Water → 4-{[5-({[(4-{4-[(4-Bromobutyl)oxy]butyl}phenyl)carbonyl]amino}methyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide

HRID 1675673노트

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HRID 1675673 반응식
[NH2:1][CH2:2][C:3]1[C:4]([NH:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([NH2:25])=[O:24])[CH2:19][CH2:18]2)=[C:5]2[CH:13]=[N:12][N:11]([CH2:14][CH3:15])[C:6]2=[N:7][C:8]=1[CH2:9][CH3:10].C(N(CC)CC)C.[Br:33][CH2:34][CH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]1[CH:51]=[CH:50][C:46]([C:47](Cl)=[O:48])=[CH:45][CH:44]=1.O>ClCCl>[Br:33][CH2:34][CH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]1[CH:44]=[CH:45][C:46]([C:47]([NH:1][CH2:2][C:3]2[C:4]([NH:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23]([NH2:25])=[O:24])[CH2:19][CH2:18]3)=[C:5]3[CH:13]=[N:12][N:11]([CH2:14][CH3:15])[C:6]3=[N:7][C:8]=2[CH2:9][CH3:10])=[O:48])=[CH:50][CH:51]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 580247604-{4-[(4-Bromobutyl)oxy]butyl}benzoyl chloride2회HCID 596832124-{[5-(Aminomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide2회

생성물 1

HCID 580247424-{[5-({[(4-{4-[(4-Bromobutyl)oxy]butyl}phenyl)carbonyl]amino}methyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide수율 68.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

A solution of 4-{[5-(aminomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide (0.21 g, 0.6 mmol, e.g. which can be as prepared in Intermediate 17) and triethylamine (0.21 ml, 1.52 mmol, 2.5 equivalents) in dichloromethane (20 ml) was stirred and cooled in an ice/water bath under an atmosphere of nitrogen. 4-{4-[(4-Bromobutyl)oxy]butyl}benzoyl chloride (0.32 g, 0.91 mmol, 1.5 equivalents, e.g. which can be as prepared in Intermediate 26) was added portion-wise over 2 minutes, and the mixture was stirred at 0° C. for 10 minutes and then at room temperature overnight. Iced water was added to the reaction mixture and the organic phase was separated and collected through a hydrophobic frit. The aqueous phase was extracted with dichloromethane (50 ml), and the combined organic extracts were evaporated to dryness to give a whitish foam. The residue was purified by passing through a 20 g silica column, eluting with a gradient of cyclohexane/ethyl acetate followed by a gradient of ethyl acetate/methanol. The fractions containing the product (obtained from 9:1 ethyl acetate/methanol) were pooled and evaporated to dryness to give the title compound as a pale yellow foam (0.27 g). LCMS showed MH+=656/658 (Bromine isotope pattern); TRET=2.88 min.

후처리

  1. temperaturecooled in an ice/water bath under an atmosphere of nitrogen
  2. customat room temperature
  3. customovernight
  4. customthe organic phase was separated
  5. customcollected through a hydrophobic frit
  6. extractionThe aqueous phase was extracted with dichloromethane (50 ml)
  7. customthe combined organic extracts were evaporated to dryness
  8. customto give a whitish foam
  9. customThe residue was purified
  10. washeluting with a gradient of cyclohexane/ethyl acetate
  11. additionThe fractions containing
  12. customthe product (obtained from 9:1 ethyl acetate/methanol)
  13. customevaporated to dryness

출처 및 근거

ORD 기록
ord-acd23be4643849b39891fc10fae99117
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003663B2

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