Isobutanol → Isobutyl 1-(8-methoxy-5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxylate

HRID 710939

反応式

HRID 710939 の反応式
[CH3:1][O:2][C:3]1[C:4]2[N:5]([N:19]=[C:20]([C:22]3([C:25]([OH:27])=[O:26])[CH2:24][CH2:23]3)[N:21]=2)[C:6]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[O:13][CH2:12]3)=[CH:7][CH:8]=1.[CH2:28](O)[CH:29]([CH3:31])[CH3:30].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:28][CH:29]([CH3:31])[CH2:30][O:26][C:25]([C:22]1([C:20]2[N:21]=[C:4]3[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[C:6]([C:9]4[CH:10]=[C:11]5[C:15](=[CH:16][CH:17]=4)[C:14](=[O:18])[O:13][CH2:12]5)[N:5]3[N:19]=2)[CH2:23][CH2:24]1)=[O:27]

参加物

6

反応物 3

HCID 6560IsobutanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 686549441-[5-(1,3-dihydro-1-oxo-5-isobenzofuranyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridin-2-yl]Cyclopropanecarboxylic acid

生成物 1

HCID 71611998Isobutyl 1-(8-methoxy-5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxylate収率 62%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
50 °C

実験手順

A mixture of 1-[8-methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxylic acid (250 mg, 685 μmol), isobutanol (100 μL, 1.37 mmol), DMAP (250 mg, 2.05 mmol) and EDCI.HCl (262 mg, 1.37 mmol) in DCM (14 mL) was stirred at 50° C. for 2 hours in a sealed vial, before it was diluted with DCM (80 mL), washed with an aqueous 1 M solution of HCl (40 mL) and evaporated to dryness. The crude mixture was redissolved in MeCN (˜2 mL) and the crude product was crystallized upon addition of water (˜2 mL). Column chromatography (gradient EtOAc 20 to 100% in pet. ether) and subsequent recrystallization in MeCN and water afforded the title compound as colorless crystals (178 mg, 62%). HPLC-Retention time (XE Metode 7 CM): 2.34 minutes. Detected “M+1”-mass: 422.16. Calculated “M+1”-mass: 422.17. 1H NMR (DMSO, 600 MHz): δ=8.22 (br s, 1H), 8.13 (dd, 1H, J=8.1 Hz, 1.5 Hz), 8.00 (d, 1H, J=8.0 Hz), 7.40 (d, 1H, J=8.2 Hz), 7.24 (d, 1H, J=8.2 Hz), 5.51 (s, 2H), 4.04 (s, 3H), 3.84 (d, 2H, J=6.5 Hz), 1.79 (m, 1H), 1.61-1.54 (m, 2H), 1.54-1.46 (m, 2H), 0.78 (d, 6H, J=6.7 Hz) ppm.

後処理

  1. washwashed with an aqueous 1 M solution of HCl (40 mL)
  2. customevaporated to dryness
  3. dissolutionThe crude mixture was redissolved in MeCN (˜2 mL)
  4. customthe crude product was crystallized upon addition of water (˜2 mL)
  5. customColumn chromatography (gradient EtOAc 20 to 100% in pet. ether) and subsequent recrystallization in MeCN

出典と根拠

ORDレコード
ord-36cf8df63a22401292bc8c096b3c5afb
出典データセット
uspto-grants-2015_11
特許番号
US09181248B2

関連ノート

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