Hydrochloric Acid → 13-cyclohexyl-6-(morpholine-4-carbonyl)-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

HRID 1394846Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1394846
[OH-].[Na+].[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:35]([O:37]C)=[O:36])=[CH:14][C:15]=3[N:16]3[CH2:22][CH:21]([C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:24])[CH2:20][C:19]4[CH:31]=[CH:32][CH:33]=[CH:34][C:18]=4[C:17]=23)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Cl>CO.O1CCCC1>[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:35]([OH:37])=[O:36])=[CH:14][C:15]=3[N:16]3[CH2:22][CH:21]([C:23]([N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)=[O:24])[CH2:20][C:19]4[CH:31]=[CH:32][CH:33]=[CH:34][C:18]=4[C:17]=23)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 16072613methyl 13-cyclohexyl-6,7-dihydro-6-(morpholinylcarbonyl)-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

Produkt 1

HCID 1149652413-cyclohexyl-6-(morpholine-4-carbonyl)-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acidAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Sodium hydroxide (200 μL, 0.2 mmol) was added to a solution of the preceding methyl ester (60 mg, 0.127 mmol) in methanol (1.2 mL) and tetrahydrofuran (1.2 mL) in a microwave vial. The vial was sealed and the contents heated at 90° C. for 10 min in a microwave apparatus, at which time the vial was cooled and additional NaOH was added (200 μL, 0.2 mmol). The solution was heated for another 5 min at 90° C. when LC/MS showed complete hydrolysis of the ester. The solution was acidified with dilute hydrochloric acid to precipitate the crude acid. The solid was collected and purified on the Shimadzu preparative liquid chromatograph. The product containing fraction was concentrated on a Speed Vac® to leave the titled compound as a colorless solid (50 mg, 83%). ESI-MS m/z 473 (MH+), 1H NMR (500 MHz, CD3OD) δ 1.24-1.35 (m, 1H), 1.40-1.55 (m, 2H), 1.60-1.68 (m, 1H), 1.77-2.22 (m, 6 H), 2.76 (m, 1 H), 2.88-3.04 (m, 1 H), 3.44-3.51 (m, 1 H), 3.58-3.93 (m, 9 H), 4.47-4.59 (m, 1 H), 4.89 (m, 1 H), 7.31-7.43 (m, 1 H), 7.47 (m, 3 H), 7.72 (m, 1 H), 7.88 (m, 1 H), 8.16 (m, 1 H).

Aufarbeitung

  1. customThe vial was sealed
  2. temperaturewas cooled
  3. temperatureThe solution was heated for another 5 min at 90° C. when LC/MS
  4. customto precipitate the crude acid
  5. customThe solid was collected
  6. custompurified on the Shimadzu preparative liquid chromatograph
  7. additionThe product containing fraction
  8. concentrationwas concentrated on a Speed Vac®

Quellen und Nachweise

ORD-Eintrag
ord-a3a93c5260fa44889eaf3adcb2ba543b
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07348425B2

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