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1,2-Dichloroethane → Tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-(4-{[10-(pyridin-2-ylmethyl)-9,10-diazatricyclo[4.2.1.12,5]dec-9-yl]carbonyl}benzyl)pyrrolidine-1-carboxylate

HRID 1804653
ノート
印刷プレビュー

反応式

HRID 1804653 の反応式
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@H:13]([OH:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:11][CH2:10][C@H:9]1[CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1([C@H]([C@H]2CC[C@@H](CC3C=CC(C(N4CCC(C5N=CSC=5)CC4)=O)=CC=3)[NH:40]2)O)C=CC=CC=1.[CH:64]1[CH:69]=[N:68][C:67]2N(O)N=N[C:66]=2[CH:65]=1.[CH2:74](Cl)[CH2:75]Cl.C[CH2:79][N:80]([CH:84]([CH3:86])[CH3:85])[CH:81]([CH3:83])[CH3:82]>CN(C=O)C>[OH:20][C@H:13]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C@H:12]1[CH2:11][CH2:10][C@@H:9]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([N:40]3[CH:83]4[CH2:74][CH2:75][CH:85]3[CH:84]3[N:80]([CH2:79][C:67]5[CH:66]=[CH:65][CH:64]=[CH:69][N:68]=5)[CH:81]4[CH2:82][CH2:86]3)=[O:28])=[CH:29][CH:30]=2)[N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 50997280(R)-phenyl[(2R,5S)-5-(4-{[4-(1,3-thiazol-4-yl)-piperidin-1-yl]carbonyl}benzyl)pyrrolidine-2-yl]methanolHCID 670587074-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid

生成物 1

HCID 67986715
Tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-(4-{[10-(pyridin-2-ylmethyl)-9,10-diazatricyclo[4.2.1.12,5]dec-9-yl]carbonyl}benzyl)pyrrolidine-1-carboxylate
収率 42%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of 4-{((2s,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl)methyl}benzoic acid (50 mg, 0.13 mmol) and the title compound from Step B above (37 mg, 0.13 mmol) in 1.5 mL anhydrous DMF was added a 0.5 M solution of HOAt in DMF (0.24 mL, 0.13 mmol) followed by EDC (46 mg, 0.26 mmol) and DIEA (17 μL, 0.13 mmol). The resulting mixture was stirred at RT under nitrogen atmosphere for 16 h. The mixture was washed with water and extracted with dichloromethane (2×5 mL). The organics were combined, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was purified by preparative TLC plate (1000 uM) eluting with 5% MeOH in dichloromethane to afforded the product (32 mg, 42%). ESI-MS calculated for C38H46N4O4: Exact Mass: 622.35. Found 623.38 (MH)+ and 645.33 (MNa)+.

後処理

  1. washThe mixture was washed with water
  2. extractionextracted with dichloromethane (2×5 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified by preparative TLC plate (1000 uM)
  7. washeluting with 5% MeOH in dichloromethane

出典と根拠

ORDレコード
ord-9238bad517944318bc5e049652450a52
出典データセット
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08354403B2

反応ノート

読み込み中…

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