Tetrahydrofuran → (+/-)-cis-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[[5-[2-(methoxycarbonylamino)ethyl]-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl]carbonyl]-1,2-cyclohexane-diamine hydrochloride

HRID 546517Notes

Reaction equation

HRID 546517 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][C:8]2[N:11]=[C:12]([C:14]([NH:16][C@@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]3[NH:23][C:24]([C:26]3[NH:27][C:28]4[C:33]([CH:34]=3)=[CH:32][C:31]([Cl:35])=[CH:30][CH:29]=4)=[O:25])=[O:15])[S:13][C:7]=2[CH2:6]1.C(N(CC)CC)C.Cl[C:44](Cl)([O:46][C:47](=O)[O:48]C(Cl)(Cl)Cl)Cl.O1CCCC1>N1C=CC=CC=1.Cl.CO>[ClH:35].[Cl:35][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([C:24]([NH:23][C@@H:18]1[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]1[NH:16][C:14]([C:12]1[S:13][C:7]3[CH2:6][N:5]([CH2:4][CH2:3][NH:2][C:47]([O:46][CH3:44])=[O:48])[CH2:10][CH2:9][C:8]=3[N:11]=1)=[O:15])=[O:25])=[CH:34]2

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 94429TriphosgeneHCID 67056679HCID 67056679, compound

Product 1

HCID 68909378(+/-)-cis-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[[5-[2-(methoxycarbonylamino)ethyl]-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl]carbonyl]-1,2-cyclohexane-diamine hydrochlorideYield 75.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

(±)-cis-N1-[[5-(2-Aminoethyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl]carbonyl]-N2-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclohexanediamine hydrochloride (144 mg) was dissolved in pyridine (3 ml), triethylamine (138 μl) was added, and the mixture was stirred at room temperature for 5 minutes. A solution prepared by adding triphosgene (49 mg) to tetrahydrofuran (1 ml) containing methanol (20 μl) was added dropwise to this solution. The reaction mixture was stirred at room temperature for 1 hour, then concentrated under reduced pressure, and the residue was dissolved in a 9:1 mixed solvent of dichloromethane and methanol. Water was added to the solution 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=100:3) to obtain a colorless foamy substance. This product was suspended in 1N hydrochloric acid (0.2 ml), and the suspension was concentrated under reduced pressure to obtain the title compound (60 mg) as a pale yellow foamy substance.

Workup

  1. customA solution prepared
  2. additionwas added dropwise to this solution
  3. stirringThe reaction mixture was stirred at room temperature for 1 hour
  4. concentrationconcentrated under reduced pressure
  5. dissolutionthe residue was dissolved in a 9:1 mixed solvent of dichloromethane and methanol
  6. additionWater was added to the solution
  7. customliquid separation
  8. dry with materialThe resultant organic layer was dried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customthe residue was purified by column chromatography on silica gel (dichloromethane:methanol=100:3)
  11. customto obtain a colorless foamy substance
  12. concentrationthe suspension was concentrated under reduced pressure

Sources & evidence

ORD record
ord-fa682dbc7c2349cfb50319449ff687b1
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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