Hydrochloric Acid → (+/-)-trans-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine hydrochloride

HRID 546502Notes

Reaction equation

HRID 546502 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.FC(F)(F)C(O)=O.[CH3:44][N:45]1[CH2:50][CH2:49][C:48]2[N:51]=[C:52]([C:54]([NH:56][C@@H:57]3[CH2:62][CH2:61][CH2:60][CH2:59][C@H:58]3[NH2:63])=[O:55])[S:53][C:47]=2[CH2:46]1.Cl>CN(C)C=O.C(N(CC)CC)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:63][C@@H:58]1[CH2:59][CH2:60][CH2:61][CH2:62][C@H:57]1[NH:56][C:54]([C:52]1[S:53][C:47]3[CH2:46][N:45]([CH3:44])[CH2:50][CH2:49][C:48]=3[N:51]=1)=[O:55])=[O:13])=[CH:5]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 18442875(+/-)-trans-N-[(5-methyl-4,5,6,7-tetrahydrothiazolo-[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine trifluoroacetate

Product 1

HCID 68451269(+/-)-trans-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine hydrochlorideYield 143.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

5-Chloroindole-2-carboxylic acid (109 mg), 1-hydroxybenzotriazole monohydrate (9 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (321 mg) and triethylamine (0.232 ml) were added to a solution with (±)-trans-N-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine trifluoroacetate (300 mg) dissolved in N,N-dimethylformamide (20 ml), and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure using a vacuum pump, and dichloromethane and water were added to the residue to conduct liquid separation. The resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (dichloromethane:methanol=25:1) to obtain a colorless foamy substance. 1N hydrochloric acid (1 ml) was added to this substance and the solvent was distilled off under reduced pressure to obtain the title compound (203 mg) as a pale brown foamy substance.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionwere added to the residue
  3. customliquid separation
  4. dry with materialThe resultant organic layer was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (dichloromethane:methanol=25:1)
  7. customto obtain a colorless foamy substance
  8. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-55bc5f4f9a0d4674b9d4fa0b4d86cd3d
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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