1-Hydroxybenzotriazole → 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}-N-methylacetamide

HRID 1042153ノート

反応式

HRID 1042153 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.[CH3:37][N:38](C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.CN>CCCCCC.C(OCC)(=O)C.CO.O.CN(C)C=O.C(N(CC)CC)C>[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]([NH:38][CH3:37])=[O:35])[CH2:30][N:31]=2)=[CH:14]3)=[CH:6][CH:5]=1

参加物

11

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 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 667259322-{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}-N-methylacetamide収率 49%

試薬・触媒・溶媒 6

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8058Hexane溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

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 (300 mg), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (231 mg), 1-hydroxybenzotriazole (162 mg), methylamine hydrochloride (81 mg), triethylamine (0.2 mL), and N,N-dimethylformamide (15 mL) was stirred at room temperature for 2 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 10:90:0, volume ratio) to give an orange oil. The obtained orange oil was purified by preparative HPLC to give the title compound (150 mg, yield 49%) as a white amorphous solid.

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude product
  7. customto give an orange oil
  8. customThe obtained orange oil was purified by preparative HPLC

出典と根拠

ORDレコード
ord-c6f2b21354334e5bb2573cca83509aab
出典データセット
uspto-grants-2013_10
特許番号
US08557805B2

反応ノート

読み込み中…