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

HRID 61365

反応式

HRID 61365 の反応式
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[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:39]([CH:46]=O)=[CH:38][CH:37]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:50])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl.C(O)(=O)C>[NH2:4][C@:5]1([C:22]([OH:23])=[O:50])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:46][C:39]2[C:40]3[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=3)[N:36]=[CH:37][CH:38]=2)[CH2:6]1

参加物

8

反応物 5

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 780724-QuinolinecarboxaldehydeHCID 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

生成物 1

HCID 57331398(3R,4S)-3-amino-4-(3-boronopropyl)-1-(quinolin-4-ylmethyl)pyrrolidine-3-carboxylic acid収率 27.4%

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 111,2-Dichloroethane溶媒

実験手順

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 1,2-dichloroethane (5 mL) was treated with anhydrous sodium sulfate (1 g) and quinoline-4-carboxaldehyde (110 mg, 0.7 mmol), stirred for 2 h, then treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and glacial acetic acid (2 drops) and stirred for 16 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-(quinolin-4-ylmethyl)pyrrolidine-3-carboxylic acid (49 mg, 23%) as a pale amber solid. NMR (D2O) δ 9.12 (d, J=5.5 Hz, 1 H), 8.41 (d, J=8.5 Hz, 1 H), 8.23 (d, J=8.5 Hz, 1 H), 8.10-8.20 (m, 2 H), 8.00 (t, J=8.5 Hz, 1 H), 5.30 (m, 2 H), 4.06 (d, J=12.5 Hz, 1 H), 3.83 (m, 2 H), 3.51 (t, J=11.5 Hz, 1 H), 2.50-2.70 (m, 1 H), 1.60 (m, 1 H), 1.15-1.30 (m, 3 H), 0.60-0.70 (m, 2 H). MS (m−H2O+1): 340.3; MS (m−2H2O+1): 322.1.

後処理

  1. stirringstirred for 16 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

出典と根拠

ORDレコード
ord-52a85f3115cc40fcbd1334475b362c5d
出典データセット
uspto-grants-2016_09
特許番号
US09440995B2

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