Triethylamine → Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate

HRID 600549ノート

反応式

HRID 600549 の反応式
[CH3:1][S:2](Cl)(=[O:4])=[O:3].C(N(CC)CC)C.[N:13]1([C:17]([C:19]2[N:24]=[CH:23][C:22]([O:25][C:26]3[CH:27]=[C:28]([CH:39]=[C:40]([C:42](=[O:51])[NH:43][C:44]4[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=4)[CH:41]=3)[O:29][CH:30]([CH2:36][CH2:37][OH:38])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:21][CH:20]=2)=[O:18])[CH2:16][CH2:15][CH2:14]1>C(Cl)Cl>[N:13]1([C:17]([C:19]2[N:24]=[CH:23][C:22]([O:25][C:26]3[CH:27]=[C:28]([CH:39]=[C:40]([C:42](=[O:51])[NH:43][C:44]4[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=4)[CH:41]=3)[O:29][CH:30]([CH2:36][CH2:37][O:38][S:2]([CH3:1])(=[O:4])=[O:3])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:21][CH:20]=2)=[O:18])[CH2:14][CH2:15][CH2:16]1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59761144Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-hydroxy-butanoate2 回

生成物 1

HCID 86621533Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate収率 42%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Methanesulfonyl chloride (13 L, 0.16 mmol) and triethylamine (34 μL, 0.24 mmol) were added to a solution of ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-hydroxy-butanoate (Intermediate 28) (65 mg, 0.12 mmol) in DCM (5 mL) at 0° C. under nitrogen. The reaction was allowed to warm to RT and stirred for 2 hours. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate (10 mL) and brine (10 mL). The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (10 mL). The combined organics were dried (MgSO4), concentrated under reduced pressure and the residue purified by column chromatography on silica eluting with 0-10% methanol/DCM to give product (29 mg, 42%). 1H NMR δ (300 MHz, CDCl3) 1.23-1.30 (3H, m), 2.33-2.46 (4H, m), 2.56 (3H, s), 3.03 (3H, s), 4.22-4.29 (4H, m), 4.44-4.49 (2H, m), 4.71 (2H t), 4.87-4.91 (1H, m), 6.81 (1H t), 7.21 (1H t), 7.29 (1H t), 7.38-7.41 (1H, m), 8.13 (2H d), 8.34 (1H d), 8.42 (1H, s), 9.51 (1H, s); m/z 615 (M+H)+.

後処理

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue partitioned between ethyl acetate (10 mL) and brine (10 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer re-extracted with ethyl acetate (10 mL)
  5. dry with materialThe combined organics were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customthe residue purified by column chromatography on silica eluting with 0-10% methanol/DCM

出典と根拠

ORDレコード
ord-d3459a4f4e7a4e44ad0b828f51b67380
出典データセット
uspto-grants-2011_03
特許番号
US07902200B2

反応ノート

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