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 1508511ノート

反応式

HRID 1508511 の反応式
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

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
25 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6564c759834043ebb09888d95d7fcdeb
出典データセット
uspto-grants-2015_12
特許番号
US09221834B2

反応ノート

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