Lithium Hydroxide → 3-({5-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid methyl ester

HRID 1061722Notes

Reaction equation

HRID 1061722 reaction equation
CO[C:3]([C:5]1[S:6][C:7]([C:10](=[O:21])[NH:11][CH2:12][CH2:13][NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[CH:8][CH:9]=1)=[O:4].[Li+].[OH-].N1C=CC=CC=1NCCNC(C1SC(C(O)=O)=CC=1)=O.C(OC(NC[CH2:53][O:54][C:55](=[O:72])[CH:56]([NH:59][S:60]([C:63]1[C:68]([CH3:69])=[CH:67][C:66]([CH3:70])=[CH:65][C:64]=1[CH3:71])(=[O:62])=[O:61])[CH2:57][NH2:58])=O)(C)(C)C.OC1C2N=NNC=2C=CC=1.Cl.C(N=C=N)C>CN(C=O)C>[CH3:53][O:54][C:55](=[O:72])[CH:56]([NH:59][S:60]([C:63]1[C:68]([CH3:69])=[CH:67][C:66]([CH3:70])=[CH:65][C:64]=1[CH3:71])(=[O:62])=[O:61])[CH2:57][NH:58][C:3]([C:5]1[S:6][C:7]([C:10](=[O:21])[NH:11][CH2:12][CH2:13][NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[CH:8][CH:9]=1)=[O:4]

Participants

8

Reactant 6

HCID 3939Lithium HydroxideHCID 206776163-Amino-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid 2-tert-butoxycarbonylamino-ethyl esterHCID 21883477Ethylcarbodiimide hydrochlorideHCID 233982735-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carboxylic acid methyl esterHCID 542453455-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 537556273-({5-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid methyl esterYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carboxylic acid methyl ester was hydrolyzed with LiOH as described before. To a mixture of 5-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carboxylic acid (38 mg, 0.12 mmol), salt of 3-amino-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid 2-tert-butoxycarbonylamino-ethyl ester (47 mg, 0.14 mmol), hydroxybenzotriazole (21 mg, 0.15 mmol) in DMF (20 mL), was added 1-(3-dimethylamino) propyl)-3-ethylcarbodiimide hydrochloride (29 mg, 0.15 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 (10% MeOH/EtOAc) gave 60 mg (87%) of pure 3-({5-[2-(Pyridin-2-ylamino)-ethylcarbamoyl]-thiophene-2-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid methyl ester. 1HNMR (300 MHz, CDCl3) δ: 2.22 (s, 3H), 2.61 (s, 6H), 3.55 (m, 4H), 3.82 (m, 1H), 4.09 (m, 1H), 6.50(d, 1H), 6.69(t, 1H), 6.90(s, 2H), 7.05(t, 1H), 7.40(m, 3H), 8.10 (s, 1H), 8.43(m, 1H).

Workup

  1. customInsolubles were removed by filtration
  2. customthe solvent was evaporated
  3. customPurification of the residue on silica gel (10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-cd1649773cca4f5ab7e4db6d498e54d7
Source dataset
uspto-grants-2005_11
Patent number
US06960594B2

Reaction notes

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