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

HRID 884797

반응식

HRID 884797 반응식
[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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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) tR 1.84 min; MS m/z 329.09 [M+H]+; 1H NMR (CD3OD), δ 7.96 (s, 1 H, NH), 7.88 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.75 (s, 1 H), 7.50 (d, J=8.0 Hz, 1 H), 4.28 (q, J=7.1 Hz, 2 H), 2.83 (m, 1 H), 2.16 (s, 3 H), 1.35 (d, J=7.0 Hz, 3 H), 0.78 (dd, J=12.3, 7.0 Hz, 2 H), 0.63 (dd, J=7.0, 4.5 Hz, 2 H) 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.

후처리

  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

출처 및 근거

ORD 기록
ord-2df266b6bd1d42609598c9e4d69e2778
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08242117B2

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