Triphenylphosphine → 1-(2,6-Dichlorophenyl)-5-(2,4-difluorophenyl)-3,4-dihydro-7-[2-(1-piperidinyl)ethoxy]-2(1H)-quinolinone

HRID 394059Notes

Reaction equation

HRID 394059 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:18]2[C:13](=[C:14]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[F:27])[CH:15]=[C:16]([OH:19])[CH:17]=2)[CH2:12][CH2:11][C:10]1=[O:28].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[N:48]1([CH2:54][CH2:55]O)[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:18]2[C:13](=[C:14]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[F:27])[CH:15]=[C:16]([O:19][CH2:55][CH2:54][N:48]3[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]3)[CH:17]=2)[CH2:12][CH2:11][C:10]1=[O:28]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 18232N-PiperidinoethanolHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 226480931-(2,6-Dichlorophenyl)-5-(2,4-difluorophenyl)-3,4-dihydro-7-hydroxy-2(1H)-quinolinone2×

Product 1

HCID 101868031-(2,6-Dichlorophenyl)-5-(2,4-difluorophenyl)-3,4-dihydro-7-[2-(1-piperidinyl)ethoxy]-2(1H)-quinolinone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 10 mg of 1-(2,6-dichlorophenyl)-5-(2,4-difluorophenyl)-3,4-dihydro-7-hydroxy-2(1H)-quinolinone (INTERMEDIATE 3) dissolved in 2 mL of anhydrous THF was added 87 mg of Ph3P and 43 mg of 1-piperidine ethanol. The resulting mixture was heated to 65° C. for 10 min. Then 72 mg of diisopropyl azodicarboxylate was added dropwise over 2 min and the mixture was stirred for 1 h at 65° C. The resulting reaction mixture was concentrated and purified by preparative thin-layer chromatography, eluting with 100% EtOAc, to yield 1-(2,6-Dichlorophenyl)-5-(2,4-difluorophenyl)-3,4-dihydro-7-[2-(1-piperidinyl)ethoxy]-2(1H)-quinolinone. Mass spectrum (ESI) 531.3 (M+1). 1H NMR (500 MHz, CDCl3): δ 1H NMR (500 MHz, CDCl3) δ 7.51 (d, J=8 Hz, 2H); 7.38 (t, J=8 Hz, 1H); 7.31 (q, J=6.5 Hz, 1H); 6.98 (m, 2H); 6.54 (s, 1H); 5.90 (s, 1H); 4.08 (s, 2H); 2.83 (m, 6H); 2.61 (s, 4H); 1.68 (s, 4H); 1.48 (s, 2H).

Workup

  1. customThe resulting reaction mixture
  2. concentrationwas concentrated
  3. custompurified by preparative thin-layer chromatography
  4. washeluting with 100% EtOAc

Sources & evidence

ORD record
ord-377d94ee63064109889103b1f52b9df3
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

Loading…