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

HRID 1473509
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1473509
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([N:15]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1[O:30][CH3:31])[C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2.CC1(C)C2[C:54](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:53][C:35]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(N(CC)CC)C.C[OH:82]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:31][O:30][C:23]1[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:22]=1[CH2:21][N:15]([C:16]1[S:20][N:19]=[CH:18][N:17]=1)[S:12]([C:6]1[CH:7]=[C:8]2[C:3](=[CH:4][CH:5]=1)[C:2]([C:35]([O:53][CH3:54])=[O:82])=[CH:11][CH:10]=[CH:9]2)(=[O:13])=[O:14]
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Komponenten

7

Edukt 4

HCID 887MethanolHCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866873455-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide2×

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

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)+.

Aufarbeitung

  1. customthe reaction was fitted with a reflux condensor
  2. customThe reaction was evacuated
  3. additionback-filled with carbon monoxide three times
  4. filtrationThe reaction was filtered through a pad of diatomaceous earth, which
  5. washwas thoroughly washed with ethyl acetate
  6. concentrationThe filtrate was concentrated
  7. customtriturated in ethyl acetate
  8. filtrationfiltered
  9. customThe solids were collected
  10. concentrationthe filtrate was concentrated
  11. customthe solids resulting from each trituration
  12. customAfter the third trituration, the mother liquor was purified via column chromatography (80 g silica gel column, gradient elution 0 to 50% EtOAc:Heptane)
  13. concentrationthe resulting slurry was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-839051f0d79b4990b2d190780a9b30b0
Quelldatensatz
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09012443B2

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