Pyridine → HCID 59275729, compound

HRID 1671946Notes

Reaction equation

HRID 1671946 reaction equation
[NH2:1][C:2]1[C:21]([C:22]2[CH:27]=[C:26]([C:28](=[O:39])[NH:29][C:30]3([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:32][CH2:31]3)[CH:25]=[CH:24][C:23]=2[CH3:40])=[CH:20][C:5]2[C:6]([C:16]([NH:18][CH3:19])=[O:17])=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[O:8][C:4]=2[CH:3]=1.N1C=CC=CC=1.[CH3:47][S:48](Cl)(=[O:50])=[O:49]>C(Cl)CCl.CO>[F:15][C:12]1[CH:11]=[CH:10][C:9]([C:7]2[O:8][C:4]3[CH:3]=[C:2]([NH:1][S:48]([CH3:47])(=[O:50])=[O:49])[C:21]([C:22]4[CH:27]=[C:26]([C:28](=[O:39])[NH:29][C:30]5([C:33]6[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=6)[CH2:32][CH2:31]5)[CH:25]=[CH:24][C:23]=4[CH3:40])=[CH:20][C:5]=3[C:6]=2[C:16]([NH:18][CH3:19])=[O:17])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 59275389HCID 59275389, compound

Product 1

HCID 59275729HCID 59275729, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 887MethanolSolvent

Procedure

To a mixture of 6-amino-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide (53.3 mg, 0.100 mmol) (crude) in ClCH2CH2Cl (1 ml) at r.t. under N2 was added pyridine (0.024 mL, 0.300 mmol). The mixture was then added a solution of methanesulfonyl chloride (22.88 mg, 0.200 mmol) in ClCH2CH2Cl (0.3 ml), and stirred for about 22 hours. The mixture was diluted with MeOH and purified 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: 6.75-7.37 min. (UV detection at 220 nm). 1H NMR (500 MHz, CD3OD) δ 7.98 (m, J=8.85, 5.19, 2H), 7.85 (dd, J=8.09, 1.98, 1H), 7.79 (s, 1H), 7.75 (d, J=1.53, 1H), 7.51 (s, 1H), 7.47 (d, J=7.93, 1H), 7.17 (m, 1H), 7.30-7.26 (overlapping m, 5H), 7.29 (s, 1H), 2.93 (s, 3H), 2.88 (s, 3H), 2.23 (s, 3H), 1.35 (appeared as d, 4H). 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)+=612.34, HPLC Rt=1.583 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=7.48 min; Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=6.24 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, Rt=11.46 min.

Workup

  1. custompurified by Shimadzu-VP preparative reverse phase HPLC
  2. customthe separation method
  3. customB=100, Gradient time=10 min
  4. customtime=12 min, Flow Rate=25 mL/min, Column
  5. customWaters-Sunfire 19×100 mm S5, Fraction Collection
  6. custom6.75-7.37 min. (UV detection at 220 nm)
  7. customB=100, Gradient time=2 min
  8. customtime=3 min, Flow Rate=4 ml/min, Column
  9. customB=100, Gradient time=15 min
  10. customtime=18 min, Flow Rate=1 ml/min, Column
  11. customB=100, Gradient time=15 min
  12. customtime=18 min, Flow Rate=1 ml/min, Column

Sources & evidence

ORD record
ord-fa1c2b7aee704a568258da9c7a93f569
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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