Ammonia → US11401286, Example 133

HRID 1508796Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1508796
C(O[C:4](=[O:34])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]2[CH:18]=[C:17]([C:19]3[N:20](C(OC(C)(C)C)=O)[CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]3[CH2:31][CH2:32][CH2:33][C:14]=23)=[CH:8][CH:7]=1)C.[NH3:35]>CO>[NH:20]1[CH:21]=[CH:22][CH:23]=[C:19]1[C:17]1[N:16]=[C:15]2[CH2:31][CH2:32][CH2:33][C:14]2=[C:13]([NH:12][C:9]2[CH:8]=[CH:7][C:6]([CH2:5][C:4]([NH2:35])=[O:34])=[CH:11][CH:10]=2)[CH:18]=1

Komponenten

4

Edukt 2

HCID 222AmmoniaHCID 90338568tert-butyl 2-(4-((4-(2-ethoxy-2-oxoethyl)phenyl)amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)-1H-pyrrole-1-carboxylate

Produkt 1

HCID 90338445US11401286, Example 133Ausbeute 38 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 20-mL vial was charged with tert-butyl 2-(4-((4-(2-ethoxy-2-oxoethyl)phenyl)amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)-1H-pyrrole-1-carboxylate (0.110 g, 0.24 mmol, 1.0) and methanol (3 mL). To this solution was added NH3 (6.8 mL, 7N in methanol, 476 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 65 h. After this time, the crude reaction solution was concentrated under reduced pressure. The residue was adsorbed onto silica then purified by chromatography on silica using dichloromethane/(90:10:0.25 dichloromethane/methanol/aq. NH4OH) (10:0 to 0:10) as eluent followed by preparative HPLC (water/acetonitrile with 0.05% TFA) to afford 2-(4-((2-(1H-pyrrol-2-yl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)acetamide (0.030 g, 38%) as a brown solid. MW=332.40. 1H NMR (DMSO-d6, 500 MHz) δ 11.16 (br s, 1H), 7.93 (br s, 1H), 7.42 (br s, 1H), 7.26-7.22 (m, 2H), 7.17-7.13 (m, 2H), 7.03 (s, 1H), 6.85 (s, 1H), 6.74-6.71 (m, 1H), 6.39 (s, 1H), 6.05-6.20 (m, 1H), 3.34 (s, 2H), 2.86 (t, J=7.5 Hz, 2H), 2.78 (t, J=7.5 Hz, 2H), 2.05 (quin, J=7.5 Hz, 2H). MS: ESI, m/z 333 [M+H]+. Treatment with 1.25M HCl in methanol afforded the title compound (0.035 g, 100%) as an off-white solid. MW=368.86. M.p. 163-165° C. 1H NMR (DMSO-d6, 500 MHz) δ 13.43 (br s, 1H), 12.06 (br s, 1H), 9.46 (br s, 1H), 7.52 (br s, 1H), 7.40-7.36 (m, 2H), 7.32-7.28 (m, 2H), 7.12-7.09 (m, 1H), 7.08 (s, 1H), 7.06-7.03 (m, 1H), 6.92 (br s, 1H), 6.29-6.25 (m, 1H), 3.43 (s, 2H), 3.11 (t, J=7.5 Hz, 2H), 2.87 (t, J=7.5 Hz, 2H), 2.20 (quin, J=7.5 Hz, 2H); APCI MS m/z 333 [M+H]+.

Aufarbeitung

  1. customThe vial was sealed
  2. customAfter this time, the crude reaction solution
  3. concentrationwas concentrated under reduced pressure
  4. customthen purified by chromatography on silica

Quellen und Nachweise

ORD-Eintrag
ord-455d4aed5e8f4fea8c8fe5ce48f7d091
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221843B2

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