Diisopropylethylamine → 6-(cis-2-amino-3,3-difluorocyclohexylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 516067

Reaktionsgleichung

Reaktionsgleichung von HRID 516067
[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4](Cl)[N:3]=1.Cl.[F:26][C:27]1([F:35])[CH2:32][CH2:31][CH2:30][C@@H:29]([NH2:33])[C@H:28]1[NH2:34].CCN(C(C)C)C(C)C>C(#N)C>[NH2:34][C@H:28]1[C:27]([F:35])([F:26])[CH2:32][CH2:31][CH2:30][C@H:29]1[NH:33][C:4]1[N:3]=[C:2]([Cl:1])[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]=1[F:23]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 583175754,6-dichloro-2-[(2,4-dimethoxyphenyl)methyl]-7-fluoro-1H,2H,3H-pyrrolo[3,4-c]pyridin-3-oneHCID 67238749cis-3,3-Difluorocyclohexane-1,2-diamine hydrochloride

Produkt 1

HCID 866547266-(cis-2-amino-3,3-difluorocyclohexylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4,6-dichloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (100 mg, 0.269 mmol) and cis-3,3-difluorocyclohexane-1,2-diamine hydrochloride (75 mg, 0.404 mmol) and DIPEA (118 μL, 0.674 mmol) in acetonitrile (449 μL) was stirred at 100° C. for 3 d. The reaction mixture was concentrated to a brown oil and reconstituted in DMF (1 mL). The residue was purified by preparative HPLC, the appropriate fraction was collected, and excess acetonitrile was evaporated. The residue was treated with saturated aq sodium carbonate and extracted with EtOAc (3×20 mL). The organic layers were combined, dried over sodium sulfate, and concentrated to give the title compound as a colorless residue (13.7 mg, 10%). [M+H] calc'd for C22H24ClF3N4O3, 485; found, 485.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated to a brown oil
  2. customThe residue was purified by preparative HPLC
  3. customthe appropriate fraction was collected
  4. customexcess acetonitrile was evaporated
  5. additionThe residue was treated with saturated aq sodium carbonate
  6. extractionextracted with EtOAc (3×20 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-224cd388c5494fd8be4ceb28c4c2dc53
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108970B2

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