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 418535Notes

Reaction equation

HRID 418535 reaction equation
[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]

Participants

6

Reactant 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

Product 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)acetamideYield 104%

Conditions

Temperature
0 °C

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-69c8f2f898634fe1af2cfa7cd2a7fa0e
Source dataset
uspto-grants-2012_01
Patent number
US08093265B2

Reaction notes

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