Tetrahydrofuran → (S)-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)(cyclopentyl)methanone

HRID 1483946Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1483946
Cl.[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C@H:17]3[CH2:22][CH2:21][CH2:20][NH2+:19][CH2:18]3)=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:10])(=[O:9])[N:8]=1.C1COCC1.C([O-])(O)=O.[Na+].[CH:33]1([C:38](Cl)=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34]1>O>[NH2:2][C:3]1[C:4]2[C:14]([O:15][CH2:16][C@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:38]([CH:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)=[O:39])[CH2:18]3)=[CH:13][CH:12]=[CH:11][C:5]=2[NH:6][S:7](=[O:9])(=[O:10])[N:8]=1

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 78284Cyclopentanecarbonyl chlorideHCID 516892Sodium Bicarbonate2×HCID 86714280(S)-3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidinium hydrochloride

Produkt 1

HCID 73213589(S)-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)(cyclopentyl)methanoneAusbeute 52,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a solution of (S)-3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidinium hydrochloride (Example 2a, 528 mg, 1.52 mmol) in H2O:THF (20 mL, 2:1), was added NaHCO3 (640 mg, 7.60 mmol). Upon complete dissolution of the NaHCO3, cyclopentanecarbonyl chloride (945 uL, 7.60 mmol) was added dropwise. The reaction was stirred at room temperature overnight. The precipitate was collected by vacuum filtration and purified by preparative HPLC (10-90% acetonitrile in water). The pure fractions were combined, concentrated then dissolved in a solution of NaHCO3 (250 mg in 10 mL water). After complete dissolution, the mixture was cooled in an ice bath and neutralized with 1N HCl. The resulting white solid was collected by vacuum filtration to provide the desired product (322 mg, 52%) as a white solid. H NMR (DMSO-d6, 400 MHz, 80° C.): 1.43 (m, 2H), 1.51-1.80 (m, 10H), 1.90 (m, 1H), 2.09 (m, 1H), 2.96 (m, 2H), 4.01 (br m, 2H), 4.12 (d, J=6.4 Hz, 2H), 6.67 (d, J=7.8 Hz, 1H), 6.77 (d, J=8.3 Hz, 1H), 7.46 (t, J=8.3 Hz, 1H), 7.92 (br s, 2H), 10.70 (br s, 1H). MS=407 (MH+).

Aufarbeitung

  1. additionwas added dropwise
  2. filtrationThe precipitate was collected by vacuum filtration
  3. custompurified by preparative HPLC (10-90% acetonitrile in water)
  4. concentrationconcentrated
  5. dissolutionthen dissolved in a solution of NaHCO3 (250 mg in 10 mL water)
  6. dissolutionAfter complete dissolution
  7. temperaturethe mixture was cooled in an ice bath
  8. filtrationThe resulting white solid was collected by vacuum filtration

Quellen und Nachweise

ORD-Eintrag
ord-33b3544d4ac743aeb110da976348d743
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09420814B2

Notizen zur Reaktion

Wird geladen…