Sodium Acetate → 5-(4-chlorophenyl)-5-(3-{4-[1-(3,3-difluoropyrrolidin-1-yl)ethyl]piperidin-1-yl}-3-oxopropyl)-5H-imidazo[2,1-a]isoindole

HRID 46174ノート

反応式

HRID 46174 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:20][CH2:21][C:22]([N:24]3[CH2:29][CH2:28][CH:27]([C:30](=O)[CH3:31])[CH2:26][CH2:25]3)=[O:23])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3=[N:17][CH:18]=[CH:19][N:9]23)=[CH:4][CH:3]=1.[Cl-].[F:34][C:35]1([F:40])[CH2:39][CH2:38][NH2+:37][CH2:36]1.CC([O-])=O.[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CC(O)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:20][CH2:21][C:22]([N:24]3[CH2:25][CH2:26][CH:27]([CH:30]([N:37]4[CH2:38][CH2:39][C:35]([F:40])([F:34])[CH2:36]4)[CH3:31])[CH2:28][CH2:29]3)=[O:23])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3=[N:17][CH:18]=[CH:19][N:9]23)=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 517045Sodium AcetateHCID 27828263,3-Difluoropyrrolidine, chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 58415640HCID 58415640、化合物

生成物 1

HCID 566664195-(4-chlorophenyl)-5-(3-{4-[1-(3,3-difluoropyrrolidin-1-yl)ethyl]piperidin-1-yl}-3-oxopropyl)-5H-imidazo[2,1-a]isoindole

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 6344Dichloromethane溶媒

実験手順

To a mixture of 1-(1-{3-[5-(4-chlorophenyl)-5H-imidazo[2,1-a]isoindol-5-yl]propanoyl}piperidin-4-yl)ethanone (27 mg), 3,3-difluoropyrrolidinium chloride (17 mg) and NaOAc (15 mg) in CH2Cl2 was added AcOH (0.01 mL). After stirring the resulting mixture for 30 minutes NaBH(OAc)3 (26 mg) was added and allowed to stir overnight. The reaction mixture was then partitioned between saturated aqueous NaHCO3 and CH2Cl2. Aqueous layer was extracted with CH2Cl2 (2×). Combined organic layers were dried over Na2SO4 and concentrated. Purification by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-95% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min) afforded title compound as a white solid. HRMS. Found, 539.2387; calcd for (M+H)+, 539.2384. 1H NMR (500 MHz, CDCl3): δ 7.86 (d, J=7.62 Hz, 1 H); 7.43-7.38 (m, 1 H); 7.35-7.26 (m, 4 H); 7.25-7.19 (m, 1 H); 7.11 (d, J=8.36 Hz, 2 H); 6.96 (d, J=9.03 Hz, 1 H); 4.54 (d, J=13.34 Hz, 1 H); 3.31 (d, J=13.41 Hz, 1 H); 3.11-3.03 (m, 1 H); 2.91-2.80 (m, 3 H); 2.76-2.61 (m, 3 H); 2.38-2.13 (m, 4 H); 1.69-1.50 (m, 6 H); 0.90-0.83 (m, 4 H).

後処理

  1. additionwas added
  2. customThe reaction mixture was then partitioned between saturated aqueous NaHCO3 and CH2Cl2
  3. extractionAqueous layer was extracted with CH2Cl2 (2×)
  4. dry with materialCombined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-95% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min)

出典と根拠

ORDレコード
ord-cf58ac05f7324b8b80f17e90c1c31663
出典データセット
uspto-grants-2013_09
特許番号
US08541595B2

反応ノート

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