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

HRID 61380

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

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.

Workup

concentrationThe reaction mixture was concentrated
customisolated

Sources & evidence

ORD record: ord-3802a3036e4f4e3da033322a29b8350f
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440995B2

Linked notes

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