Diisopropylethylamine → (1R,3S,5R)-2-[2-(3-Acetyl-pyrazolo[3,4-c]pyridin-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

HRID 1052127Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1052127
Cl.[CH2:2]([O:9][C:10]([C@@H:12]1[CH2:17][C@@H:16]2[C@@H:14]([CH2:15]2)[NH:13]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:18]([C:21]1[C:29]2[C:24](=[CH:25][N:26]=[CH:27][CH:28]=2)[N:23]([CH2:30][C:31](O)=[O:32])[N:22]=1)(=[O:20])[CH3:19].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>CN(C=O)C>[CH2:2]([O:9][C:10]([C@@H:12]1[CH2:17][C@@H:16]2[C@@H:14]([CH2:15]2)[N:13]1[C:31](=[O:32])[CH2:30][N:23]1[C:24]2=[CH:25][N:26]=[CH:27][CH:28]=[C:29]2[C:21]([C:18](=[O:20])[CH3:19])=[N:22]1)=[O:11])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682838632-(3-Acetylpyrazolo[5,4-c]pyridin-1-yl)acetic acidHCID 90020119(1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester hydrochloride

Produkt 1

HCID 90019996(1R,3S,5R)-2-[2-(3-Acetyl-pyrazolo[3,4-c]pyridin-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester hydrochloride (2.98 g, 9.06 mmol), (3-acetyl-pyrazolo[3,4-c]pyridin-1-yl)-acetic acid (prepared as described in Part A, 3.2 g, 9.06 mmol) and HBTU (5.15 g, 13.59 mmol) in DMF (30.2 mL) was added DIPEA (4.75 mL, 27.2 mmol). The reaction mixture was stirred for 16 h at RT under a nitrogen atmosphere. DMF was evaporated. The residue was diluted in EtOAc and washed with aq. HCl 1N then with NaHCO3 (5% in water). The organic layer was dried (Phase separator) and concentrated. The residual oil was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10) to give the title compound. TLC, Rf (EtOAc)=0.33; MS (UPLC-MS): 419 [M+H]+; tR (HPLC conditions d): 2.97 min.

Aufarbeitung

  1. customDMF was evaporated
  2. additionThe residue was diluted in EtOAc
  3. washwashed with aq. HCl 1N
  4. customThe organic layer was dried (Phase separator)
  5. concentrationconcentrated
  6. customThe residual oil was purified by flash column chromatography on silica gel (c-hexane/EtOAc 10:0 to 0:10)

Quellen und Nachweise

ORD-Eintrag
ord-248f956998c5435fb01edd4ffe1bbe3a
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388199B2

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