Potassium Carbonate → HCID 69630218, compound

HRID 1792844Notes

Reaction equation

HRID 1792844 reaction equation
[C:1]1([S:7]([NH:10][CH:11]([CH2:25][C:26]2[CH:34]=[C:33]([Cl:35])[C:32]([OH:36])=[C:31]3[C:27]=2[CH:28]=[N:29][NH:30]3)[C:12]([NH:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:13])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:44][C:45]([O:47]C)=[O:46]>CN(C=O)C.CCOC(C)=O>[C:1]1([S:7]([NH:10][CH:11]([C:12](=[O:13])[NH:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][C:26]2[CH:34]=[C:33]([Cl:35])[C:32]([O:36][CH2:44][C:45]([OH:47])=[O:46])=[C:31]3[C:27]=2[CH:28]=[N:29][NH:30]3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 22025332HCID 22025332, compound

Product 1

HCID 69630218HCID 69630218, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Benzenesulfonylamino-3-(6-chloro-7-hydroxy-1H-indazol-4-yl)-N-(4-phenyl-butyl)-propionamide (30 mg, 0.057 mmol) is dissolved in DMF (1 mL) and K2CO3 is added followed by a slight excess of methyl bromoacetate (11 mg, 0.072 mmol). The reaction is allowed to stir for 36 h. The reaction is worked-up by diluting with EtOAc and washing with NH4Cl, 0.5 N HCl, water and brine. The solution is dried with MgSO4 and concentrated to provide a mixture of the intermediate ester and desired acid product as observed by LC/MS. The acid is purified by chromatography using a 10 g C18 sep-pak column (CH3CN/H2O) to provide {4-[2-benzenesulfonylamino-2-(4-phenyl-butylcarbamoyl)-ethyl]-6-chloro-1H-indazol-7-yloxy}-acetic acid. 1H NMR (500 MHz, DMSO-d6) δ 8.17 (d, 1H), 8.29 (bs, 1H), 7.94 (dd, 1H), 7.46 (d, 2H), 7.42 (dd, 1H), 7.28–7.24 (m, 4H), 7.16–7.14 (m, 3H), 6.84 (s, 1H), 4.59 (bs, 2H), 4.19–4.15 (m, 1H), 4.01–3.95 (m, 1H), 3.03–2.97 (m, 1H), 2.90–2.79 (m, 3H), 2.50 (obs, 2H), 1.43–1.38 (m, 2H), 1.22–1.17 (m, 2H); MS (ESI+) m/z 585 (M+H).

Workup

  1. washwashing with NH4Cl, 0.5 N HCl, water and brine
  2. dry with materialThe solution is dried with MgSO4
  3. concentrationconcentrated
  4. customto provide
  5. customThe acid is purified by chromatography

Sources & evidence

ORD record
ord-dac15edfccee490a90f39607a30309f9
Source dataset
uspto-grants-2006_07
Patent number
US07078425B2

Reaction notes

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