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

HRID 1675663Notes

Reaction equation

HRID 1675663 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-8152df15a9d9471f96416ad8c05d1d9d
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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