Diisopropylcarbodiimide → 3-Butyl-4-[4-cyclohexyloxy-3-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-6-(1-methyl-piperidin-4-yloxy)-pyridazine

HRID 1972040Notes

Reaction equation

HRID 1972040 reaction equation
[CH2:1]([C:5]1[N:6]=[N:7][C:8]([O:32][CH:33]2[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]2)=[CH:9][C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[C:15]([CH:24]=1)[C:16]([NH:18][C:19]([CH3:23])([CH3:22])[CH2:20]O)=[O:17])[CH2:2][CH2:3][CH3:4].C(N=C=NC(C)C)(C)C>FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O.O1CCOCC1>[CH2:1]([C:5]1[N:6]=[N:7][C:8]([O:32][CH:33]2[CH2:34][CH2:35][N:36]([CH3:39])[CH2:37][CH2:38]2)=[CH:9][C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([O:25][CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]2)=[C:15]([C:16]2[O:17][CH2:20][C:19]([CH3:22])([CH3:23])[N:18]=2)[CH:24]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 2

HCID 12734Diisopropylcarbodiimide2×HCID 673756195-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzamide

Product 1

HCID 584383623-Butyl-4-[4-cyclohexyloxy-3-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-6-(1-methyl-piperidin-4-yloxy)-pyridazineYield 59.4%

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzamide (0.163 mmol, 87.7 mg), copper(II) trifluoromethanesulfonate (0.01 mmol, 3.6 mg), N,N′-diisopropylcarbodiimide (0.163 mmol, 20.6 mg) and dioxane (1 mL) was heated at 100° C. for 1 h. Copper(II) trifluoromethanesulfonate (0.01 mmol, 3.6 mg) and N,N′-diisopropylcarbodiimide (0.163 mmol, 20.6 mg) were added again and the reaction mixture was heated at 100° C. for another 1 h. The crude material was purified by column chromatography on basic alumina using 10-80% ethyl acetate in DCM to provide 3-butyl-4-[4-cyclohexyloxy-3-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-6-(1-methyl-piperidin-4-yloxy)-pyridazine (50.4 mg). LCMS: m/z 522 [M+1] 1H NMR (400 MHz, CDCl3) δ 7.61 (1H, s), 7.31 (1H, d), 7.05 (1H, dd), 6.79 (1H, d), 5.39 (1H, bs), 4.41 (1H, bs), 4.18 (4H, bs), 4.11 (3H, s), 3.41-3.97 (6H, m), 1.13-2.89 (22H, m), 0.84 (3H, t).

Workup

  1. temperaturethe reaction mixture was heated at 100° C. for another 1 h
  2. customThe crude material was purified by column chromatography on basic alumina using 10-80% ethyl acetate in DCM

Sources & evidence

ORD record
ord-ca959fd6a6a3482792bbd6cef5f3400f
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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