Ethanol → 5-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-(2-hydroxy-ethoxy)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 884800

反応式

HRID 884800 の反応式
C(O[C:4](=[O:13])[C:5]([C:11]#[N:12])=[C:6]1[O:10][CH2:9][CH2:8][O:7]1)C.NC1[N:19]([C:20]2[CH:21]=[C:22]([CH:29]=[CH:30][C:31]=2[CH3:32])[C:23]([NH:25][CH:26]2[CH2:28][CH2:27]2)=[O:24])[N:18]=CC=1C(=O)C1C=CC=C(I)C=1.C(N(CC)CC)C.[CH2:49]([OH:51])[CH3:50]>>[CH2:49]([O:51][C:4]([C:5]1[C:6]([O:10][CH2:9][CH2:8][OH:7])=[N:18][N:19]([C:20]2[CH:21]=[C:22]([C:23](=[O:24])[NH:25][CH:26]3[CH2:28][CH2:27]3)[CH:29]=[CH:30][C:31]=2[CH3:32])[C:11]=1[NH2:12])=[O:13])[CH3:50]

参加物

5

反応物 4

HCID 702EthanolHCID 8471TriethylamineHCID 2766691Ethyl cyano(1,3-dioxolan-2-ylidene)acetateHCID 111676593-(5-amino-4-(3-iodobenzoyl)-1H-pyrazol-1-yl)-N-cyclopropyl-4-methylbenzamide

生成物 1

HCID 248607185-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-(2-hydroxy-ethoxy)-1H-pyrazole-4-carboxylic acid ethyl ester収率 62%

実験手順

A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6 C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS ink 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm.

後処理

  1. concentrationthe mixture was concentrated
  2. customthe residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

出典と根拠

ORDレコード
ord-d4428989362941a5a80622ba0ee3ac2d
出典データセット
uspto-grants-2012_08
特許番号
US08242117B2

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