Isopropanol → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(7H-purin-6-yl)pyrrolidine-3-carboxylic acid

HRID 61369Notes

Reaction equation

C([NH:4][C@:5]1([C:22](NC(C)(C)C)=[O:23])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]2[O:17]C(C)(C)C(C)(C)[O:14]2)[CH2:8][NH:7][CH2:6]1)(=O)C.Cl[C:30]1[N:38]=[CH:37][N:36]=[C:35]2[C:31]=1[NH:32][CH:33]=[N:34]2.C(N(C(C)C)CC)(C)C.CC([OH:51])C>C(Cl)Cl>[NH2:4][C@:5]1([C:22]([OH:23])=[O:51])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([C:30]2[N:38]=[CH:37][N:36]=[C:35]3[C:31]=2[NH:32][CH:33]=[N:34]3)[CH2:6]1

Participants

Conditions

Temperature: 80 °C

Procedure

A stirred solution of (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) in anhydrous 2-propanol (5 mL) was treated with 6-chloropurine (92 mg, 0.6 mmol) and diisopropylethylamine (0.174 mL, 1.0 mmol), heated to 80° C. for 18 h, then diluted with methylene chloride (20 mL). The mixture was filtered through Celite® and the filtrate concentrated. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-4-(3-boronopropyl)-1-(7H-purin-6-yl)pyrrolidine-3-carboxylic acid (41 mg, 20%) as a pale amber solid. NMR (D2O) δ 8.20-8.45 (m, 2 H), 4.20-4.60 (m, 2 H), 3.50-4.00 (m, 2 H), 2.60-2.80 (m, 2 H), 1.65 (m, 1 H), 1.20-1.55 (m, 3 H), 0.65-0.75 (m, 2 H). MS (m+1): 335.2; MS (m−H2O+1): 317.1.

Workup

filtrationThe mixture was filtered through Celite®
concentrationthe filtrate concentrated
customisolated

Sources & evidence

ORD record: ord-58437a28662d478a88eead049ae8825d
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440995B2

Reaction notes

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