Hydrochloric Acid → ethyl (1S)-1-{5-[1-methyl-4-(4-{(3-methylpyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl)-1H-pyrazol-5-yl]-2H-tetrazol-2-yl}ethyl carbonate

HRID 588400Notes

Reaction equation

[CH2:1]([O:3][C:4]([O:6][C@H:7]([N:9]1[N:13]=[N:12][C:11]([C:14]2[N:18]([CH3:19])[N:17]=[CH:16][C:15]=2[C:20]2[CH:48]=[CH:47][C:23]([C:24]([N:26]([C:40]3[C:45]([CH3:46])=[CH:44][CH:43]=[CH:42][N:41]=3)[C@@H:27]3[CH2:32][CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28]3)=[O:25])=[CH:22][CH:21]=2)=[N:10]1)[CH3:8])=[O:5])[CH3:2].Cl.O1CCOCC1>C(#N)C>[C:4](=[O:5])([O:6][C@H:7]([N:9]1[N:13]=[N:12][C:11]([C:14]2[N:18]([CH3:19])[N:17]=[CH:16][C:15]=2[C:20]2[CH:48]=[CH:47][C:23]([C:24](=[O:25])[N:26]([C:40]3[C:45]([CH3:46])=[CH:44][CH:43]=[CH:42][N:41]=3)[C@@H:27]3[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]3)=[CH:22][CH:21]=2)=[N:10]1)[CH3:8])[O:3][CH2:1][CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

Preparation 27, tert-butyl (3R)-3-[{4-[5-(2-{(1S)-1-[(ethoxycarbonyl)oxy]ethyl}-2H-tetrazol-5-yl)-1-methyl-1H-pyrazol-4-yl]benzoyl}(3-methylpyridin-2-yl)amino]piperidine-1-carboxylate (438 mg, 0.664 mmol) was dissolved in acetonitrile (3.3 mL). To this was added HCl in dioxane (2.49 mL, 4M solution, 15 eq.) dropwise at room temperature. After 1 h, the reaction was concentrated in vacuo, and concentrated with toluene (3×15 mL). The crude material was suspended in EtOAc and heated to 80° C. for 16 h. Filtration of the material provided the hydrochloride salt of ethyl (1S)-1-{5-[1-methyl-4-(4-{(3-methylpyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl)-1H-pyrazol-5-yl]-2H-tetrazol-2-yl}ethyl carbonate (242 mg, 65%).

Workup

concentrationthe reaction was concentrated in vacuo
concentrationconcentrated with toluene (3×15 mL)
filtrationFiltration of the material

Sources & evidence

ORD record: ord-f8d7f09a80ed4ade81858c2c354caa2b
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227956B2

Reaction notes

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