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

HRID 2423426Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of [5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanol (51 mg, 0.18 mmol), methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylate (50 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 then allowed to stand overnight. The mixture was adsorbed onto silica gel and purified by chromatography (silica gel, 0-1.25% methanol in dichloromethane) to afford methyl 7-[4-({[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylate (54 mg, 55%). 1H-NMR (400 MHz, DMSO-d6) δ 9.39 (s, 1H), 8.63 (s, 1H), 8.44 (s, 1H), 8.29-8.14 (m, 2H), 7.75 (d, J=9 Hz, 2H), 7.61-7.50 (m, 3H), 6.96 (d, J=9 Hz, 2H), 4.94 (s, 2H), 3.91 (s, 3H), 2.50-2.46 (m, 1H), 1.21-1.14 (m, 4H).

Workup

custompurified by chromatography (silica gel, 0-1.25% methanol in dichloromethane)

Sources & evidence

ORD record: ord-e1991bff26b94b43ba4f6a4c9543dd49
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960552B2

Reaction notes

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