Hydrochloric Acid → HCID 178483387, compound

HRID 1922363Notes

Reaction equation

HRID 1922363 reaction equation
[CH3:1][N:2]([CH3:34])[CH2:3][CH2:4][CH2:5][CH:6]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:16][C:17]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)=[NH:18])[CH:13]=2)[N:8](CC2C=CC(OC)=CC=2)[C:7]1=[O:33].C1(OC)C=CC=CC=1.[ClH:43]>FC(F)(F)C(O)=O.CO.C(Cl)Cl.C(Cl)Cl.CCOCC>[ClH:43].[ClH:43].[CH3:34][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:6]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:16][C:17]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)=[NH:18])[CH:13]=2)[NH:8][C:7]1=[O:33]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 7519AnisoleHCID 178490847HCID 178490847, compound

Product 1

HCID 178483387HCID 178483387, compoundYield 51.3%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of N-(3-(3-(dimethylamino)propyl)-1-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide (50 mg, 0.1 mmol) and anisole (23 μL, 0.2 mmol) in 7.5 mL trifluoroacetic acid was stirred at room temperature for 2 hours then heated at 60° C. for 22 hours. A TLC analysis indicated that only starting material is present. The mixture was concentrated and treated with 3N HCl and ethanol (5 mL) then heated at 60° C. for 4 hours. The yellow solution was treated with saturated NaHCO3 then extracted with 3×20 mL CH2Cl2. The combined organic layers were dried with MgSO4, filtered and concentrated to give a yellow residue. This residue was subjected to flash chromatography on silica gel using 5% 2M NH3 in MeOH/CH2Cl2 to give a light yellow solid. This compound was dissolved in CH2Cl2 (5 mL) and treated with 1 mL of a 1M HCl solution in Et2O to form a precipitate. The slurry was concentrated to give a yellow solid (22 mg, 51.3%). An HPLC analysis indicated that the product is >99% pure. An HPLC analysis indicated that the product is >99% pure. 1H-NMR (CD3OD) δ: 7.96-7.95 (d, J=4.5 Hz, 2H), 7.31 (pseudo t, J=4.2 Hz, 1H), 7.24 (br s, 1H), 7.17 (dd, J=1.5, 8.1 Hz, 1H), 7.00 (d, J=5.9 Hz, 1H), 3.17-3.10 (m, 2H), 2.85 (s, 6H), 2.91-2.83 (m, 2H) 2.67-2.60 (m, 1H), 1.91-1.56 (m, 4H).

Workup

  1. concentrationThe mixture was concentrated
  2. additiontreated with 3N HCl and ethanol (5 mL)
  3. temperaturethen heated at 60° C. for 4 hours
  4. additionThe yellow solution was treated with saturated NaHCO3
  5. extractionthen extracted with 3×20 mL CH2Cl2
  6. dry with materialThe combined organic layers were dried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow residue
  10. customto give a light yellow solid
  11. customto form a precipitate
  12. concentrationThe slurry was concentrated

Sources & evidence

ORD record
ord-1d03b7d7694d4801b2685bdd1f28cf07
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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