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 271996ノート

反応式

HRID 271996 の反応式
[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]

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-d7243880f1ac44ebab836bc856bcc8e9
出典データセット
uspto-grants-2008_11
特許番号
US07452992B2

反応ノート

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