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

HRID 590728ノート

反応式

HRID 590728 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.C([N:36]1[CH:45]([CH:46]=O)[CH2:44][CH:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH2:42]2)[CH2:37]1)(OC(C)(C)C)=O.S([O-])([O-])(=O)=[O:49].[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:49])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:46][C@@H:45]2[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:37][NH:36]2)[CH2:6]1

参加物

8

反応物 6

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 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-carboxamideHCID 86665785HCID 86665785、化合物

生成物 1

HCID 67517045(3R,4S)-3-amino-4-(3-boronopropyl)-1-(((S)-1,2,3,4-tetrahydroisoquinolin-3-yl)methyl)pyrrolidine-3-carboxylic acid収率 80.8%

試薬・触媒・溶媒 1

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) and N—BOC-tetrahydroisoquinoline-3-carboxaldehyde (0.196 g, 0.75 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 room temperature for 3 h, then cooled to room temperature and treated with sodium triacetoxyborohydride (212 mg, 1.0 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-4-(3-boronopropyl)-1-(((S)-1,2,3,4-tetrahydroisoquinolin-3-yl)methyl)pyrrolidine-3-carboxylic acid (146 mg, 62%) as a white solid. NMR (D2O) δ 7.10-7.30 (m, 4 H), 4.39 (br s, 2 H), 3.85-4.10 (m, 3 H), 3.60-3.80 (m, 3 H), 3.20-3.50 (m, 2 H), 2.90-3.10 (m, 1 H), 2.62 (m, 1 H), 1.60 (m, 1 H), 1.15-1.30 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 362.4; MS (m−H2O+1): 344.0.

後処理

  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

出典と根拠

ORDレコード
ord-028677f74bf2466d8927de48560c3c91
出典データセット
uspto-grants-2016_01
特許番号
US09233985B2

反応ノート

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