Potassium Carbonate → 5-{[2-(4-Fluoro-phenyl)-5-iodo-3-methylcarbamoyl-furo[2,3-b]pyridin-6-yl]-methanesulfonyl-amino}-pentanoic acid methyl ester

HRID 2190161Notes

Reaction equation

HRID 2190161 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][C:10]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])=[C:11]([I:14])[CH:12]=2)[O:7][C:6]=1[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:34][CH2:35][CH2:36][CH2:37][C:38]([O:40][CH3:41])=[O:39]>CC(C)=O>[CH3:41][O:40][C:38](=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34][N:15]([C:10]1[N:9]=[C:8]2[O:7][C:6]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[C:5]([C:3](=[O:4])[NH:2][CH3:1])[C:13]2=[CH:12][C:11]=1[I:14])[S:16]([CH3:19])(=[O:18])=[O:17]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79557Methyl 5-bromovalerateHCID 580523242-(4-fluorophenyl)-5-iodo-N-methyl-6-(methylsulfonamido)furo[2,3-b]pyridine-3-carboxamide

Product 1

HCID 545752025-{[2-(4-Fluoro-phenyl)-5-iodo-3-methylcarbamoyl-furo[2,3-b]pyridin-6-yl]-methanesulfonyl-amino}-pentanoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

To 2-(4-Fluoro-phenyl)-5-iodo-6-methanesulfonylamino-furo[2,3-b]pyridine-3-carboxylic acid methylamide (300 mg, 0.613 mmol), K2CO3 (169 mg, 1.226 mmol), KI (1018 mg, 6.13 mmol), and methyl 5-bromopentanoate (250 μl, 1.747 mmol) is added acetone (3066 μl) and the reaction mixture is stirred at 60° C. overnight. The acetone is removed under N2 and the mixture is taken up in 2 mL 1:1:1 DMF/H2O/ACN and filtered with a 0.45μ PTFE filter. Purification is achieved by reverse phase HPLC with a C8 column with 40-80% MeOH (0.1% TFA)/H2O (0.1% TFA). MS (ESI) m/z 604.0 (M+1). Retention time=1.48 min, Method A. 1H NMR (400 MHz, CDCl3 d ppm 8.77 (s, 1H), 7.96 (t, 2H), 7.19-7.36 (m, 2H), 5.80 (br s, 1H), 3.68 (t, 2H), 3.54 (s, 3H), 3.14 (s, 3H), 2.97 (d, 3H), 2.29 (t, 2H), 1.69-1.79 (m, 2H), 1.42 (s, 2H)

Workup

  1. customThe acetone is removed under N2
  2. filtrationfiltered with a 0.45μ PTFE
  3. filtrationfilter
  4. customPurification

Sources & evidence

ORD record
ord-8c93d68b1abc49248e90cf0c0812b2ac
Source dataset
uspto-grants-2012_12
Patent number
US08324239B2

Reaction notes

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