Ethanol → Ethyl 3-{[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]amino}benzoate

HRID 589771Notes

Reaction equation

HRID 589771 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([S:10]([NH:13][C:14]3[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=3)[C:17]([OH:19])=[O:18])(=[O:12])=[O:11])=[C:7]([CH3:23])[C:6]=2[CH:24]=1.C(N1C=CN=C1)(N1[CH:31]=[CH:30]N=C1)=O.N1C=CC=CC=1.CCO.C(O)(C(F)(F)F)=O>CC#N.CS(C)=O.CC#N.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([S:10]([NH:13][C:14]3[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=3)[C:17]([O:19][CH2:30][CH3:31])=[O:18])(=[O:12])=[O:11])=[C:7]([CH3:23])[C:6]=2[CH:24]=1

Participants

8

Reactant 5

HCID 702EthanolHCID 1049Pyridine2×HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 569413063-{[(5-Chloro-3-methyl-1-benzothien-2-yl)sulfonyl]amino}benzoic acid2×

Product 1

HCID 66800002Ethyl 3-{[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]amino}benzoateYield 54%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 86584666DMSO MeCN waterSolvent

Conditions

Temperature
60 °C

Procedure

A reaction mixture containing 3-{[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-amino}benzoic acid (21 mg, 0.055 mmol) (Intermediate 19), 1,1′-carbonyldiimidazole (17 mg, 0.106 mmol) and pyridine (9 μL, 0.113 mmol) in MeCN (0.75 mL) was stirred at 60° C. for 30 min, and then a second portion of pyridine (5 μL, 0.062 mmol) was added. After additional 30 min of stirring at 60° C., EtOH (6 μL, 0.100 mmol) was added. The reaction mixture was stirred at 50° C. over night, and then diluted with DMSO/MeCN/water. TFA (50 μL) was added and the crude product was purified by reversed phase chromatography (ACE C8, 5 μm, 21×50 mm, flow 25 ml/min, gradient: 0.1% TFA in water/MeCN over 6 minutes). The title compound was obtained in 54% yield (12.2 mg). 1H NMR (500 MHz, CDCl3) δ ppm 1.34 (t, J=7.08 Hz, 3 H) 2.45 (s, 3 H) 4.33 (q, J=7.08 Hz, 2 H) 6.92 (s, 1 H) 7.36 (dd, J=8.04, 7.66 Hz, 1 H) 7.42 (ddd, J=8.04, 2.32, 1.17 Hz, 1 H) 7.44 (dd, J=8.70, 1.95 Hz, 1 H) 7.71 (d, J=8.70 Hz, 1 H) 7.71 (d, J=1.95 Hz, 1 H) 7.71-7.72 (m, 1 H) 7.84 (ddd, J=7.66, 1.48, 1.17 Hz, 1 H). MS (ESI+) m/z 410 [M+H]+.

Workup

  1. stirringAfter additional 30 min of stirring at 60° C.
  2. stirringThe reaction mixture was stirred at 50° C. over night
  3. customthe crude product was purified by reversed phase chromatography (ACE C8, 5 μm, 21×50 mm, flow 25 ml/min, gradient: 0.1% TFA in water/MeCN over 6 minutes)

Sources & evidence

ORD record
ord-3323cf30961c486dab38e30585c2c229
Source dataset
uspto-grants-2016_01
Patent number
US09233946B2

Reaction notes

Loading…