Trifluoroacetic acid → methyl 4-[3-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenyl]acetyl-4-thiazolidinyl]methoxybenzoate

HRID 350522Notes

Reaction equation

HRID 350522 reaction equation
C(O[C:6]([N:8]1[CH:12]([CH2:13][O:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=2)[CH2:11][S:10][CH2:9]1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=[O:26].C1[CH:33]=[CH:34][C:35]2N(O)N=N[C:36]=2[CH:37]=1.C(N([CH2:47][CH3:48])CC)C.[CH3:49][CH2:50][N:51]=[C:52]=[N:53][CH2:54][CH2:55][CH2:56]N(C)C.Cl.C1[CH2:65][O:64][CH2:63][CH2:62]1>C(Cl)Cl.CC#N>[CH3:65][O:64][C:63]1[CH:62]=[C:47]([CH2:48][C:6]([N:8]2[CH:12]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:23][CH:24]=3)[CH2:11][S:10][CH2:9]2)=[O:7])[CH:56]=[CH:55][C:54]=1[NH:53][C:52]([NH:51][C:50]1[CH:49]=[CH:37][CH:36]=[CH:35][C:34]=1[CH3:33])=[O:26]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23512106Methyl 4-(3-tert-butoxycarbonyl-4-thiazolidinyl)methoxybenzoate

Product 1

HCID 23511965methyl 4-[3-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenyl]acetyl-4-thiazolidinyl]methoxybenzoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of methyl 4-(3-tert-butoxycarbonyl-4-thiazolidinyl)methoxybenzoate (440 mg, 1.25 mmol) in CH2Cl2 (6 ml) was added TFA (3 ml) at 0° C. The reaction mixture was stirred at room temperature for 0.5 hr. The mixture was concentrated in vacuo. Sat. NaHCO3 was added to the residue, and extracted with CH2Cl2. The extract was washed with brine ,dried over Na2SO4, and concentrated in vacuo. The crude product was used to the subsequent reaction without further purification. To a stirred solution of the crude product (0.6 mmol), 3-methoxy-4-[N′-(2-methyl phenyl)uredio]phenylacetic acid (188 mg, 0.6 mmol), HOBt (81 mg, 0.6 mmol), and triethylamine (280 ml, 2.0 mmol) in THF (5 ml) and MeCN (5 ml) was added EDC.HCl (173 mg, 0.9 mmol) at 0° C. The reaction mixture was stirred at room temperature for 16 hr, and concentrated in vacuo. Water was added to the residue, and extracted with EtOAc. The extract was washed with sat. NaHCO3, 2-M citric acid, and sat. NaHCO3, then dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (1:3, v/v) as eluent to give methyl 4-[3-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenyl]acetyl-4-thiazolidinyl]methoxybenzoate (340 mg, quant) as an amorphous solid. 1H-NMR (CDCl3) δ 2.31 (s, 3H), 3.15–3.16 (m, 2H), 3.67–3.69 (m, 5H), 3.88 (s, 3H), 4.09–4.14 (m, 2H), 4.22–4.90 (m, 3H), 6.30 (m, 1H), 6.74–6.96 (m, 4H), 7.11–7.25 (m, 41H), 7.49–7.51 (m, 1H), 7.95–8.12 (m, 3H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionSat. NaHCO3 was added to the residue
  3. extractionextracted with CH2Cl2
  4. washThe extract was washed with brine ,dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was used to the subsequent reaction without further purification
  7. stirringThe reaction mixture was stirred at room temperature for 16 hr
  8. concentrationconcentrated in vacuo
  9. additionWater was added to the residue
  10. extractionextracted with EtOAc
  11. washThe extract was washed with sat. NaHCO3, 2-M citric acid, and sat. NaHCO3
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by column chromatography on silica gel with n-hexane-EtOAc (1:3

Sources & evidence

ORD record
ord-9fb40bd8ddff4b02aa76c1e700123143
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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