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

HRID 354457Notes

Reaction equation

HRID 354457 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) δ2.31 (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, 4H), 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
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was used to the subsequent reaction without further purification
  8. stirringThe reaction mixture was stirred at room temperature for 16 hr
  9. concentrationconcentrated in vacuo Water
  10. additionwas added to the residue
  11. extractionextracted with EtOAc
  12. washThe extract was washed with sat. NaHCO3, 2-M citric acid, and sat. NaHCO3
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by column chromatography on silica gel with n-hexane-EtOAc (1:3

Sources & evidence

ORD record
ord-1b729f5f9c65421187cfcb349d0cbb05
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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