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

HRID 645503ノート

反応式

HRID 645503 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-3f2d284be33542c78735400454d8edb2
出典データセット
uspto-grants-2010_04
特許番号
US07704996B2

反応ノート

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