Isopropyl iodide → 2-Cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxylic acid (4-benzyl-1-isopropylpiperidin-4-yl)amide

HRID 645503노트

반응식

HRID 645503 반응식
C(OC([N:8]1[CH2:13][CH2:12][C:11]([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([NH:14][C:15]([C:17]2[C:18]([NH:25][CH2:26][CH:27]3[CH2:34][CH2:33][C:30]4([CH2:32][CH2:31]4)[CH2:29][CH2:28]3)=[N:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=2)=[O:16])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+].[CH:55](I)([CH3:57])[CH3:56]>C(Cl)Cl.CCOC(C)=O>[CH2:35]([C:11]1([NH:14][C:15]([C:17]2[C:18]([NH:25][CH2:26][CH:27]3[CH2:34][CH2:33][C:30]4([CH2:31][CH2:32]4)[CH2:29][CH2:28]3)=[N:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=2)=[O:16])[CH2:12][CH2:13][N:8]([CH:55]([CH3:57])[CH3:56])[CH2:9][CH2:10]1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

참가 물질

7

반응물 4

HCID 6362Isopropyl iodideHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 687064324-Benzyl-4-({2-cyano-4-[(spiro[2.5]oct-6-ylmethyl)-amino]-pyrimidine-5-carbonyl}amino)piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 866277952-Cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxylic acid (4-benzyl-1-isopropylpiperidin-4-yl)amide

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4-benzyl-4-({2-cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]-pyrimidine-5-carbonyl}amino)piperidine-1-carboxylic acid tert-butyl ester (0.14 mmol) in CH2Cl2 (1.5 mL) is added TFA (0.4 mL) at 0° C. After stirring at room temperature for 0.5 h, the reaction mixture is concentrated in vacuo. The residue is dissolved in DMF (1.5 mL) and treated with K2CO3 (0.35 mmol) and isopropyl iodide (0.28 mmol) at 0° C. After stirring at room temperature for 5 h, the reaction mixture is diluted with AcOEt and washed with H2O and brine. The organic layer is dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified by RP-HPLC to give the title compound; 1H NMR (CDCl3), δ: 0.18-0.26 (2H, m), 0.27-0.34 (2H, m), 0.91-0.99 (2H, m), 1.01-1.13 (6H, s), 1.17-1.33 (2H, m), 1.63-1.97 (7H, m), 2.15-2.40 (4H, m), 2.64-2.90 (3H, m), 3.15 (2H, s), 3.46 (2H, dd), 5.28 (1H, s), 7.02-7.10 (2H, m), 7.20-7.30 (3H, m), 8.05 (1H, s), 8.70 (1H, bs).

후처리

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. dissolutionThe residue is dissolved in DMF (1.5 mL)
  3. stirringAfter stirring at room temperature for 5 h
  4. washwashed with H2O and brine
  5. dry with materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by RP-HPLC

출처 및 근거

ORD 기록
ord-3f2d284be33542c78735400454d8edb2
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07704996B2

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