Trifluoroacetic acid → methyl 6-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-naphthoate

HRID 1473510ノート

反応式

HRID 1473510 の反応式
COC1C=C(OC)C=CC=1C[N:6]([C:24]1[S:28][N:27]=[CH:26][N:25]=1)[S:7]([C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[C:16]([C:20]([O:22][CH3:23])=[O:21])=[CH:15][CH:14]=[CH:13]2)(=[O:9])=[O:8].C(O)(C(F)(F)F)=O>C(Cl)Cl>[S:28]1[C:24]([NH:6][S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[C:16]([C:20]([O:22][CH3:23])=[O:21])=[CH:15][CH:14]=[CH:13]3)(=[O:9])=[O:8])=[N:25][CH:26]=[N:27]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 86687402methyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-naphthoate

生成物 1

HCID 86687564methyl 6-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-naphthoate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A 500-mL two-neck flask was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate D; 10 g, 19.22 mmol), palladium (ii) acetate (0.216 g, 0.961 mmol), and Xantphos (1.112 g, 1.922 mmol). Triethylamine (77 ml, 19.22 mmol), toluene (48.0 ml), and methanol (15.55 ml, 384 mmol) were added, and the reaction was fitted with a reflux condensor. The reaction was evacuated and back-filled with carbon monoxide three times, then the reaction was heated to 70° C. and stirred for four hours under an atmosphere of carbon monoxide. The reaction was filtered through a pad of diatomaceous earth, which was thoroughly washed with ethyl acetate. The filtrate was concentrated, triturated in ethyl acetate and filtered. The solids were collected and the filtrate was concentrated. The trituration procedure was repeated twice, and the solids resulting from each trituration were combined with the previously isolated material. After the third trituration, the mother liquor was purified via column chromatography (80 g silica gel column, gradient elution 0 to 50% EtOAc:Heptane). The clean product fractions were combined with the previously isolated material and the resulting slurry was concentrated to afford methyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-naphthoate as a light yellow solid. m/z (ESI) 500.3 (M+H)+. 60 mg of methyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-naphthoate was dissolved in 1 mL of DCM and TFA (0.1 ml, 1.298 mmol) was added. The reaction was stirred for 30 minutes at room temperature. The material was concentrated, dissolved in acetonitrile and loaded onto a Biotage Isolute® PEAX ion exchange column (Biotage AB, Uppsala, Sweden) (pre-wetted with acetonitrile). The column was flushed several times with acetonitrile, then the product was liberated by flushing the column several times with about 1M HCl solution in MeOH/EtOAc. The second filtrate was concentrated to afford methyl 6-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-naphthoate. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.90 (d, J=9.2 Hz, 1H), 8.60 (d, J=2.0 Hz, 1H), 8.53-8.44 (m, 2H), 8.29 (dd, J=1.3, 7.3 Hz, 1H), 7.96 (dd, J=2.1, 9.2 Hz, 1H), 7.76 (dd, J=7.3, 8.2 Hz, 1H), 3.95 (s, 3H). m/z (ESI) 350.1 (M+H)+.

後処理

  1. concentrationThe material was concentrated
  2. dissolutiondissolved in acetonitrile
  3. customThe column was flushed several times with acetonitrile
  4. customby flushing the column several times with about 1M HCl solution in MeOH/EtOAc
  5. concentrationThe second filtrate was concentrated

出典と根拠

ORDレコード
ord-f521151e06a14882aa69b95e28bc1099
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

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