Bis(2-Methoxyethyl)amine → HCID 68714954, compound

HRID 2101206Notes

Reaction equation

HRID 2101206 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7][O:8][CH3:9].[Br:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15]Br)=[CH:13][CH:12]=1.CN(C=[O:23])C>>[Br:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][N:5]([CH2:6][CH2:7][O:8][CH3:9])[C:4](=[O:23])[CH2:3][O:2][CH3:1])=[CH:13][CH:12]=1

Participants

4

Reactant 3

HCID 2383Bis(2-Methoxyethyl)amineHCID 6228DimethylformamideHCID 685274-Bromobenzyl bromide

Product 1

HCID 68714954HCID 68714954, compound

Procedure

Di-(2-methoxyethyl)amine (6 ml) was added to a solution of 4-bromobenzylbromide (5 g) in DMF (20 ml) at ambient temperature. After stirring at ambient temperature for 2 h, the mixture was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution. The organic phase was dried, the solvent removed under vacuum to yield a yellow oil which was purified by column chromatography using a 0 to 20% ethyl acetate/isohexane gradient to yield the title compound as a clear oil (4.83 g). MS (M+H)+302. 1H NMR (CDCl3) 2.72 (t, 4H), 3.3 (s, 6H), 3.45 (t, 4H), 3.64 (s, 2H), 7.21 (d, 2H), 7.41 (d, 2H). b) 2-[(Aminocarbonyl)amino]-5-{4-[(bis-(2-methoxyethyl)amino)methyl]phenyl}-thiophene-3-carboxamide A solution of N-(4-bromobenzyl)-2-methoxy-N-(2-methoxyethyl)ethanamide (1.6 g) in THF (15 ml) was cooled to −60° C. under argon. Butyl lithium (5 ml, 1.6M solution in hexane) was added dropwise and the mixture was stirred at −60° C. for a further 20 min Triisopropylborate (1.8 ml) was added before allowing the mixture to warm to room temperature. After stirring at room temperature for 3.5 h, the THF was removed under vacuum and DME (20 ml), water (2 ml) and 2-(aminocarbonyl)amino-5-bromo-thiophene-3-carboxamide (0.47 g) were added. The mixture was degassed by purging with argon and sonicating for 15 min, sodium hydrogen carbonate (0.445 g) and Pd(Ph3)4 (0.1 g) added and heated to 90° C. for 18 h under argon. The solvent was removed under vacuum and the residue was partitioned between 2N sodium hydroxide solution and DCM. The combined phases were filtered and the aqueous phase was taken to pH 7 by addition of 5N aqueous hydrochloric acid. A precipitate formed which was purified by preparative hplc to yield the product as a solid (0.01 g). MS (M+H)+407. 1H NMR (DMSO-D6) 2.62 (t, 4H), 3.19 (s, 6H), 3.39 (t, 4H), 3.61 (s, 2H), 6.87-6.95 (bs, 2H), 7.22-7.31 (m, 3H), 7.44 (d, 2H), 7.61-6.9 (m, 2H), 10.97 (s,1H).

Workup

  1. customthe mixture was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution
  2. customThe organic phase was dried
  3. customthe solvent removed under vacuum
  4. customto yield a yellow oil which
  5. customwas purified by column chromatography

Sources & evidence

ORD record
ord-92be4e93f19a43b193630576185e3afd
Source dataset
uspto-grants-2009_08
Patent number
US07572826B2

Reaction notes

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