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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methyl-1h-pyrazole-4-carboxylic acid ethyl ester

HRID 1959520
ノート
印刷プレビュー

反応式

HRID 1959520 の反応式
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]([C:12]2[CH:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[CH:14][C:13]=2[CH3:21])[C:10]=1[NH2:11])=[O:5])[CH3:2].CCN=C=N[CH2:28][CH2:29][CH2:30][N:31](C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C1(N)CC1>CN(C=O)C.CCOC(C)=O.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]([C:12]2[CH:17]=[C:16]([C:18](=[O:20])[NH:31][CH:30]3[CH2:28][CH2:29]3)[CH:15]=[CH:14][C:13]=2[CH3:21])[C:10]=1[NH2:11])=[O:5])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 670242365-Amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

生成物 1

HCID 11221556
5-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methyl-1h-pyrazole-4-carboxylic acid ethyl ester
収率 17.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 5-amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (150 mg, 0.49 mmol, 1.0 eq), EDCI (190 mg, 0.98 mmol, 2.0 eq), HOBt (134 mg, 0.98 mmol, 2.0 eq), and diisopropylethyl amine (362 μL, 0.98 mmol, 2.0 eq) in DMF (5 mL) which had been stirred at RT for 15 min was added cyclopropylamine (68 μL, 0.98 mmol, 2.0 eq). After stirring overnight, the solution was diluted with EtOAc and water and the organic layer was washed with water (2×) and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography on silica gel (gradient elution, 3/2 EtOAc/hexanes then 100% EtOAc) to provide the product as a white solid (29 mg, 17%). HPLC (4 minute 10-95 gradient) tR1.97 min; MS m/z 343 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.1 Hz, 1H), 7.76 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 4.29 (q, J=7.0 Hz, 2H), 2.84 (m, 1H), 2.34 (s, 3H), 2.18 (s, 3H), 1.36 (t, J=7.0 Hz, 3H), 0.79 (d, J=5.5 Hz, 2H), 0.62 (s, 2H) ppm; 13C NMR (CD3OD), δ 168.1, 164.4, 151.3, 149.8, 140.1, 135.2, 132.6, 130.7, 127.9, 126.3, 92.0, 58.6, 22.1, 15.7, 12.9, 12.6, 4.6 ppm.

後処理

  1. washthe organic layer was washed with water (2×) and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude residue was purified by flash chromatography on silica gel (
  5. washgradient elution, 3/2 EtOAc/hexanes

出典と根拠

ORDレコード
ord-6b5a71d9c47740be8108d9e9301312d2
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08410160B2

反応ノート

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