Methanol → (1S,2R)-1-ethyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylic acid

HRID 736826ノート

反応式

HRID 736826 の反応式
[CH2:1]([C@:3]1([C:31]([O:33]C)=[O:32])[CH2:7][CH2:6][CH2:5][C@H:4]1[NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)=[CH:14][CH:13]=1)(=[O:11])=[O:10])[CH3:2].[OH-].[Na+].CO.Cl.C(N(CC)CC)C>C1COCC1>[CH2:1]([C@:3]1([C:31]([OH:33])=[O:32])[CH2:7][CH2:6][CH2:5][C@H:4]1[NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)=[CH:14][CH:13]=1)(=[O:10])=[O:11])[CH3:2]

参加物

6

反応物 4

HCID 887MethanolHCID 11130Triethylamine hydrochlorideHCID 14798Sodium HydroxideHCID 86607917HCID 86607917、化合物

生成物 1

HCID 68817120(1S,2R)-1-ethyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Methyl (1S,2R)-1-ethyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylate (315 mg, 0.653 mmol) was combined with aqueous 5M sodium hydroxide solution (0.65 mL, 3.3 mmol) in THF, with MeOH added to homogenize the mixture. This solution was stirred at 50° C. for 5d, after which triethylamine hydrochloride (540 mg, 3.9 mmol) was added. The heterogeneous mixture was concentrated, and chased twice with methanol and twice with benzene to give (1S,2R)-1-ethyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylic acid as a white solid that was carried on without further purification. The solid was combined with BOP (349 mg, 0.790 mmol), hydroxylamine hydrochloride (100 mg, 1.43 mmol) and triethylamine (0.45 mL) in DMF (3 mL) and heated at 50° C. overnight. Additional BOP (362 mg, 0.819 mmol), hydroxylamine hydrochloride (150 mg, 2.1 mmol) and Et3N (0.3 mL) were then added and the reaction was stirred at 50° C. overnight. The reaction was still incomplete and more BOP (750 mg, 1.70 mmol), hydroxylamine hydrochloride (333 mg, 4.76 mol) and Et3N (0.6 mL) were added. After 5 h the reaction mixture was diluted with brine and extracted three times with ethyl acetate. The combined organic extracts were dried over Na2SO4, concentrated, and purified via HPLC, eluting with a gradient of 15-100% MeCN/H2O (10 min) to give (1S,2R)-N-hydroxy -1-ethyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxamide (162 mg, 0.331 mmol, 51%) as a colorless solid. LCMS (M−H): 1.81 min, 483.8; 1H NMR (400 MHz, ACETONITRILE-D3) δ ppm 0.67 (t, J=7.45 Hz, 3H) 1.08-1.20 (m, 2H) 1.31-1.42 (m, 2H) 1.49-1.60 (m, 3H) 1.82-1.87 (m, 2H) 2.56-2.58 (m, 3H) 3.19-3.28 (m, 1H) 5.49-5.52 (m, 2H) 6.23 (d, J=8.59 Hz, 1H) 7.08-7.13 (m, 2H) 7.42 (s, 1H) 7.48 (td, J=7.64, 1.39 Hz, 1H) 7.64 (ddd, J=8.40, 6.88, 1.39 Hz, 1H) 7.70-7.75 (m, 2H) 7.91 (m, 2H).

後処理

  1. additionadded
  2. concentrationThe heterogeneous mixture was concentrated

出典と根拠

ORDレコード
ord-a2019c6643cd4369843bbb63ee780015
出典データセット
uspto-grants-2009_09
特許番号
US07595327B2

反応ノート

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