Lithium Hydroxide → (1S,2R,4R)-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo [5,4-c]pyridin-2-yl)carbonyl]-4-(piperidin-1-yl)carbonyl-1,2-cyclohexanediamine hydrochloride

HRID 546539Notes

Reaction equation

HRID 546539 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]([NH:13][C@H:14]1[CH2:19][CH2:18][C@@H:17]([C:20](OC)=[O:21])[CH2:16][C@H:15]1[NH:24][C:25]([C:27]1[S:28][C:29]3[CH2:30][N:31]([CH3:36])[CH2:32][CH2:33][C:34]=3[N:35]=1)=[O:26])=[O:12])=[CH:5]2.[OH-].[Li+]>O1CCCC1.O>[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:13][C@H:14]1[CH2:19][CH2:18][C@@H:17]([C:20]([N:31]3[CH2:32][CH2:33][CH2:34][CH2:29][CH2:30]3)=[O:21])[CH2:16][C@H:15]1[NH:24][C:25]([C:27]1[S:28][C:29]3[CH2:30][N:31]([CH3:36])[CH2:32][CH2:33][C:34]=3[N:35]=1)=[O:26])=[O:12])=[CH:5]2

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 9984457HCID 9984457, compound

Product 1

HCID 68908004(1S,2R,4R)-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo [5,4-c]pyridin-2-yl)carbonyl]-4-(piperidin-1-yl)carbonyl-1,2-cyclohexanediamine hydrochlorideYield 112.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(1S,2R,4R)—N1-[(5-Chloroindol-2-yl)carbonyl]-4-methoxycarbonyl-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine (200 mg) was dissolved in tetrahydrofuran (5 ml) and water (0.6 ml), and lithium hydroxide (12 mg) was added to stir the mixture at room temperature. After 3 hours, the reaction was stopped, the solvent was concentrated under reduced pressure, and the residue was then dissolved in N,N-dimethylformamide (10 ml), to which piperidine (65 mg), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (110 mg), 1-hydroxybenzotriazole (77 mg) and diisopropylethylamine (390 mg) were added, and the mixture was stirred at room temperature for 3 days. The solvent was distilled off under reduced pressure, dichloromethane was added to the residue, and the resultant mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate. The resultant organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resultant residue was purified by column chromatography on silica gel (methanol:dichloromethane=1:10) to obtain a product (132 mg) in a free form. This product was dissolved in methanol, to which 1N ethanol solution (230 μl) of hydrochloric acid was added. The mixture was dried to solid. Ether was added to the residue to solidify it. This solid was collected by filtration to obtain the title compound (127 mg) as a colorless solid.

Workup

  1. concentrationthe solvent was concentrated under reduced pressure
  2. dissolutionthe residue was then dissolved in N,N-dimethylformamide (10 ml), to which piperidine (65 mg), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (110 mg), 1-hydroxybenzotriazole (77 mg) and diisopropylethylamine (390 mg)
  3. additionwere added
  4. stirringthe mixture was stirred at room temperature for 3 days
  5. distillationThe solvent was distilled off under reduced pressure, dichloromethane
  6. additionwas added to the residue
  7. washthe resultant mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate
  8. dry with materialThe resultant organic layer was dried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customthe resultant residue was purified by column chromatography on silica gel (methanol:dichloromethane=1:10)

Sources & evidence

ORD record
ord-82471577edf04239809df9aba019019e
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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