Diisopropylethylamine → (1R,3S,5R)-2-[2-(3-Carbamoyl-indazol-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

HRID 1052131Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1052131
FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]([C@@H:18]1[CH2:23][C@@H:22]2[C@@H:20]([CH2:21]2)[NH:19]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:24]([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]([CH2:36][C:37](O)=[O:38])[N:28]=1)(=[O:26])[NH2:25].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.O>[CH2:8]([O:15][C:16]([C@@H:18]1[CH2:23][C@@H:22]2[C@@H:20]([CH2:21]2)[N:19]1[C:37](=[O:38])[CH2:36][N:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:27]([C:24](=[O:26])[NH2:25])=[N:28]1)=[O:17])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682833421386457-64-2HCID 68284347(1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester trifluoroacetate

Produkt 1

HCID 68283506(1R,3S,5R)-2-[2-(3-Carbamoyl-indazol-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester trifluoroacetate (3.9 g, 9.77 mmol), (3-carbamoyl-indazol-1-yl)-acetic acid (prepared as described in Part A, 2.26 g, 9.77 mmol), HBTU (5.56 g, 14.66 mmol) in CH2Cl2 (60 mL) was added DIPEA (5.12 mL, 29.3 mmol). The reaction mixture was stirred for 48 h at RT under a nitrogen atmosphere. The reaction mixture was poured into water and extracted with CH2Cl2 (×3). The combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10) to afford the title compound. Rf, TLC (EtOAc)=0.85; MS (UPLC): 436.3 [M+NH4]+, 463.2 [M+HCOO]−; tR (HPLC conditions b): 1.82 min.

Aufarbeitung

  1. extractionextracted with CH2Cl2 (×3)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10)

Quellen und Nachweise

ORD-Eintrag
ord-06b8cf95b7dd45bf91b3793eaa6d656c
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388199B2

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