Triphenylphosphine → Methyl 6-[4-({[3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

HRID 2423476Notes

Reaction equation

HRID 2423476 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[CH:12]=[CH:11]3)=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([Cl:39])[C:28]=1[C:29]1[C:33]([CH2:34]O)=[C:32]([CH:36]([CH3:38])[CH3:37])[O:31][N:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[Cl:39][C:27]1[CH:26]=[N:25][CH:24]=[C:23]([Cl:22])[C:28]=1[C:29]1[C:33]([CH2:34][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:9]=[C:10]4[C:15](=[CH:16][CH:17]=3)[N:14]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[CH:12]=[CH:11]4)=[CH:4][CH:3]=2)=[C:32]([CH:36]([CH3:37])[CH3:38])[O:31][N:30]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 59321540Methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylateHCID 59709040[3-(3,5-Dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methanol

Product 1

HCID 59321521Methyl 6-[4-({[3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate (100 mg, 0.36 mmol), [3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methanol (103 mg, 0.36 mmol), triphenyl phosphine (94 mg, 0.36 mmol), diisopropyl azodicarboxylate (0.07 mL, 0.36 mmol) and dichloromethane (3.6 mL) were placed in a microwave reaction tube, sealed and heated in a microwave reactor to 100° C. for 10 minutes. The solution was concentrated then slurried in a 3:7 mixture of acetone: hexane. The resulting off-white solid was purified by chromatography (silica gel, 3:7 acetone:hexanes) to provide methyl 6-[4-({[3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (0.10 g, 52%). 1H NMR (400 MHz, DMSO-d6): δ 8.81 (s, 2H), 8.55 (d, J=9 Hz, 1H), 8.29 (d, J=2 Hz, 1H), 8.18-8.10 (m, 3H), 7.74 (d, J=9 Hz, 2H), 6.89 (d, J=9 Hz, 2H), 4.97 (s, 2H), 3.94 (s, 3H), 3.49 (septet, 7 Hz, 1H), 1.34 (d, J=7 Hz, 6H). ESI-LCMS m/z 548 (M+H)+.

Workup

  1. customsealed
  2. concentrationThe solution was concentrated
  3. additionthen slurried in a 3:7 mixture of acetone
  4. customThe resulting off-white solid was purified by chromatography (silica gel, 3:7 acetone:hexanes)

Sources & evidence

ORD record
ord-7525224e8548473aa49bea11d7f1f01e
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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