Methanesulfonyl chloride → (3R,4S)-3-amino-4-(3-boronopropyl)-1-((1-methylpiperidin-2-yl)methyl)pyrrolidine-3-carboxylic acid

HRID 590725

Reaktionsgleichung

[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH2:8]O.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]([CH2:8][CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][N:2]2[CH3:1])[CH2:29]1

Komponenten

Reaktionsbedingungen

Temperatur: 60 °C

Versuchsvorschrift

A cooled (0° C.) solution of 1-methylpiperidine-2-methanol (97 mg, 0.75 mmol) and diisopropylethylamine (0.31 mL, 1.75 mmol) in anhydrous acetonitrile (12 mL) under nitrogen was treated with methanesulfonyl chloride (86 mg, 0.75 mmol), stirred 3 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-((1-methylpiperidin-2-yl)methyl)pyrrolidine-3-carboxylic acid (121 mg, 55%) as a white foam. NMR (D2O) δ 3.60-4.00 (m, 4 H), 3.15-3.55 (m, 3 H), 2.90 (m, 2 H), 2.67 (s, 3 H), 2.50-2.80 (m, 2 H), 2.00-2.30 (m, 1 H), 1.45-1.95 (m, 5 H), 1.10-1.40 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 328.1; MS (m−H2O+1): 310.1.

Aufarbeitung

concentrationThe reaction mixture was concentrated
customisolated

Quellen und Nachweise

ORD-Eintrag: ord-461173daa4ca4dde85ad1f3f9ad0cc42
Quelldatensatz: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09233985B2

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