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 902893Notes

Reaction equation

HRID 902893 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. After stirring for 1 hour, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a 9:1 mixed solvent of methylene chloride 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 (methylene chloride: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).

Workup

  1. customA solution prepared
  2. additionwas added dropwise to this solution
  3. stirringAfter stirring for 1 hour
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in a 9:1 mixed solvent of methylene chloride 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 (methylene chloride:methanol=100:3)
  11. customto obtain a colorless foamy substance
  12. concentrationthe suspension was concentrated under reduced pressure

Sources & evidence

ORD record
ord-3d08200413764df187a59860503ba2ac
Source dataset
uspto-grants-2008_04
Patent number
US07365205B2

Reaction notes

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