2-(Methylamino)ethanol → HCID 23729488, compound

HRID 1675688Notes

Reaction equation

HRID 1675688 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([NH:11][C:12]1[CH:41]=[CH:40][C:15]([C:16]([NH:18][CH2:19][C:20]2[C:21]([NH:33][CH:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:22]3[CH:30]=[N:29][N:28]([CH2:31][CH3:32])[C:23]3=[N:24][C:25]=2[CH2:26][CH3:27])=[O:17])=[CH:14][CH:13]=1)=[O:10].[CH3:42][NH:43][CH2:44][CH2:45][OH:46].C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH2:31]([N:28]1[C:23]2=[N:24][C:25]([CH2:26][CH3:27])=[C:20]([CH2:19][NH:18][C:16](=[O:17])[C:15]3[CH:40]=[CH:41][C:12]([NH:11][C:9](=[O:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:43]([CH2:44][CH2:45][OH:46])[CH3:42])=[CH:13][CH:14]=3)[C:21]([NH:33][CH:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:22]2[CH:30]=[N:29]1)[CH3:32]

Participants

5

Reactant 3

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 58024751HCID 58024751, compound3×

Product 1

HCID 23729488HCID 23729488, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
85 °C

Procedure

4-[(8-Bromooctanoyl)amino]-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}benzamide (100 mg, 0.16 mmol, e.g. which can optionally be as prepared in Intermediate 11) was dissolved in N,N-dimethylformamide (4 ml). To one-quarter of this solution, i.e. containing 4-[(8-bromooctanoyl)amino]-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}benzamide (25 mg, 0.04 mmol) in N,N-dimethylformamide (1 ml), was added 2-(methylamino)ethanol (0.0064 ml (6.4 microliters), 0.08 mmol, 2 equivalents, commercially available e.g. from Aldrich) followed by N,N-diisopropylethylamine (0.04 ml, about 6 equivalents). The reaction mixture was heated at 85° C. for 16 hours. The solvent was evaporated and the residue was purified by eluting through a 5 g silica SPE cartridge, with dichloromethane containing 20% methanol and 1% triethylamine as the eluent, to give the title compound (18.7 mg), in the form of a cream foam, initially thought to be in the form of the “free base”. LCMS showed MH+=622; TRET=2.20 min. However, later re-inspection of the 1H NMR spectrum suggests that the product was isolated as a salt e.g. a mono-salt (presumed to be a hydrobromide salt), e.g. from the signals of protons adjacent to the (2-hydroxyethyl)(methyl)amino group.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified
  3. washby eluting through a 5 g silica SPE cartridge, with dichloromethane containing 20% methanol and 1% triethylamine as the eluent

Sources & evidence

ORD record
ord-90d7621273df41cda7997e9b227c6b7a
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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