Hydrochloric Acid → 2-(4-(4-(2,4-Dichlorophenylsulfonamido)-1H-indazol-5-yloxy)-3-methoxyphenyl)acetic acid

HRID 2423313Notes

Reaction equation

HRID 2423313 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:21]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][C:30]([O:32]C)=[O:31])=[CH:25][C:24]=2[O:34][CH3:35])=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[N:16][N:17]2COCC[Si](C)(C)C)(=[O:11])=[O:10].Cl>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:21]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][C:30]([OH:32])=[O:31])=[CH:25][C:24]=2[O:34][CH3:35])=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[N:16][NH:17]2)(=[O:10])=[O:11]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 59864905methyl 2-(4-(4-(2,4-dichlorophenylsulfonamido)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yloxy)-3-methoxyphenyl)acetate

Product 1

HCID 598647692-(4-(4-(2,4-Dichlorophenylsulfonamido)-1H-indazol-5-yloxy)-3-methoxyphenyl)acetic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of methyl 2-(4-(4-(2,4-dichlorophenylsulfonamido)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yloxy)-3-methoxyphenyl)acetate (45 mg, 0.06 mmol) in ethanol (2 mL) was added 6N aqueous hydrochloric acid (1 mL). The resulting solution was heated at reflux for 3 h. After that time the mixture was cooled to room temperature and concentrated under reduced pressure and the residue taken up in THF (3 mL) and an excess of 2N aqueous lithium hydroxide added. The mixture was stirred at reflux for 1 h, then cooled to room temperature. The mixture was concentrated under reduced pressure. Column chromatography of the residue (1-5% MeOH/DCM with 0.1% AcOH) afforded the product as a cream solid. LC-MS ESI (pos.) m/e: 523 (M+H). 1H NMR (500 MHz) (d6DMSO) δ 11.20 (s, 1H); 10.25 (s, 1H); 7.96 (s, 1H); 7.68 (d, J=8 Hz, 1H); 7.56 (s, 1H), 7.35 (m, 2H); 6.93 (s, 1H), 6.70 (d, J=9 Hz, 1H); 6.61 (d, J=8 Hz, 1H); 6.24 (d, J=9 Hz, 1H); 3.70 (s, 3H); 3.55 (s, 2H).

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureat reflux for 3 h
  3. concentrationconcentrated under reduced pressure
  4. additionan excess of 2N aqueous lithium hydroxide added
  5. temperatureat reflux for 1 h
  6. temperaturecooled to room temperature
  7. concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-e062ee22b91149949b9514f1c5ed6601
Source dataset
uspto-grants-2011_06
Patent number
US07960567B2

Reaction notes

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