyl THF (1000 ml) at 20° C. under nitrogen. The resulting mixture was stirred at 20° C. for 24 hours. Further 1,2-dibromoethane (23.32 ml, 270.66 mmol) was added and the mixture was stirred at 20° C. for a further 24 hours. The reaction mixture was diluted with methyl THF (1000 ml) and the aqueous layer separated. The organic layer was diluted further with EtOAc (1000 ml) and washed with water (1500 ml). The organic layer was dried over MgSO4, filtered and then evaporated. The residue was purified by flash chromatography on silica, eluting with a gradient of 0 to 5% MeOH in DCM. Pure fractions were evaporated to afford (3R)-4-(2-chloro-6-(1-(S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (14.80 g, 66%); 1H NMR (400 MHz, DMSO-d6) 1.21 (3H, d), 1.39 (3H, m), 1.62-1.71 (1H, m), 3.01 (3H, s), 3.43 (1H, tt), 3.58 (1H, dd), 3.72 (1H, d), 3.82 (1H, d), 3.93 (1H, dd), 4.01 (1H, s), 4.38 (1H, s), 6.96 (1H, d); m/z: (ES+) MH+, 331.46 and 333.

Aufarbeitung

  1. stirringthe mixture was stirred at 20° C. for a further 24 hours
  2. customthe aqueous layer separated
  3. additionThe organic layer was diluted further with EtOAc (1000 ml)
  4. washwashed with water (1500 ml)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash chromatography on silica
  9. washeluting with a gradient of 0 to 5% MeOH in DCM
  10. customPure fractions were evaporated

Quellen und Nachweise

ORD-Eintrag
ord-5857ea5c590742f9b91d51af3eb2b17b
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08252802B2

Verknüpfte Notizen

Wird geladen…