N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-({3-[(1,1-dimethylethyl)oxy]propanoyl}amino)-1H-indole-2-carboxamide → N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-[(3-hydroxypropanoyl)amino]-1H-indole-2-carboxamide

HRID 1875027Notes

Reaction equation

HRID 1875027 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([NH:21][C:22](=[O:30])[CH2:23][CH2:24][O:25]C(C)(C)C)=[CH:16][CH:15]=3)=[O:11])=[C:4]([F:31])[C:3]=1[O:32][C:33]1[CH:38]=[C:37]([C:39]#[N:40])[CH:36]=[C:35]([Cl:41])[CH:34]=1>Cl.O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([NH:21][C:22](=[O:30])[CH2:23][CH2:24][OH:25])=[CH:16][CH:15]=3)=[O:11])=[C:4]([F:31])[C:3]=1[O:32][C:33]1[CH:38]=[C:37]([C:39]#[N:40])[CH:36]=[C:35]([Cl:41])[CH:34]=1

Participants

4

Reactant 1

HCID 59451555N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-({3-[(1,1-dimethylethyl)oxy]propanoyl}amino)-1H-indole-2-carboxamide

Product 1

HCID 59451632N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-[(3-hydroxypropanoyl)amino]-1H-indole-2-carboxamideYield 19.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-({3-[(1,1-dimethylethyl)oxy]propanoyl}amino)-1H-indole-2-carboxamide (0.040 g, 0.067 mmol) was dissolved in 4N HCl in dioxane (3 mL). The solution was heated at 100° C. overnight. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA) to give the title compound (0.007 g, 19%) as a white powder. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.49 (br. s., 1H), 9.70 (s, 1H), 8.67-9.07 (m, 1H), 7.95 (s, 1H), 7.77 (s, 1H), 7.42-7.53 (m, 2H), 7.37 (d, 1H), 7.25-7.32 (m, 1H), 7.19-7.25 (m, 1H), 7.06 (s, 1H), 4.52 (d, 2H), 3.62-3.73 (m, 2H), 3.51-3.60 (m, 1H), 2.40 (t, 2H). ES MS: m/z 541 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solvent was evaporated
  3. customThe residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA)

Sources & evidence

ORD record
ord-8dcf2e35e28f4c1faf777ea41cfa537c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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