tert-butyl N-[2-(pyridin-2-ylamino)ethyl]carbamate → 5-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carboxylic acid methyl ester

HRID 1061721Notes

Reaction equation

HRID 1061721 reaction equation
C(O[C:6](=[O:17])[NH:7][CH2:8][CH2:9][NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)(C)(C)C.[C:18](O)(C(F)(F)F)=O.C(Cl)Cl.C[C:29]1[C:30](C(O)=O)=[C:31]([C:34]([OH:36])=[O:35])[S:32][CH:33]=1.OC1C2N=NNC=2C=CC=1.Cl.C(N=C=N)C>CN(C=O)C>[CH3:18][O:36][C:34]([C:31]1[S:32][C:33]([C:6](=[O:17])[NH:7][CH2:8][CH2:9][NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)=[CH:29][CH:30]=1)=[O:35]

Participants

7

Reactant 5

HCID 18419519tert-butyl N-[2-(pyridin-2-ylamino)ethyl]carbamateHCID 21863450Trifluoroacetic acid methylene chlorideHCID 21883477Ethylcarbodiimide hydrochlorideHCID 22285229Mono methylthiophene dicarboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 233982735-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carboxylic acid methyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [2-(Pyridin-2-ylamino)-ethyl]-carbamic acid tert-butyl ester (44 mg, 0.14 mmol) was mixed with a mixture of (1:1)TFA/CH2Cl2 (30 mL) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was tritured with dry ether (2×30 mL). This gave 35 mg (95%) of pure trifluoroacetate salt. The salt was neutralized with DIEA and treated with mono methylthiophene dicarboxylic acid (32 mg, 0.17 mmol), hydroxybenzotriazole (24 mg, 0.17 mmol) in DMF (20 mL). To this mixture was added 1-(3-dimethylamino) propyl)-3-ethylcarbodiimide hydrochloride (33 mg, 0.17 mmol). The reaction was stirred overnight at room temperature. Insolubles were removed by filtration and the solvent was evaporated. Purification of the residue on silica gel (5% MeOH/EtOAc) gave 38 mg (88%) of pure 5-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carboxylic acid methyl ester. 1HNMR (300 MHz, CDCl3) δ: 3.43 (m, 2H), 3.51 (m, 2H), 3.92 (s, 3H), 6.45(d, 1H) 6.80(t, 1H), 7.42(t, 1H), 7.45 (s, 1H), 7.55 (s, 1H), 8.10 (s, 1H).

Workup

  1. customThe solvent was evaporated
  2. stirringThe reaction was stirred overnight at room temperature
  3. customInsolubles were removed by filtration
  4. customthe solvent was evaporated
  5. customPurification of the residue on silica gel (5% MeOH/EtOAc)

Sources & evidence

ORD record
ord-61e4827a713b42588dcd7849b03090ea
Source dataset
uspto-grants-2005_11
Patent number
US06960594B2

Reaction notes

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