Water → 5-(2-(3-(2-(4-Hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide

HRID 2215503ノート

反応式

HRID 2215503 の反応式
Cl.[OH:2][C:3]1([CH3:9])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:17][NH:18][C:19]([N:21]1[C:29]2[C:24](=[CH:25][C:26]([O:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]([NH:40][CH2:41][C:42](O)=[O:43])=[O:39])[CH:32]=3)=[CH:27][CH:28]=2)[CH:23]=[CH:22]1)=[O:20].O>CN(C)C=O.C(OCC)(=O)C.O1CCCC1>[CH3:17][NH:18][C:19]([N:21]1[C:29]2[C:24](=[CH:25][C:26]([O:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]([NH:40][CH2:41][C:42]([N:6]4[CH2:7][CH2:8][C:3]([OH:2])([CH3:9])[CH2:4][CH2:5]4)=[O:43])=[O:39])[CH:32]=3)=[CH:27][CH:28]=2)[CH:23]=[CH:22]1)=[O:20]

参加物

7

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 21949209((4-(1-methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acidHCID 219492954-Methylpiperidin-4-ol hydrochloride

生成物 1

HCID 104802985-(2-(3-(2-(4-Hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide収率 75.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 21939870Tetrahydrofuran ethyl acetate溶媒

実験手順

4-Hydoxy-4-methylpiperidine hydrochloride (113 mg, 0.745 mmol) was suspended in N,N-dimethylformamide (3 ml), then triethylamine (1 ml) was added; benzotriazole-1-isooxytris(dimethylamino)phosphonium hexafluorophosphate (201 mg, 0.454 mmol) and ((4-(1-methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acid (145 mg, 0.378 mmol) were added thereto; and the reaction mixture was stirred at room temperature for 2 hours. After water was added to the reaction mixture, extraction was performed with ethyl acetate-tetrahydrofuran. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia NH silica gel; ethyl acetate, ethyl acetate:methanol=20:1, 10:1 in this order). After concentration under reduced pressure, the product was solidified with diethyl ether, suspended, filtered off, washed with diethyl ether, and dried under aeration to yield the title compound (137 mg, 0.285 mmol, 75.4%) as a colorless amorphous solid.

後処理

  1. washThe organic layer was washed with brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (Fuji Silysia NH silica gel
  5. concentrationAfter concentration under reduced pressure
  6. filtrationfiltered off
  7. washwashed with diethyl ether
  8. customdried under aeration

出典と根拠

ORDレコード
ord-b69e2511be7e4698b3b542ec288cabf7
出典データセット
uspto-grants-2006_09
特許番号
US07109219B2

反応ノート

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