Sodium Hydroxide → 4-{[4-(2-Methyl-thiazol-4-ylmethoxy)-1H-indole-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1929201ノート

反応式

HRID 1929201 の反応式
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[C:12]([C:18]([OH:20])=O)[NH:13]3)[N:6]=1.CC[N:23](C(C)C)C(C)C.[C:30]([O:34][C:35](=[O:43])NC1CCNCC1)([CH3:33])([CH3:32])[CH3:31].C1CN([P+](ON2N=[N:68][C:63]3[CH:64]=[CH:65][CH:66]=[CH:67]C2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[C:30]([O:34][C:35]([N:68]1[CH2:63][CH2:64][CH:65]([NH:23][C:18]([C:12]2[NH:13][C:14]3[C:10]([CH:11]=2)=[C:9]([O:8][CH2:7][C:5]2[N:6]=[C:2]([CH3:1])[S:3][CH:4]=2)[CH:17]=[CH:16][CH:15]=3)=[O:20])[CH2:66][CH2:67]1)=[O:43])([CH3:33])([CH3:32])[CH3:31]

参加物

8

反応物 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 2724699PyBOPHCID 668416854-(2-Methyl-thiazol-4-ylmethoxy)-1H-indole-2-carboxylic acid

生成物 1

HCID 668415664-{[4-(2-Methyl-thiazol-4-ylmethoxy)-1H-indole-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

4-(2-Methyl-thiazol-4-ylmethoxy)-1H-indole-2-carboxylic acid (170) (1.21 g, 4.2 mmol) is dissolved in 10 ml of DMF and the solution is cooled to 0° C. After addition of Huenigs base (2.16 ml, 12.6 mmol), piperidin-4-yl-carbamic acid tert-butyl ester (3) (841 mg, 4.2 mmol) and PyBOP (2.4 g, 4.6 mmol) the mixture is stirred at room temperature for 18 h. Ethyl acetate is added followed by concentrated sodium hydroxide, until a pH of 11 is reached. The organic layer is washed with brine, dried over sodium sulphate and evaporated under reduced pressure. The crude product is purified by flash-chromatography (silica gel, ethyl acetate/cyclohexane 1:1).

後処理

  1. washThe organic layer is washed with brine
  2. dry with materialdried over sodium sulphate
  3. customevaporated under reduced pressure
  4. customThe crude product is purified by flash-chromatography (silica gel, ethyl acetate/cyclohexane 1:1)

出典と根拠

ORDレコード
ord-3fe28e42720443f3ae42738666b695f2
出典データセット
uspto-grants-2012_05
特許番号
US08183366B2

反応ノート

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