Acetic Acid → (3R,4S)-3-amino-1-(2-aminocyclopentyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

HRID 590705

반응식

HRID 590705 반응식
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.C([NH:36][CH:37]1[CH2:41][CH2:40][CH2:39][C:38]1=O)(OC(C)(C)C)=O.S([O-])([O-])(=O)=[O:44].[Na+].[Na+].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl>[NH2:4][C@:5]1([C:22]([OH:23])=[O:44])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH:38]2[CH2:39][CH2:40][CH2:41][CH:37]2[NH2:36])[CH2:6]1

참가 물질

8

반응물 6

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 357962tert-butyl N-(2-oxocyclopentyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 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 57331394(3R,4S)-3-amino-1-(2-aminocyclopentyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid수율 77.5%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

반응 조건

온도
40 °C

실험 절차

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) and 2-(N—BOC-amino)cyclopentane-1-one (0.199 g, 1.0 mmol) in anhydrous 1,2-dichloroethane (5 mL) was treated with anhydrous sodium sulfate (1 g) and glacial acetic acid (30 mg, 0.5 mmol), stirred at 40° C. for 1.5 h, then cooled to room temperature and treated with sodium triacetoxyborohydride (276 mg, 1.3 mmol) and stirred for 18 h. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and brine (20 mL each), dried (MgSO4), and concentrated in vacuo. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-aminocyclopentyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (116 mg, 57%) as a white powder. NMR (D2O) δ 3.85-4.05 (m, 4 H), 3.77 (d, J=12.5 Hz, 1 H), 3.42 (dt, J1=11.5 Hz, J2=4 Hz, 1 H), 2.50-2.65 (m, 1 H), 2.10-2.35 (m, 2 H), 1.75-1.95 (m, 4 H), 1.55-1.65 (m, 1 H), 1.15-1.40 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 300.0; MS (m−H2O+1): 281.9.

후처리

  1. temperaturecooled to room temperature
  2. stirringstirred for 18 h
  3. stirringthe mixture stirred for a few minutes
  4. extractionextracted with ethyl acetate (30 mL
  5. washThe combined organic solution was washed with water and brine (20 mL each)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customisolated

출처 및 근거

ORD 기록
ord-befc6d9a56c64b29a022acb19a868e6c
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233985B2

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