Triethylamine → HCID 53380049, Verbindung

HRID 515225Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 515225
[F:1][C:2]1([F:26])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[N:20]=[C:19]([CH2:21]O)[CH:18]=[CH:17][CH:16]=3)=[CH:14][C:9]=2[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24].C(N(CC)CC)C.S(Cl)(C)(=O)=O.[CH3:39][S:40]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)(=[O:42])=[O:41].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[F:1][C:2]1([F:26])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:16]=[CH:17][CH:18]=[C:19]([CH2:21][N:46]4[CH2:47][CH2:48][N:43]([S:40]([CH3:39])(=[O:42])=[O:41])[CH2:44][CH2:45]4)[N:20]=3)=[CH:14][C:9]=2[N:8]([CH3:23])[S:7]1(=[O:25])=[O:24]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 7091611-(Methylsulfonyl)piperazineHCID 67413047HCID 67413047, Verbindung

Produkt 1

HCID 53380049HCID 53380049, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To (6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}pyridin-2-yl)methanol (25-1) (30 mg, 0.079 mmol, 1.0 eq) was dissolved in NMP (1 mL) and triethylamine (0.04 mL, 0.24 mmol, 3.0 eq) was added followed by mesyl chloride (0.008 mL, 0.1 mmol, 1.2 eq). After 10 minutes, 1-(methylsulfonyl)piperazine (28.6 mg, 0.17 mmol, 2.1 eq) and DIPEA (0.061 mL, 0.35 mmol, 4.4 eq) were added. The resulting mixture stirred at 80° C. for 10 minutes. The mixture was cooled and purified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier) to afford 1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}pyridin-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (25-2) as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.99 (s, 1 H); 7.98 (d, J=8.0 Hz, 1 H); 7.84 (dd, J=1.6, 8.4 Hz, 1 H); 7.77 (d, J=1.6 Hz, 1 H); 7.44 (dd, J=1.6, 6.0 Hz, 1 H); 7.13 (d, J=8.4 Hz, 1 H); 4.66 (s, 2 H); 3.97 (d, J=7.2 Hz, 2 H); 3.62 (brs, 8 H); 3.39 (s, 3 H); 2.99 (s, 3 H); 2.21 (m, 1 H); 1.65 (m, 1 H); 1.44 (m, 1 H). HRMS m/z (M+H) 528.1538 found, 528.1545 required.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. custompurified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier)

Quellen und Nachweise

ORD-Eintrag
ord-dd92d5a63c654801adfd6f96ccc0cfa1
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108937B2

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