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

HRID 2423416Notes

Reaction equation

HRID 2423416 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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:41]1([C:45]2[O:49][N:48]=[C:47]([C:50]3[C:55]([Cl:56])=[CH:54][N:53]=[CH:52][C:51]=3[Cl:57])[C:46]=2[CH2:58]O)[CH2:44][CH2:43][CH2:42]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[CH:41]1([C:45]2[O:49][N:48]=[C:47]([C:50]3[C:51]([Cl:57])=[CH:52][N:53]=[CH:54][C:55]=3[Cl:56])[C:46]=2[CH2:58][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)[CH2:42][CH2:43][CH2:44]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 59321540Methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylateHCID 59321566[5-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol

Product 1

HCID 59321527Methyl 6-[4-({[5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 26.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate (0.10 mg, 0.36 mmol), triphenylphosphine (94 mg, 0.36 mmol) and [5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol (Example 9e) (0.11 mg, 0.36 mmol) in dichloromethane (2.5 mL) was added diisopropyl azodicarboxylate (0.064 mL, 0.36 mmol). The mixture was heated to 90° C. for 10 minutes and then allowed to stand overnight. The mixture was adsorbed onto silica gel and purified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution followed by further purification (silica gel, 0-30% ethyl acetate in hexanes gradient elution) to afford methyl 6-[4-({[5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (53 mg, 26%). 1H-NMR (400 MHz, DMSO-d6) δ 8.81 (s, 2H), 8.55 (d, J=9 Hz, 1H), 8.28 (s, 1H), 8.18-8.10 (m, 3H), 7.73 (d, J=9 Hz, 2H), 6.88 (d, J=9 Hz, 2H), 4.93 (s, 2H), 4.08-3.99 (m, 1H), 3.94 (s, 3H), 2.45-2.34 (m, 4H), 2.15-2.02 (m, 1H), 1.99-1.89 (m, 1H).

Workup

  1. custompurified by chromatography (
  2. washsilica gel, 0-40% ethyl acetate in hexanes gradient elution
  3. customfollowed by further purification (silica gel, 0-30% ethyl acetate in hexanes gradient elution)

Sources & evidence

ORD record
ord-490debe964c94d55b586c42a35edbb7c
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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