Water → Dehydroaripiprazole

HRID 43237노트

반응식

HRID 43237 반응식
[CH:1]1[CH:2]=[C:3]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]4[CH2:30][CH2:29][C:27](=[O:28])[NH:26][C:24]=4[CH:25]=3)[CH2:11][CH2:10]2)[C:4]([Cl:8])=[C:5]([Cl:7])[CH:6]=1.FC(F)(F)C(O)=O.O.[OH-].[Na+]>O1CCCC1>[CH2:11]1[N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]3[CH:30]=[CH:29][C:27]([NH:26][C:24]=3[CH:25]=2)=[O:28])[CH2:13][CH2:14][N:9]([C:3]2[CH:2]=[CH:1][CH:6]=[C:5]([Cl:7])[C:4]=2[Cl:8])[CH2:10]1

참가 물질

6

반응물 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 60795Aripiprazole

생성물 1

HCID 10114519Dehydroaripiprazole수율 102.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Aripiprazole (Formula VIA; 15 g, 0.03 mol) was dissolved in anhydrous tetrahydrofuran (360 mL). Trifluoroacetic acid (12 mL, 0.16 mol) was added to the clear solution. 1,2-Dichloro-4,5-dicyano quinone (24.3 g, 0.11 mol) was added and the mixture was stirred at room temperature under nitrogen atmosphere. The reaction was stirred for 40 minutes and TLC showed no starting material remaining Water (1.5 L) was added then reaction mixture basified with 50% aq NaOH until pH 12. The reaction mixture was extracted with dichloromethane (3×1 L) and the combined organics were dried (MgSO4) to give the crude product. This was purified by column chromatography on silica eluting with dichloromethane to 10% methanol/dichloromethane. The product was further purified by recrystallisation from 2-propanol to give the desired product (13.7 g, 92%) as an off white solid. 1H-NMR (400 MHz, CDCl3) δ 12.33 (1H, br s), 7.72 (1H, d), 7.42 (1H, d), 7.16-7.11 (2H, m), 6.98-6.93 (1H, dd), 6.83-6.79 (2H, m), 6.53 (1H, d), 4.10 (2H, t), 3.09 (4H, br s), 2.67 (4H, br s), 2.52 (2H, t), 1.93-1.70 (4H, m). LCMS (acidic method) [M+H]+ 446.02, rt 14.246 min.

후처리

  1. stirringThe reaction was stirred for 40 minutes
  2. additionwas added
  3. customreaction mixture
  4. extractionThe reaction mixture was extracted with dichloromethane (3×1 L)
  5. dry with materialthe combined organics were dried (MgSO4)
  6. customto give the crude product
  7. customThis was purified by column chromatography on silica eluting with dichloromethane to 10% methanol/dichloromethane
  8. customThe product was further purified by recrystallisation from 2-propanol

출처 및 근거

ORD 기록
ord-afcb54bcb171469d92f46f5b1b8abf8c
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536328B2

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