Hydrochloric Acid → HCID 59464153, compound

HRID 1713758Notes

Reaction equation

HRID 1713758 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[C:25](=[O:30])[C:26]([O:28][CH3:29])=O.Cl.O.[NH2:33][NH2:34].[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[N:42]=C=S.CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C=O)C>[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[NH:42][C:29]1[O:28][C:26]([C:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:6][CH:7]=2)=[O:30])=[N:34][N:33]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 24654Hydrazine hydrate (1:1)HCID 79846Methyl chloroglyoxylateHCID 81531DiisopropylethylamineHCID 88628Methyl 4-aminobenzenebutanoateHCID 975202-Fluorophenyl isothiocyanate

Product 1

HCID 59464153HCID 59464153, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Methyl 4-(4-aminophenyl)butanoate (Journal of Medicinal Chemistry (1990), 33(11), 3014-19) (193 mg, 1 mmol) was stirred in dry DCM (9 mL) and PS-di-isopropylethylamine (750 mg, 3 mmol) was added. Methyl chloro(oxo)acetate (101 μl, 1.1 mmol) was added to the reaction mixture which was then stirred at room temperature for 2 h. The polymer supported base (HCl salt) was filtered off and washed with DCM (3 mL). Hydrazine monohydrate (53 μL, 1.1 mmol) was added to the stirred filtrate and a white precipitate formed after 2 h. The reaction mixture was stirred at room temperature overnight then DMF (5 mL) was added to dissolve the solid. 2-Fluorophenylisothiocyanate (0.135 mL, 1.1 mmol) was added via a pipette and the mixture stirred at room temperature for 2.5 h before adding EDAC (230 mg, 1.2 mmol). After stirring at room temperature for a further 2.5 h the mixture was heated to 50° C. and the DCM was allowed to evaporate. After 2 h the reaction had gone to completion and the mixture was concentrated in vacuo. The orange solid obtained was crystallised from water and then filtered. The solid was then washed with Et2O, EtOAc and then MeCN (1 mL) to give the title compound (174 mg, 44%) as a solid; 1H NMR δ 1.79-1.87 (2H, m), 2.31 (2H, t), 2.58 (2H, t), 3.59 (3H, s), 7.15-7.20 (3H, m), 7.25-7.34 (2H, m), 7.71 (2H, d), 8.02-8.07 (1H, m), 10.76 (1H, s), 10.95 (1H, s); MS m/e MH+ 399.

Workup

  1. filtrationwas filtered off
  2. washwashed with DCM (3 mL)
  3. customa white precipitate formed after 2 h
  4. stirringThe reaction mixture was stirred at room temperature overnight
  5. dissolutionto dissolve the solid
  6. stirringthe mixture stirred at room temperature for 2.5 h
  7. stirringAfter stirring at room temperature for a further 2.5 h the mixture
  8. temperaturewas heated to 50° C.
  9. customto evaporate
  10. waitAfter 2 h the reaction had gone to completion
  11. concentrationthe mixture was concentrated in vacuo
  12. customThe orange solid obtained
  13. customwas crystallised from water
  14. filtrationfiltered
  15. washThe solid was then washed with Et2O, EtOAc

Sources & evidence

ORD record
ord-45f65f383d7e4e719749743503aae8a4
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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