Hydrochloric Acid → HCID 59275199, compound

HRID 1025150Notes

Reaction equation

HRID 1025150 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([NH:21][S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:26]4[CH:31]=[C:30]([C:32](=[O:43])[NH:33][C:34]5([C:37]6[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=6)[CH2:36][CH2:35]5)[CH:29]=[CH:28][C:27]=4[CH3:44])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.Br[CH2:46][CH2:47][O:48][Si](C(C)(C)C)(C)C.Cl>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH2:46][CH2:47][OH:48])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:26]4[CH:31]=[C:30]([C:32](=[O:43])[NH:33][C:34]5([C:37]6[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=6)[CH2:35][CH2:36]5)[CH:29]=[CH:28][C:27]=4[CH3:44])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 59275729HCID 59275729, compound

Product 1

HCID 59275199HCID 59275199, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-(4-fluorophenyl)-6-(N-(2-hydroxyethyl)methylsulfonamido)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide was prepared from the alkylation of 2-(4-Fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)-6-(methylsulfonamido)benzofuran-3-carboxamide using (2-bromoethoxy)(tert-butyl)dimethylsilane (K2CO3, DMF 55° C.) followed by deprotection using HCl in 1,4-dioxane at r.t. Purification was preformed by Shimadzu-VP preparative reverse phase HPLC using the separation method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=50, Final % B=100, Gradient time=10 min, Stop time=12 min, Flow Rate=25 mL/min, Column: Waters-Sunfire 19×100 mm S5, Fraction Collection: 6.32-6.81 min. (UV detection at 220 nm). LC/MS were performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Stop time=3 min, Flow Rate=4 ml/min, Column: Xterra MS 7 um, C18, 3.0×50 mm; (ES+) m/z (M+H)+=656.06, HPLC Rt=1.563 min. Analytical HPLC were performed by using Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: Solvent A=5% MeCN-95% H2O-0.1% TFA, Solvent B=95% MeCN-5% H2O-0.1% TFA, Start % B=50, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min, Column: Sunfire C18, 3.5 um, 4.6×150 mm, Rt=6.05 min; Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=5.38 min. Analytical HPLC method: Solvent A=5% MeOH-95% H2O-10 mM NH4HCO3, Solvent B=95% MeOH-5% H2O-10 mM NH4HCO3, Start % B=50, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min, Column: Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=11.42 min.

Workup

  1. customat r.t
  2. customPurification
  3. customthe separation method
  4. customB=100, Gradient time=10 min
  5. customtime=12 min, Flow Rate=25 mL/min, Column
  6. customWaters-Sunfire 19×100 mm S5, Fraction Collection
  7. custom6.32-6.81 min. (UV detection at 220 nm)
  8. customB=100, Gradient time=2 min
  9. customtime=3 min, Flow Rate=4 ml/min, Column
  10. customB=100, Gradient time=15 min
  11. customtime=18 min, Flow Rate=1 ml/min, Column
  12. customB=100, Gradient time=15 min
  13. customtime=18 min, Flow Rate=1 ml/min, Column

Sources & evidence

ORD record
ord-e256addcb2ba4c9ba2ca897bfef988bd
Source dataset
uspto-grants-2014_05
Patent number
US08722688B2

Reaction notes

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