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

HRID 1959518

反応式

HRID 1959518 の反応式
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[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[CH2:27][CH2:28][CH2:29][N:30](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[CH:7]=[N:8][N:9]([C:12]2[CH:17]=[C:16]([C:18](=[O:20])[NH:30][CH:29]3[CH2:27][CH2:28]3)[CH:15]=[CH:14][C:13]=2[CH3:21])[C:10]=1[NH2:11])=[O:5])[CH3:2]

参加物

9

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 580890025-Amino-1-(5-carboxy-2-methyl-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester

生成物 1

HCID 114842585-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester収率 79%

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)-1H-pyrazole-4-carboxylic acid ethyl ester (47 mg, 0.16 mind, 1.0 eq), EDCI (62 mg, 0.32 mmol, 2.0 eq), HOBt (44 mg, 0.32 mmol, 2.0 eq), and diisopropylethyl amine (119 μL, 0.32 mmol, 2.0 eq) in DMF (5 mL) which had been stirred at RT for 15 min was added cyclopropylamine (23 μL, 0.32 mmol, 2.0 eq). After stirring overnight, the solution was diluted with EtOAc and water and the organic layer was washed with water and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography on silica gel eluted with 8/2 EtOAc/hexanes to provide the product as a colorless oil (42 mg, 79%). HPLC (4 minute 10-95 gradient) tR1.84 min; MS m/z 329.09 [M+H]+; 1H NMR (CD3OD), δ 7.96 (s, 1H, NH), 7.88 (d, J=7.9 Hz, 1H), 7.78 (s, 1H), 7.75 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 4.28 (q, J=7.1 Hz, 2H), 2.83 (m, 1H), 2.16 (s, 3H), 1.35 (d, J=7.0 Hz, 3H), 0.78 (dd, J=12.3, 7.0 Hz, 2H), 0.63 (dd, J=7.0, 4.5 Hz, 2H) ppm; 13C NMR (CD3OD), δ 170.1, 165.8, 152.3, 142.1, 141.8, 137.2, 134.6, 132.8, 130.0, 128.2, 128.1, 95.8, 60.8, 24.1, 17.6, 14.9, 6.6 ppm.

後処理

  1. washthe organic layer was washed with water and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude residue was purified by flash chromatography on silica gel
  5. washeluted with 8/2 EtOAc/hexanes

出典と根拠

ORDレコード
ord-e4c9479673d340a08ee372c31ff8a470
出典データセット
uspto-grants-2013_04
特許番号
US08410160B2

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