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

HRID 61383

반응식

HRID 61383 반응식
[OH:1]CCN1CCCC1.[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:1])[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]2[CH2:9][CH2:11][CH2:14][CH2:13]2)[CH2:28]1

참가 물질

6

반응물 4

HCID 31297Methanesulfonyl chlorideHCID 762881-PyrrolidineethanolHCID 81531DiisopropylethylamineHCID 67516451(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

생성물 1

HCID 57331518(3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(pyrrolidin-1-yl)ethyl)pyrrolidine-3-carboxylic acid수율 81.1%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
60 °C

실험 절차

A cooled (0° C.) solution of N-(2-hydroxyethyl)pyrrolidine (92 mg, 0.80 mmol) and diisopropylethylamine (0.32 mL, 1.8 mmol) in anhydrous acetonitrile (12 mL) under nitrogen was treated with methanesulfonyl chloride (92 mg, 0.80 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-(2-(pyrrolidin-1-yl)ethyl)pyrrolidine-3-carboxylic acid (127 mg, 60%) as a white foam. NMR (D2O) δ 3.80-4.00 (m, 2 H), 3.50-3.80 (m, 4 H), 3.40 (t, J=11 Hz, 1 H), 3.05 (m, 2 H), 2.55-2.75 (m, 4 H), 2.05 (m, 2 H), 1.90 (m, 2 H), 1.60 (m, 1 H), 1.10-1.40 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 314.0; MS (m−H2O+1): 296.2.

후처리

  1. concentrationThe reaction mixture was concentrated
  2. customisolated

출처 및 근거

ORD 기록
ord-4aefc3f90e4c47b6aa76f252a78e2da4
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440995B2

연결된 노트

불러오는 중…