Hydrochloric Acid → HCID 178499061, compound

HRID 2289797Notes

Reaction equation

HRID 2289797 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([CH2:14][NH:15][C:16]3([C:21]([OH:23])=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:11][CH:12]=2)[C:7]([NH:24][C:25]([NH2:27])=[NH:26])=[N:6][CH:5]=1.Cl.N[C:30](N)=N.COC(=O)C1(CCCC1)NCC1C=C2C(C(Cl)=CN=C2Cl)=CC=1.Cl>CS(C)=O.C(Cl)Cl.CO.O>[CH3:30][O:22][C:21](=[O:23])[C:16]1([CH2:17][CH2:18][CH2:19][CH2:20]1)[NH:15][CH2:14][C:10]1[CH:9]=[C:8]2[C:13]([C:4]([Cl:3])=[CH:5][N:6]=[C:7]2[NH:24][C:25]([NH2:27])=[NH:26])=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 5742Guanidine HydrochlorideHCID 18698266HCID 18698266, compoundHCID 178478800HCID 178478800, compound

Product 1

HCID 178499061HCID 178499061, compoundYield 4.6%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
50 °C

Procedure

N-({4-Chloro-1-guanidino-7-isoquinolinyl}methyl)cycloleucine dihydrochloride ##STR99## NaH (52 mg, 80% dispersion in mineral oil, 1.73 mmol) was added to a slurry of guanidine hydrochloride (265 mg, 2.77 mmol) in DMSO (2.5 ml) and the mixture heated to 50° C. for 20 mins. N-[(1,4-Dichloro-7-isoquinolinyl)methyl]cycloleucine methyl ester (245 mg, 0.69 mmol) in DMSO (2.5 ml) was added and after heating at 90° C. for 41/2 h, the solution was poured into water (50 ml). The mixture was extracted with EtOAc (2×), the combined organic extracts washed with water, brine and then dried (Na2SO4). The residue was purified by column chromatography upon silica gel eluting with CH2Cl2 -MeOH -0.880 NH3 (90:10:1) to give a yellow solid. This was dissolved in a CH2Cl2 -MeOH solution and acidified with ethereal HCl (1N), concentrated in vacuo and the crude product recrystallised from EtOH to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)methyl]cycloleucine methyl ester (30 mg, 0.08 mmol) as a cream solid.

Workup

  1. temperatureafter heating at 90° C. for 41/2 h
  2. extractionThe mixture was extracted with EtOAc (2×)
  3. washthe combined organic extracts washed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customThe residue was purified by column chromatography upon silica gel eluting with CH2Cl2 -MeOH -0.880 NH3 (90:10:1)
  6. customto give a yellow solid
  7. concentrationconcentrated in vacuo
  8. customthe crude product recrystallised from EtOH

Sources & evidence

ORD record
ord-75033c3e84c44d109775a53293c8c37d
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

Loading…