Triphenylphosphine → Methyl 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylate

HRID 2423456Notes

Reaction equation

HRID 2423456 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.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]([CH2:50][O:51][C:52]3[C:57]([CH3:58])=[CH:56][CH:55]=[CH:54][C:53]=3[CH3:59])[C:46]=2[CH2:60]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]([CH2:50][O:51][C:52]3[C:53]([CH3:59])=[CH:54][CH:55]=[CH:56][C:57]=3[CH3:58])[C:46]=2[CH2:60][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)[CH2:42][CH2:43][CH2:44]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 59321463Methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylateHCID 59321504(5-Cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methanol

Product 1

HCID 59321545Methyl 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylateYield 58.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylate (90 mg, 0.32 mmol), triphenylphosphine (93 mg, 0.35 mmol), and (5-cyclobutyl-3-{[(2,6-dimethyl phenyl)oxy]methyl}-4-isoxazolyl)methanol (93 mg, 0.32 mmol) in dichloromethane (1.5 mL) was added diisopropyl azodicarboxylate (0.064 mL, 0.35 mmol) dropwise. The solution was heated in a microwave reactor at 90° C. for 10 minutes. The solution was concentrated, adsorbed onto silica gel and purified by chromatography (silica gel, 0-25% acetone in hexanes gradient elution) to afford methyl 7-(4-{[(5-cyclobutyl-3-{[(2,6-dimethylphenyl)oxy]methyl}-4-isoxazolyl)methyl]oxy}phenyl)-3-isoquinolinecarboxylate (103 mg, 58%). 1H-NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 8.64 (s, 1H), 8.50 (s, 1H), 8.26-8.19 (m, 2H), 7.85 (d, J=9 Hz, 2H), 7.16 (d, J=9 Hz, 2H), 7.00-6.90 (m, 3H), 5.06 (s, 2H), 4.90 (s, 2H), 3.99-3.90 (m, 1H), 3.91 (s, 3H), 2.37-2.30 (m, 4H), 2.14 (s, 6H), 2.09-2.01 (m, 1H), 1.98-1.89 (m, 1H).

Workup

  1. concentrationThe solution was concentrated
  2. custompurified by chromatography (silica gel, 0-25% acetone in hexanes gradient elution)

Sources & evidence

ORD record
ord-8957860392af485097b447d2c5d59368
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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