Methanesulfonyl chloride → HCID 67363649, compound

HRID 1671929Notes

Reaction equation

HRID 1671929 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[F:40])=[CH:20][C:5]2[C:6]([C:16]([NH:18]C)=[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.[CH3:41][S:42](Cl)(=[O:44])=[O:43].[CH3:46]S(NS(C)(=O)=O)(=O)=O>>[F:40][C:23]1[CH:24]=[CH:25][C:26]([C:28](=[O:39])[NH:29][C:30]2([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH2:31][CH2:32]2)=[CH:27][C:22]=1[C:21]1[C:2]([NH:1][S:42]([CH3:41])(=[O:44])=[O:43])=[CH:3][C:4]2[O:8][C:7]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)=[C:6]([C:16]([NH2:18])=[O:17])[C:5]=2[C:20]=1[CH3:46]

Participants

4

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 79296Methanesulfonamide, N-(methylsulfonyl)-HCID 59275406HCID 59275406, compound

Product 1

HCID 67363649HCID 67363649, compound

Procedure

Prepared from the coupling between 6-Amino-5-(2-fluoro-5-(1-phenylcyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide and methanesulfonyl chloride (N,N-diisopropylethylamine, ClCH2CH2Cl, r.t.), followed by hydrolysis of the intermediate N-(methylsulfonyl)methanesulfonamide (Cs2CO3, 1:5 H2O/1,4-dioxane, 90° C.). Purification 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: 6.70-7.25 min. (UV detection at 220 nm). 1H NMR (500 MHz, CD3OD) δ 8.00-7.95 (overlapping m, 4H), 7.83 (s, 1H), 7.66 (s, 1H), 7.35 (t, J=9.00, 1H), 7.30-7.27 (overlapping m, 6H), 7.18 (m, 1H), 2.94 (s, 3H), 2.88 (s, 3H), 1.37-1.35 (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)+=616.48, 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=6.57 min; Column: Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=5.80 min.

Workup

  1. customPurification 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. custom6.70-7.25 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

Sources & evidence

ORD record
ord-e8925f96258d4185b8ba67ed6f004a9e
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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