Toluene → (R)-N-(2-(1-azidopropan-2-yl)-6-methyl-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamide

HRID 418535Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 418535
[F:1][C:2]1[CH:3]=[C:4]([CH2:12][C:13]([NH:15][C:16]2[C:25]([CH3:26])=[CH:24][CH:23]=[C:22]3[C:17]=2[CH:18]=[CH:19][N:20]([C@H:28]([CH3:31])[CH2:29]O)[C:21]3=[O:27])=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].C(Cl)Cl.C1(C)C=CC=CC=1.C1C=CC(OP(OC2C=CC=CC=2)([N:51]=[N+:52]=[N-:53])=O)=CC=1.N12CCCN=C1CCCCC2>>[N:51]([CH2:29][C@H:28]([N:20]1[CH:19]=[CH:18][C:17]2[C:22](=[CH:23][CH:24]=[C:25]([CH3:26])[C:16]=2[NH:15][C:13](=[O:14])[CH2:12][C:4]2[CH:5]=[CH:6][C:7]([C:8]([F:11])([F:9])[F:10])=[C:2]([F:1])[CH:3]=2)[C:21]1=[O:27])[CH3:31])=[N+:52]=[N-:53]

Komponenten

6

Edukt 5

HCID 1140TolueneHCID 6344DichloromethaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 123414Diphenylphosphoryl azideHCID 25013922(R)-2-(3-fluoro-4-(trifluoromethyl)phenyl)-N-(2-(1-hydroxypropan-2-yl)-6-methyl-1-oxo-1,2-dihydroisoquinolin-5-yl)acetamide

Produkt 1

HCID 59845723(R)-N-(2-(1-azidopropan-2-yl)-6-methyl-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamideAusbeute 104 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of (R)-2-(3-fluoro-4-(trifluoromethyl)phenyl)-N-(2-(1-hydroxypropan-2-yl)-6-methyl-1-oxo-1,2-dihydroisoquinolin-5-yl)acetamide (0.5 g, 0.001 mol) in methylene chloride (20 mL, 0.3 mol) and toluene (10 mL, 0.09 mol) was cooled to 0° C. and treated with diphenylphosphonic azide (600 mg, 0.002 mol), followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.3 g, 0.002 mol) under nitrogen. The mixture was stirred at 0° C. for 2 h then allowed to warm to room temperature and was stirred overnight. The mixture was concentrated and the residue was treated with water (50 mL) and ethyl acetate (100 mL). The organic layer was separated, washed with brine, dried and evaporated. The residue was purified via flash chromatography to afford the desired product as a clear oil (0.48 g, yield 90%).

Aufarbeitung

  1. temperatureto warm to room temperature
  2. stirringwas stirred overnight
  3. concentrationThe mixture was concentrated
  4. additionthe residue was treated with water (50 mL) and ethyl acetate (100 mL)
  5. customThe organic layer was separated
  6. washwashed with brine
  7. customdried
  8. customevaporated
  9. customThe residue was purified via flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-69c8f2f898634fe1af2cfa7cd2a7fa0e
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093265B2

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