Ammonia → 2-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetamide

HRID 1042152ノート

反応式

HRID 1042152 の反応式
[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH:19]=2)[NH:16][C:15]([C:27]2[S:28][CH:29]([CH2:32][C:33]([OH:35])=O)[CH2:30][N:31]=2)=[CH:14]3)=[CH:6][CH:5]=1.Cl.C[N:38](C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.N>CCCCCC.C(OCC)(=O)C.CO.O.CN(C)C=O>[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([O:20][CH:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[CH:19]=2)[NH:16][C:15]([C:27]2[S:28][CH:29]([CH2:32][C:33]([NH2:38])=[O:35])[CH2:30][N:31]=2)=[CH:14]3)=[CH:6][CH:5]=1

参加物

10

反応物 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66726112{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid

生成物 1

HCID 667261272-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetamide収率 45.1%

試薬・触媒・溶媒 5

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8058Hexane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

A mixture of {2-[5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (400 mg), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (308 mg), 1-hydroxybenzotriazole (135 mg), and N,N-dimethylformamide (15 mL) was stirred at 50° C. for 30 min. The reaction solution was cooled to room temperature, 10% aqueous ammonia solution (1.5 mL) was added, and the mixture was stirred at room temperature for 2.5 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to basic silica gel column chromatography (methanol:ethyl acetate:hexane=0:50:50 to 15:85:0, volume ratio) to give an orange oil. The obtained orange oil was purified by preparative HPLC to give the title compound (180 mg, yield 45%) as a white amorphous solid.

後処理

  1. temperatureThe reaction solution was cooled to room temperature
  2. stirringthe mixture was stirred at room temperature for 2.5 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained crude product
  9. customto give an orange oil
  10. customThe obtained orange oil was purified by preparative HPLC

出典と根拠

ORDレコード
ord-0536b808924d469ba2dfdc5b9b35d31e
出典データセット
uspto-grants-2013_10
特許番号
US08557805B2

反応ノート

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