Triphenylphosphine → Methyl 7-[4-({[5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylate

HRID 2423422Notes

Reaction equation

HRID 2423422 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH:22]1([C:26]2[O:30][N:29]=[C:28]([C:31]3[C:36]([Cl:37])=[CH:35][N:34]=[CH:33][C:32]=3[Cl:38])[C:27]=2[CH2:39]O)[CH2:25][CH2:24][CH2:23]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>[CH:22]1([C:26]2[O:30][N:29]=[C:28]([C:31]3[C:32]([Cl:38])=[CH:33][N:34]=[CH:35][C:36]=3[Cl:37])[C:27]=2[CH2:39][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:17]=[C:16]4[C:11]([CH:12]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[N:14]=[CH:15]4)=[CH:10][CH:9]=3)=[CH:6][CH:7]=2)[CH2:23][CH2:24][CH2:25]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 59321463Methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylateHCID 59321566[5-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol

Product 1

HCID 59321535Methyl 7-[4-({[5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylateYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylate (50 mg, 0.18 mmol), [5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol (54 mg, 0.18 mmol) and triphenylphosphine (52 mg, 0.20 mmol) in dichloromethane (1.5 mL) was added diisopropyl azodicarboxylate (0.035 mL, 0.20 mmol). The solution was heated in a microwave reactor at 90° C. for 10 minutes and allowed to stand at ambient temperature overnight. The next day the solution was adsorbed onto silica gel and purified by chromatography (first in 0-1.75% methanol in chloroform gradient elution then in 0-2% methanol in chloroform) to afford methyl 7-[4-({[5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylate as a white solid (39 mg, 39%). 1H-NMR (400 MHz, DMSO-d6) δ 9.33 (s, 1H), 8.59 (s, 3H), 8.12 (s, 1H), 8.00-7.94 (m, 2H), 7.58 (d, J=9 Hz, 2H), 6.84 (d, J=9 Hz, 2H), 4.79 (s, 2H), 4.04 (s, 3H), 3.87-3.79 (m, 1H), 2.64-2.54 (m, 2H), 2.50-2.35 (m, 2H), 2.19-2.00 (m, 2H).

Workup

  1. custompurified by chromatography (
  2. washfirst in 0-1.75% methanol in chloroform gradient elution

Sources & evidence

ORD record
ord-35c25e2c36454a468f7b30e20a4b9ef1
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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