2-(Dimethylamino)ethanol → Ammonia

HRID 1888612Notes

Reaction equation

HRID 1888612 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH3:8])[CH2:5][CH2:6][OH:7].Cl[C:10]1[CH:15]=[CH:14][N:13]=[CH:12][C:11]=1[C:16]1[N:24]=[CH:23][C:22]2[NH:21][C:20]3[N:25]=[CH:26][C:27]([C:29]4[CH:30]=[N:31][N:32]([CH3:34])[CH:33]=4)=[CH:28][C:19]=3[C:18]=2[CH:17]=1>CN(C=O)C>[NH3:4].[CH3:3][N:4]([CH3:8])[CH2:5][CH2:6][O:7][C:10]1[CH:15]=[CH:14][N:13]=[CH:12][C:11]=1[C:16]1[N:24]=[CH:23][C:22]2[NH:21][C:20]3[N:25]=[CH:26][C:27]([C:29]4[CH:30]=[N:31][N:32]([CH3:34])[CH:33]=4)=[CH:28][C:19]=3[C:18]=2[CH:17]=1

Participants

6

Reactant 3

HCID 79022-(Dimethylamino)ethanol2×HCID 24758Sodium hydride2×HCID 670275236-(4-Chloro-pyridin-3-yl)-3-(1-methyl-1H-pyrazol-4-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 2

HCID 222AmmoniaHCID 44546491Dimethyl-(2-{3-[3-(1-methyl-1H-pyrazol-4-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl]-pyridin-4-yloxy}-ethyl)-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 38 mg, 0.96 mmol) was added to a solution of N,N-dimethylethanolamine (63 mg, 0.71 mmol) in DMF (5 mL) and the mixture stirred at ambient temperature for 75 minutes. 6-(4-chloro-pyridin-3-yl)-3-(1-methyl-1H-pyrazol-4-yl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (85 mg, 0.24 mmol) was added and the reaction mixture was stirred at ambient temperature for 26 h then at 80° C. for 2 h. After this time, the reaction mixture was added to a solution of N,N-dimethylethanolamine (0.48 mL) and sodium hydride (60% dispersion in mineral oil, 288 mg) in DMF (2 mL), which had been pre-stirred for 15 minutes. The reaction mixture was stirred at 80° C. overnight before being poured onto water and the resultant solid collected by filtration. The material was purified by flash chromatography (silica, 12 g column, ISCO, 0-20% methanol in DCM then 20% (2N ammonia in methanol) in DCM) to afford the title compound as a yellow oil which crystallised on standing (0.1 g, 58%). 1H NMR (CD3OD, 400 MHz): 8.94 (d, J=1.1 Hz, 1H), 8.81-8.77 (m, 2H), 8.71 (s, 1H), 8.58 (d, J=1.1 Hz, 1H), 8.48 (d, J=5.9 Hz, 1H), 8.09 (s, 1H), 7.94 (s, 1H), 7.28 (d, J=5.9 Hz, 1H), 4.42 (t, J=5.2 Hz, 2H), 3.98 (s, 3H), 3.03 (t, J=5.1 Hz, 2H), 2.42 (s, 6H). LCMS (Method A): RT=3.93 min, M+H+=414.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 26 h
  2. waitat 80° C. for 2 h
  3. stirringhad been pre-stirred for 15 minutes
  4. stirringThe reaction mixture was stirred at 80° C. overnight
  5. additionbefore being poured onto water
  6. filtrationthe resultant solid collected by filtration
  7. customThe material was purified by flash chromatography (silica, 12 g column, ISCO, 0-20% methanol in DCM

Sources & evidence

ORD record
ord-f6ba00f0c4f0410b8e1f8ef319e91786
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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