Triethylamine → N-{[3-bromo-4-(methyloxy)phenyl]methyl}-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide

HRID 662099Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 662099
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:32][CH3:33])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[N:28]=[C:27]([C:29](O)=[O:30])[CH:26]=[CH:25][CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[Br:64][C:65]1[CH:66]=[C:67]([CH2:73][NH2:74])[CH:68]=[CH:69][C:70]=1[O:71][CH3:72]>ClCCl>[Br:64][C:65]1[CH:66]=[C:67]([CH2:73][NH:74][C:29]([C:27]2[CH:26]=[CH:25][CH:24]=[C:23]([C:21]([NH:20][CH2:19][C:10]3[C:11]([NH:12][CH:13]4[CH2:14][CH2:15][O:16][CH2:17][CH2:18]4)=[C:6]4[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]4=[N:8][C:9]=3[CH2:32][CH3:33])=[O:22])[N:28]=2)=[O:30])[CH:68]=[CH:69][C:70]=1[O:71][CH3:72]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 24721672(3-Bromo-4-methoxyphenyl)methanamine hydrochlorideHCID 578193746-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid

Produkt 1

HCID 57819364N-{[3-bromo-4-(methyloxy)phenyl]methyl}-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamideAusbeute 121,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid (30 g, 66.3 mmol) in a 1 L round-bottom flask in dichloromethane (DCM) (300 mL) was added triethylamine (46.2 mL, 331 mmol) giving a solution to which was added TBTU (31.9 g, 99 mmol). The mixture became cloudy and was then stirred at room temperature under nitrogen for 5 min when 1-[3-bromo-4-(methyloxy)phenyl]methanamine hydrochloride (18.42 g, 72.9 mmol) was added. After 1.5 h the reaction was worked up. The mixture was partitioned between dichloromethane and water and the aqueous layer extracted well with dichloromethane. The combined organics were washed with saturated sodium bicarbonate, brine, dried (MgSO4), filtered and evaporated to give 52.41 g (121%) of a golden foam. The crude product was purified on a 750 g Companion XL silica cartridge, eluting with 20-100% of {1% MeOH in EtOAc) in dichloromethane over 12 column volumes. The fractions were checked by HPLC and product fractions were combined and solvent evaporated to give 30.15 g (˜65%) of a cream foam that lab HPLC showed to be 97.2% pure (ret time 2.11 min) LC-MS m/z 650, 652 (M+H)+, 1.03 min (ret time).

Aufarbeitung

  1. customgiving a solution to which
  2. additionwas added
  3. customThe mixture was partitioned between dichloromethane and water
  4. extractionthe aqueous layer extracted well with dichloromethane
  5. washThe combined organics were washed with saturated sodium bicarbonate, brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-cbfaf14e31df4801b8d096ad561c59b7
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084449B2

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