Citric Acid → HCID 59000997, compound

HRID 1893838Notes

Reaction equation

HRID 1893838 reaction equation
[C:1]([C@H:4]([N:9]([CH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=1)[S:10]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[CH2:5][CH:6]([CH3:8])[CH3:7])(=[O:3])[NH2:2].[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([S:10]([N:9]([C@H:4]([CH2:5][CH:6]([CH3:7])[CH3:8])[C:1]([NH2:2])=[O:3])[CH2:20][C:21]2[CH:29]=[CH:28][C:24]([C:25]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[O:27])=[CH:23][CH:22]=2)(=[O:12])=[O:11])=[CH:14][CH:15]=1

Participants

8

Reactant 6

HCID 311Citric AcidHCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59001039HCID 59001039, compound

Product 1

HCID 59000997HCID 59000997, compoundYield 79.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 0° C. solution of 4-{[N-((1R)-1-carbamoyl-3-methyl-butyl)-N-(4-chlorobenzenesulfonyl)amino}-methyl]benzoic acid (50.0 mg, 0.114 mmol) in DMF (0.3 mL) was added morpholine (12.9 mg, 0.148 mmol), followed by 1-hydroxybenzotriazole (18.5 mg, 0.137 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (26.2 mg, 0.137 mmol), and iPr2NEt (26 μL, 0.15 mmol). After 2 h, the solution was warmed to rt. After 4 h, the solution was poured into 10% aq. citric acid and extracted with EtOAc (2×). The combined organic layers were washed sequentially with water and sat. aq. NaHCO3, then dried (MgSO4) and concentrated. Flash column chromatography (SiO2, 40 to 100% EtOAc/hexanes) gave the title compound as a white solid (46.0 mg, 79%). MS (ESI), (M+H)+508.22; 1H NMR (CDCl3, 300 MHz) δ 7.68 (d, 2H, J=8.6), 7.29-7.47 (m, 6H), 6.38 (br s, 1H), 5.75 (br s, 1H), 4.65 (d, 1H, J=16.0), 4.42 (d, 1H, J=16.0), 4.32 (t, 1H, J=7.5), 3.30-3.85 (br m, 8H), 1.69-1.78 (m, 1H), 1.28-1.37 (m, 1H), 1.08-1.14 (m, 1H), 0.76 (d, 3H, J=6.5), 0.63 (d, 3H, J=6.6).

Workup

  1. waitAfter 4 h
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed sequentially with water and sat. aq. NaHCO3
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8608eb86e12540d98491b92a7926855d
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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