Diisopropylethylamine → tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

HRID 711589Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 711589
[Cl:1][C:2]1[C:7]2[C:8](=[O:18])[N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:6]=2[C:5]([F:19])=[C:4](Cl)[N:3]=1.[NH2:21][C@@H:22]1[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].C(N(C(C)C)CC)(C)C>CS(C)=O.CC(O)C>[C:31]([O:30][C:29]([NH:28][C@@H:23]1[C@H:22]([NH:21][C:4]2[N:3]=[C:2]([Cl:1])[C:7]3[C:8](=[O:18])[N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:6]=3[C:5]=2[F:19])[CH2:27][CH2:26][O:25][CH2:24]1)=[O:35])([CH3:34])([CH3:32])[CH3:33]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamateHCID 86654739tert-Butyl 4,6-dichloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Produkt 1

HCID 86654748tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylateAusbeute 26,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of tert-butyl 4,6-dichloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (1.24 g, 3.85 mmol), tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (1.00 g, 4.62 mmol), diisopropylethylamine (3.36 mL, 19.27 mmol) in DMSO (10 mL) and 2-propanol (40 mL) were heated to 100° C. in an oil bath for 20 h. The reaction was repeated on the same scale and both reaction solutions were combined and concentrated. The mixture was purified via silica gel flash chromatography eluting with EtOAc and hexanes (10-50% EtOAc gradient) to give the title compound as a pale pinkish-white solid (510 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36 (s, 9H), 1.50 (s, 3H), 1.59-1.61 (m, 1H), 1.97-1.99 (m, 1H), 1.97-1.99 (m, 1H), 3.46-3.49 (m, 2H), 3.80-3.83 (m, 3H), 4.31-4.33 (m, 1H), 4.73 (s, 1H), 6.59 (d, J=7.30 Hz, 1H), 7.43 (d, J=7.30 Hz, 1H). [M+H] calc'd for C22H30ClFN4O6, 501. found, 501.

Aufarbeitung

  1. concentrationconcentrated
  2. customThe mixture was purified via silica gel flash chromatography
  3. washeluting with EtOAc and hexanes (10-50% EtOAc gradient)

Quellen und Nachweise

ORD-Eintrag
ord-51a5927a1adb4f3b8cf196de2c8dba15
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181255B2

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