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 1508511노트

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HRID 1508511 반응식
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

참가 물질

5

반응물 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

생성물 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

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
25 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6564c759834043ebb09888d95d7fcdeb
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221834B2

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