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

HRID 860714노트

반응식

HRID 860714 반응식
[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

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2회HCID 16072613methyl 13-cyclohexyl-6,7-dihydro-6-(morpholinylcarbonyl)-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
90 °C

실험 절차

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, 1 H), 1.40–1.55 (m, 2 H), 1.60–1.68 (m, 1 H), 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).

후처리

  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®

출처 및 근거

ORD 기록
ord-8b2153132f9c42b9ab4bf884fce1890f
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07153848B2

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