1,2-Dichloroethane → Tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-(4-{[5-(1H-pyrazol-1-yl)piperidin-1-yl]carbonyl}benzyl)pyrrolidine-1-carboxylate

HRID 1804645

Reaktionsgleichung

Reaktionsgleichung von HRID 1804645
[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](O)=[O:27])=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:31]1([CH:36]2[CH2:41][CH2:40]NC[CH2:37]2)[CH:35]=[CH:34][CH:33]=[N:32]1.C1C=[N:46][C:45]2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>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:30]=[CH:29][C:25]([C:26]([N:46]3[CH2:37][CH:36]([N:31]4[CH:35]=[CH:34][CH:33]=[N:32]4)[CH2:41][CH2:40][CH2:45]3)=[O:27])=[CH:24][CH:23]=2)[N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 211930454-(1H-Pyrazol-1-yl)piperidineHCID 670587074-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid

Produkt 1

HCID 86666754Tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-(4-{[5-(1H-pyrazol-1-yl)piperidin-1-yl]carbonyl}benzyl)pyrrolidine-1-carboxylateAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of 4-{((2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl)methyl}benzoic acid (82 mg, 0.2 mmol) and 4-(1H-pyrazol-1-yl)piperidine (30 mg, 0.2 mmol) in 1.5 mL anhydrous DMF was added a 0.5 M solution of HOAt in DMF (0.4 mL, 0.2 mmol) followed by EDC (78 mg, 0.4 mmol) and DIEA (70 μL, 0.4 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 afford the title compound (88 mg, 81%). ESI-MS calculated for C32H40N4O4: Exact Mass: 544.30. Found 545.30 (MH)4 and 567.28 (MNa)+,

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-7c0b9da5d7e54e52b1548a49c1349770
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354403B2

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