N-Piperidinoethanol → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(piperidin-1-yl)ethyl)pyrrolidine-3-carboxylic acid

HRID 61379

Reaktionsgleichung

O[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=[O:21].C([NH:27][C@:28]1([C:45](NC(C)(C)C)=[O:46])[C@@H:32]([CH2:33][CH2:34][CH2:35][B:36]2[O:40]C(C)(C)C(C)(C)[O:37]2)[CH2:31][NH:30][CH2:29]1)(=O)C>C(#N)C>[NH2:27][C@:28]1([C:45]([OH:46])=[O:21])[C@@H:32]([CH2:33][CH2:34][CH2:35][B:36]([OH:37])[OH:40])[CH2:31][N:30]([CH2:2][CH2:3][N:4]2[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]2)[CH2:29]1

Komponenten

Reaktionsbedingungen

Temperatur: 60 °C

Versuchsvorschrift

A cooled (0° C.) solution of N-(2-hydroxyethyl)piperidine (90.5 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 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-(piperidin-1-yl)ethyl)pyrrolidine-3-carboxylic acid (140 mg, 64%) as a glassy colorless solid. NMR (D2O) δ 3.85-4.05 (m, 2 H), 3.65-3.80 (m, 3 H), 3.35-3.55 (m, 5 H), 2.85-3.00 (m, 2 H), 2.60 (m, 1 H), 1.80-1.95 (m, 2 H), 1.55-1.75 (m, 4 H), 1.10-1.50 (m, 4 H), 0.63-0.73 (m, 2 H). MS (m+1): 328.3; MS (m−H2O+1): 310.0.

Aufarbeitung

concentrationThe reaction mixture was concentrated
customisolated

Quellen und Nachweise

ORD-Eintrag: ord-d90d9bdbecc94d978241df722b8ac047
Quelldatensatz: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09440995B2

Verknüpfte Notizen

Wird geladen…