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

HRID 590724Notes

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−2H2O+1): 280.1.

Workup

concentrationThe reaction mixture was concentrated
customisolated

Sources & evidence

ORD record: ord-4058961eb09a45fba442a5260a84df76
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233985B2

Reaction notes

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