Diisopropylethylamine → N-(tert-butyl)-5-{[6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-6-phenyl-1,3-oxazinan-3-yl]carbonyl}-4-chloro-2-fluorobenzenesulfonamide

HRID 271996Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 271996
[NH2:1][CH2:2][CH2:3][C:4]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([OH:15])[CH2:5][CH2:6][O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].[C:22]([NH:26][S:27]([C:30]1[C:31]([F:40])=[CH:32][C:33]([Cl:39])=[C:34]([CH:38]=1)[C:35](O)=[O:36])(=[O:29])=[O:28])([CH3:25])([CH3:24])[CH3:23].[CH:41](N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CO.C(Cl)Cl>[C:22]([NH:26][S:27]([C:30]1[CH:38]=[C:34]([C:35]([N:1]2[CH2:2][CH2:3][C:4]([CH2:5][CH2:6][O:7][Si:8]([C:11]([CH3:12])([CH3:13])[CH3:14])([CH3:9])[CH3:10])([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[O:15][CH2:41]2)=[O:36])[C:33]([Cl:39])=[CH:32][C:31]=1[F:40])(=[O:29])=[O:28])([CH3:25])([CH3:24])[CH3:23]

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167781635-[(Tert-butylamino)sulfonyl]-2-chloro-4-fluorobenzoic acidHCID 598359811-Amino-5-{[tert-butyl(dimethyl)silyl]oxy}-3-phenylpentan-3-ol

Produkt 1

HCID 69181515N-(tert-butyl)-5-{[6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-6-phenyl-1,3-oxazinan-3-yl]carbonyl}-4-chloro-2-fluorobenzenesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 1-amino-5{[tert-butyl(dimethyl)silyl]oxy}-3-phenylpentan-3-ol (278 mg, 0.9 mmol) and p-formaldehyde (300 mg, 10 mmol) in 9 mL MeOH was heated under reflux for 90 min. A 2 mL aliquot (0.2 mmol) was removed, filtered, and concentrated in vacuo. The residue was redissolved in 0.5 mL DMF and 1 mL CH2Cl2 and to this solution was added 5-[(tert-butylamino)sulfonyl]-2-chloro-4-fluorobenzoic acid (62 mg, 0.2 mmol), diisopropylethylamine (70 μL, 0.4 mmol) and HATU (114 mg, 0.3 mmol). After 5 h, saturated aqueous NaHCO3 was added, and the aqueous layer was extracted with CHCl3. The organic layers were pooled, dried (Na2SO4), concentrated and purified by chromatography (4:1 hex:EtOAc) to provide N-(tert-butyl)-5-{[6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-6-phenyl-1,3-oxazinan-3-yl]carbonyl}-4-chloro-2-fluorobenzenesulfonamide, which was used without further purification. The crude N-(tert-butyl)-5-{[6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-6-phenyl-1,3-oxazinan-3-yl]carbonyl}-4-chloro-2-fluorobenzenesulfonamide was stirred in a solution of 1 M TBAF in THF for 1.5 h, then washed with saturated aqueous NaHCO3 and purified by chromatography (2:1 EtOAc:hex) to provide N-(tert-butyl)-4-chloro-2-fluoro-5-{[6-(2-hydroxyethyl)-6-phenyl-1,3-oxazinan-3-yl]carbonyl}benzenesulfonamide (25.2 mg, 25%) as a clear oil. 1H NMR (400 MHz, CDCl3), δ 8.03 (d, 0.5H, J=7.3 Hz, rotamer), 7.70 (d, 0.5H, J=7.3 Hz, rotamer), 7.46-7.30 (m, 6H), 5.81 (d, 0.5H, J=10.4 Hz, rotamer), 4.98 (m, 0.5H, rotamer), 4.88 (m, 1H), 4.72-4.48 (m, 3H), 3.15 (m, 1H), 2.96 (m, 1H), 2.52-1.73 (m, 5H), 1.24 (m, 9H, rotamers); ESI-MS 497 (M−H).

Aufarbeitung

  1. temperatureunder reflux for 90 min
  2. customA 2 mL aliquot (0.2 mmol) was removed
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in 0.5 mL DMF
  6. extractionthe aqueous layer was extracted with CHCl3
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. custompurified by chromatography (4:1 hex:EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-d7243880f1ac44ebab836bc856bcc8e9
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07452992B2

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