Sodium Carbonate → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(pyridin-3-ylmethyl)pyrrolidine-3-carboxylic acid

HRID 61360

반응식

HRID 61360 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.S([O-])([O-])(=O)=O.[Na+].[Na+].[N:36]1[CH:41]=[CH:40][CH:39]=[C:38]([CH:42]=O)[CH:37]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:46])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl.C(O)(=O)C>[NH2:4][C@:5]1([C:22]([OH:23])=[O:46])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:42][C:38]2[CH:37]=[N:36][CH:41]=[CH:40][CH:39]=2)[CH2:6]1

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 103713-PyridinecarboxaldehydeHCID 24436Sodium SulfateHCID 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 57331393(3R,4S)-3-amino-4-(3-boronopropyl)-1-(pyridin-3-ylmethyl)pyrrolidine-3-carboxylic acid수율 84.5%

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 111,2-Dichloroethane용매

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) (175 mg, 0.443 mmol) in anhydrous 1,2-dichloroethane (5 mL) was treated with anhydrous sodium sulfate (1 g) and pyridine-3-carboxaldehyde (75 mg, 0.70 mmol), stirred for 2 h, then treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and glacial acetic acid (2 drops) and stirred for 20 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 saturated aqueous sodium chloride (20 mL each), dried (MgSO4), and 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-(pyridin-3-ylmethyl)pyrrolidine-3-carboxylic acid (115 mg, 68%) as a white semisolid. NMR (d6-DMSO) δ 8.90 (m, 1 H), 8.74 (m, 1 H), 8.00 (m, 1 H), 7.12 (m, 1 H), 4.55-4.85 (m, 2 H), 3.10-4.00 (m, 3 H), 2.70-3.00 (m, 1 H), 1.70 (m, 2 H), 0.90-1.50 (m, 3 H), 0.55-0.70 (m, 2 H). MS (m+1): 308.4; MS (m−H2O+1): 290.4.

후처리

  1. stirringstirred for 20 h
  2. stirringthe mixture stirred for a few minutes
  3. extractionextracted with ethyl acetate (30 mL
  4. washThe combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customisolated

출처 및 근거

ORD 기록
ord-40872348ebf24f8692a3674580d51cd8
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440995B2

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