Isoniazid → N-cyclopentyl-2-naphthalen-1-yl-N-[2-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)ethyl]acetamide

HRID 1925193ノート

反応式

HRID 1925193 の反応式
[C:1]([CH2:3][CH2:4][NH:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1)#[N:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:35]1([CH2:45][C:46]([OH:48])=O)[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[CH:37][CH:36]=1.C(N(C(C)C)CC)(C)C.[Li+].[Cl-].[C:60]([NH:68][NH2:69])(=O)[C:61]1[CH:66]=[CH:65][N:64]=[CH:63][CH:62]=1.C[O-].[Na+]>CN(C=O)C.C(O)C>[CH:6]1([N:5]([CH2:4][CH2:3][C:1]2[NH:69][N:68]=[C:60]([C:61]3[CH:66]=[CH:65][N:64]=[CH:63][CH:62]=3)[N:2]=2)[C:46](=[O:48])[CH2:45][C:35]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH:38]=[CH:37][CH:36]=2)[CH2:10][CH2:9][CH2:8][CH2:7]1

参加物

10

反応物 7

HCID 3767IsoniazidHCID 68621-Naphthaleneacetic AcidHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 27580023-(Cyclopentylamino)propionitrileHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942334Sodium Methoxide

生成物 1

HCID 67521944N-cyclopentyl-2-naphthalen-1-yl-N-[2-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)ethyl]acetamide

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

A DMF (5 mL) solution of N-(2-cyanoethyl)cyclopentylamine (4.7 mL, 32. mmol) was added to a stirred solution of HATU (15.3 g, 40.3 mmol), 1-naphthylacetic acid (5.0 g, 27 mmol), and diisopropylethylamine (7.0 mL, 40 mmol) in DMF (40 mL). The mixture stirred at room temperature overnight. Aqueous LiCl (5%) was added and the mixture was extracted three times with ethyl acetate (100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was carried to next step without further purification. A sample of this product (3.35 g, 11.0 mmol), isonicotinic hydrazide (1.0 g, 7.3 mmol) and sodium methoxide (600 mg, 11 mmol) was transferred to a pressure tube. Ethanol (4 mL) was added and the reaction was stirred at 120° C. overnight. The reaction was monitored by LCMS. Upon completion, the ethanol was removed in vacuo to afford the product as a solid. The crude mixture was separated by preparative HPLC and lyophilized to afford a solid. 1H NMR (400 MHz, d6-DMSO): δ 8.8 (m, 2H), 8.2 (m, 2H), 8.0-7.85 (m, 2H), 7.8-7.7 (m, 1H), 7.6-7.3 (m, 4H), 4.5-4.3 (m, 2H), 3.5 (t, 2H), 3.3-3.0 (m, 2H), 1.8-1.3 (m, 9H). MS (EI) for C26H27N5O: 426 (MH+).

後処理

  1. extractionthe mixture was extracted three times with ethyl acetate (100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was carried to next step without further purification
  7. stirringthe reaction was stirred at 120° C. overnight
  8. customUpon completion, the ethanol was removed in vacuo

出典と根拠

ORDレコード
ord-6b286b39465e4350acf1098b96f1a600
出典データセット
uspto-grants-2012_05
特許番号
US08178570B2

反応ノート

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