Water → 4-{4-[(4-Bromobutyl)oxy]butyl}-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}benzamide

HRID 1675672Notes

Reaction equation

HRID 1675672 reaction equation
[NH2:1][CH2:2][C:3]1[C:8]([CH2:9][CH3:10])=[N:7][C:6]2[N:11]([CH2:14][CH3:15])[N:12]=[CH:13][C:5]=2[C:4]=1[NH:16][CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C(N(CC)CC)C.[Br:30][CH2:31][CH2:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]1[CH:48]=[CH:47][C:43]([C:44](Cl)=[O:45])=[CH:42][CH:41]=1.O>ClCCl>[Br:30][CH2:31][CH2:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]1[CH:48]=[CH:47][C:43]([C:44]([NH:1][CH2:2][C:3]2[C:4]([NH:16][CH:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]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:45])=[CH:42][CH:41]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 580247604-{4-[(4-Bromobutyl)oxy]butyl}benzoyl chloride2×HCID 596832145-(Aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine2×

Product 1

HCID 580247474-{4-[(4-Bromobutyl)oxy]butyl}-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}benzamideYield 42.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (300 mg, 1 mmol, e.g. which can be as prepared in Intermediate 7) and triethylamine (0.34 ml, 2.5 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 (520 mg, 1.5 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 5 minutes and then at room temperature for 3 hours. 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 (10 ml), and the organic layers were combined and evaporated to dryness to give a brown oil. The residue was purified by flash chromatography (100 g silica cartridge, FlashMaster II), eluting with a gradient of 0-100% ethyl acetate in cyclohexane over 40 minutes. The fractions containing the product were combined and evaporated to dryness to give the title compound as a glass (0.26 g). LCMS showed MH+=614/616 (Bromine isotope pattern); TRET=3.06 min.

Workup

  1. temperaturecooled in an ice/water bath under an atmosphere of nitrogen
  2. waitat room temperature for 3 hours
  3. customthe organic phase was separated
  4. customcollected through a hydrophobic frit
  5. extractionThe aqueous phase was extracted with dichloromethane (10 ml)
  6. customevaporated to dryness
  7. customto give a brown oil
  8. customThe residue was purified by flash chromatography (100 g silica cartridge, FlashMaster II)
  9. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane over 40 minutes
  10. additionThe fractions containing the product
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-412d8589126c4b348d56bdbdae7c2844
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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