Diiodomethane → (4S,5R)-3-{[6-azetidin-1-yl-3-(5-iodo-2-methoxyphenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1508511Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1508511
N[C:2]1[CH:3]=[CH:4][C:5]([O:40][CH3:41])=[C:6]([C:8]2[C:9]([CH2:18][N:19]3[C@@H:23]([CH3:24])[C@@H:22]([C:25]4[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=4)[O:21][C:20]3=[O:39])=[N:10][C:11]([N:14]3[CH2:17][CH2:16][CH2:15]3)=[CH:12][CH:13]=2)[CH:7]=1.[I:42]CI.N(OCCC(C)C)=O>C1(C)C=CC=CC=1>[N:14]1([C:11]2[N:10]=[C:9]([CH2:18][N:19]3[C@@H:23]([CH3:24])[C@@H:22]([C:25]4[CH:30]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:28]=[C:27]([C:35]([F:37])([F:38])[F:36])[CH:26]=4)[O:21][C:20]3=[O:39])[C:8]([C:6]3[CH:7]=[C:2]([I:42])[CH:3]=[CH:4][C:5]=3[O:40][CH3:41])=[CH:13][CH:12]=2)[CH2:15][CH2:16][CH2:17]1

Komponenten

5

Edukt 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 86704602(4S,5R)-3-{[3-(5-amino-2-methoxyphenyl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Produkt 1

HCID 86704603(4S,5R)-3-{[6-azetidin-1-yl-3-(5-iodo-2-methoxyphenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of (4S,5R)-3-{[3-(5-amino-2-methoxyphenyl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (460 mg, 0.792 mmol) in toluene (7 mL) and diiodomethane (2 mL, 24.79 mmol) was added isoamyl nitrite (0.213 mL, 1.585 mmol) dropwise at room temperature. The mixture was stirred at 25° C. for 15 min. Then the mixture was heated at 80° C. for 45 min. The reaction mixture was loaded on a silica column directly and was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 270 mL, gradient to 35% EtOAc in hexanes over 972 mL) to afford (4S,5R)-3-{[6-azetidin-1-yl-3-(5-iodo-2-methoxyphenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=691.1. found=692.0 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.87 (s, 1H); 7.75 (s, 2H); 7.62 (dd, J=8.7, 2.2 Hz, 1H); 7.54-7.38 (m, 1H); 7.29 (d, J=8.3 Hz, 1H); 6.74 (d, J=8.7 Hz, 1H); 6.28 (d, J=8.3 Hz, 1H); 5.75-5.30 (m, 1H); 4.81 (d, J=16.3 Hz, 1H); 4.21-4.00 (m, 6H); 3.79 (s, 3H); 2.48-2.38 (m, 2H); 0.67 (s, br, 3H).

Aufarbeitung

  1. temperatureThen the mixture was heated at 80° C. for 45 min
  2. customwas purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 270 mL, gradient to 35% EtOAc in hexanes over 972 mL)

Quellen und Nachweise

ORD-Eintrag
ord-6564c759834043ebb09888d95d7fcdeb
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221834B2

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