Diisopropylethylamine → Ethyl 4-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)amino]-1,6-diethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

HRID 1675663ノート

反応式

HRID 1675663 の反応式
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH2:13][CH3:14])[N:5]=[C:4]2[N:15]([CH2:18][CH3:19])[N:16]=[CH:17][C:3]=12.C(N(CC)C(C)C)(C)C.[NH2:29][CH:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1.[Cl-].[Li+]>CN1CCCC1=O>[CH3:42][C:39]([O:38][C:36]([N:33]1[CH2:34][CH2:35][CH:30]([NH:29][C:2]2[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH2:13][CH3:14])[N:5]=[C:4]3[N:15]([CH2:18][CH3:19])[N:16]=[CH:17][C:3]=23)[CH2:31][CH2:32]1)=[O:37])([CH3:40])[CH3:41]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 12682914-Amino-1-Boc-piperidineHCID 59683218Ethyl 4-chloro-1,6-diethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate2 回

生成物 1

HCID 59683219Ethyl 4-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)amino]-1,6-diethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
120 °C

実験手順

A solution of ethyl 4-chloro-1,6-diethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (14.8 g, 52.6 mmol, e.g. which can be as prepared in Intermediate 3, first or alternative preparation thereof) in N-methyl-2-pyrrolidinone (140 ml) was treated with N,N-diisopropylethylamine (22.9 ml, 131 mmol) followed by 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (11.6 g, 57.9 mmol, commercially available e.g. from AstaTech) and the mixture was heated at 120° C. for 24 hours. The reaction mixture was cooled and poured into aqueous lithium chloride solution (5% LiCl, 1 L) and the aqueous phase was extracted with ethyl acetate (3×250 ml). The combined organic extracts were dried (Na2SO4) and the solvent was evaporated. The residue, an oil, was purified by column chromatography using a column of silica gel (ART9385, 500 ml) made up in 4:1 hexane:ethyl acetate, eluting with 4:1 hexane:ethyl acetate (500 ml) and then 2:1 hexane:ethyl acetate until the product eluted. The fractions containing the product were pooled and the solvent was evaporated to give the title compound (18.55 g) as an oil which solidified on standing. LCMS m/z 446 [MH+]; TRET=3.69 min.

後処理

  1. customfirst or alternative preparation
  2. temperatureThe reaction mixture was cooled
  3. extractionthe aqueous phase was extracted with ethyl acetate (3×250 ml)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. customthe solvent was evaporated
  6. customThe residue, an oil, was purified by column chromatography
  7. washethyl acetate, eluting with 4:1 hexane
  8. washethyl acetate (500 ml) and then 2:1 hexane:ethyl acetate until the product eluted
  9. additionThe fractions containing the product
  10. customthe solvent was evaporated

出典と根拠

ORDレコード
ord-8152df15a9d9471f96416ad8c05d1d9d
出典データセット
uspto-grants-2011_08
特許番号
US08003663B2

反応ノート

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