Diethylethanolamine → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(diethylamino)ethyl)pyrrolidine-3-carboxylic acid

HRID 61380

反応式

C(N(CC)CC[OH:6])C.[CH:9]([N:12]([CH:15]([CH3:17])C)[CH2:13][CH3:14])([CH3:11])C.CS(Cl)(=O)=O.C([NH:26][C@:27]1([C:44](NC(C)(C)C)=[O:45])[C@@H:31]([CH2:32][CH2:33][CH2:34][B:35]2[O:39]C(C)(C)C(C)(C)[O:36]2)[CH2:30][NH:29][CH2:28]1)(=O)C>C(#N)C>[NH2:26][C@:27]1([C:44]([OH:45])=[O:6])[C@@H:31]([CH2:32][CH2:33][CH2:34][B:35]([OH:36])[OH:39])[CH2:30][N:29]([CH2:17][CH2:15][N:12]([CH2:9][CH3:11])[CH2:13][CH3:14])[CH2:28]1

参加物

反応条件

温度: 60 °C

実験手順

A cooled (0° C.) solution of N,N-diethylethanolamine (82 mg, 0.70 mmol) and diisopropylethylamine (0.30 mL, 1.7 mmol) in anhydrous acetonitrile (12 mL) under nitrogen was treated with methanesulfonyl chloride (80.2 mg, 0.70 mmol), stirred 2.5 h, and treated with (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and heated to 60° C. for 15 h. The reaction mixture was concentrated, deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(diethylamino)ethyl)pyrrolidine-3-carboxylic acid (120 mg, 57%) as a white foam. NMR (D2O) δ 3.97 (d, J=12.5 Hz, 1 H), 3.87 (m, 1 H), 3.65-3.80 (m, 3 H), 3.35-3.55 (m, 3 H), 3.19 (q, J=7.5 Hz, 4 H), 2.55-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.20 (t, J=7.5 Hz, 6 H), 1.15-1.35 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m−H2O+1): 298.3; MS (m−2 H2O+1): 280.1.

後処理

concentrationThe reaction mixture was concentrated
customisolated

出典と根拠

ORDレコード: ord-3802a3036e4f4e3da033322a29b8350f
出典データセット: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US09440995B2

反応式

参加物

反応物 4

生成物 1

試薬・触媒・溶媒 1

反応条件

実験手順

後処理

出典と根拠

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