Tetrahydrofuran → Methyl 2-[2-{[((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)amino]carbonyl}-6,7-dihydrothiazolo[5,4-c]pyridin-5(4H)-yl]ethylcarbamate Hydrochloride

HRID 2104444Notes

Reaction equation

HRID 2104444 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:48])[O:46][CH3:44])[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 67056490Methyl 2-[2-{[((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)amino]carbonyl}-6,7-dihydrothiazolo[5,4-c]pyridin-5(4H)-yl]ethylcarbamate HydrochlorideYield 75.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

The compound (144 mg) obtained in Example 40 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 at room temperature. After stirring for 1 hour, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a 9:1 mixture of methylene chloride and methanol. Water was added to the solution for partitioning the mixture. The organic layer was separated and dried over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride:methanol=100:3) to give a colorless foamy substance. This product was suspended in 1N hydrochloric acid (0.2 mL), and the suspension was concentrated under reduced pressure to give the title compound (60 mg).

Workup

  1. customA solution prepared
  2. additionwas added dropwise to this solution at room temperature
  3. stirringAfter stirring for 1 hour
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in a 9:1 mixture of methylene chloride and methanol
  6. additionWater was added to the solution
  7. customfor partitioning the mixture
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate anhydrate
  10. distillationThe solvent was distilled away under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (methylene chloride:methanol=100:3)
  12. customto give a colorless foamy substance
  13. concentrationthe suspension was concentrated under reduced pressure

Sources & evidence

ORD record
ord-94e4fa938178484197991c6417ba14ff
Source dataset
uspto-grants-2009_08
Patent number
US07576135B2

Reaction notes

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