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

HRID 2423464Notes

Reaction equation

HRID 2423464 reaction equation
O[CH2:2][C:3]1[C:7]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[N:22]=[C:21]([C:26]([O:28][CH3:29])=[O:27])[CH:20]=[CH:19]4)=[CH:12][CH:11]=2)=[C:6]([CH:30]([CH3:32])[CH3:31])[O:5][N:4]=1.[Cl:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=1[NH:41][C:42](=[O:47])[C:43]([F:46])([F:45])[F:44].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[Cl:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=1[N:41]([CH2:2][C:3]1[C:7]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[N:22]=[C:21]([C:26]([O:28][CH3:29])=[O:27])[CH:20]=[CH:19]4)=[CH:12][CH:11]=2)=[C:6]([CH:30]([CH3:32])[CH3:31])[O:5][N:4]=1)[C:42](=[O:47])[C:43]([F:45])([F:46])[F:44]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 3358365N-(2,6-dichlorophenyl)-2,2,2-trifluoroacetamideHCID 59321462Methyl 6-[4-({[3-(hydroxymethyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

Product 1

HCID 59321544Methyl 6-[4-({[3-{[(2,6-dichlorophenyl)(trifluoroacetyl)amino]methyl}-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 6-[4-({[3-(hydroxymethyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (25 mg, 0.058 mmol), N-(2,6-dichlorophenyl)-2,2,2-trifluoroacetamide (15 mg, 0.058 mmol) and triphenylphosphine (30 mg, 0.12 mmol) in dichloromethane was added di-tert-butyl azodicarboxylate (27 mg, 0.12 mmol). The solution was stirred at ambient temperature for approximately 1.5 hours and then was adsorbed onto silica gel and purified by chromatography (silica gel, 0-100% ethyl acetate in hexanes gradient elution). The resulting mixture was further purified by chromatography (silica gel, 2% methanol in dichloromethane) to afford methyl 6-[4-({[3-{[(2,6-dichlorophenyl)(trifluoroacetyl)amino]methyl}-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (10 mg, 26%). 1H-NMR (400 MHz, CDCl3) δ 8.36-8.33 (m, 2H), 8.22 (d, J=9 Hz, 1H), 8.06-8.01 (m, 2H), 7.71 (d, J=9 Hz, 2H), 7.42-7.29 (m, 3H), 7.11 (d, J=9 Hz, 2H), 5.05 (s, 2H), 5.04 (s, 2H), 4.05 (s, 3H), 3.27 (septet, J=7 Hz, 1H), 1.34 (d, J=7 Hz, 6H). LRMS (APCI) m/z 672 (M+H)+.

Workup

  1. custompurified by chromatography (silica gel, 0-100% ethyl acetate in hexanes gradient elution)
  2. customThe resulting mixture was further purified by chromatography (silica gel, 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9d3175f38eaa41f98bcdc66c96b38ab1
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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