3,4-Dichloro-1,2,5-thiadiazole → [1-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl ester

HRID 907539

Reaction equation

[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[C:21](Cl)=[N:20][S:19][N:18]=1.CCN(C(C)C)C(C)C>CN(C=O)C.Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH:10]1[CH2:11][CH2:12][N:13]([C:21]2[C:17]([Cl:16])=[N:18][S:19][N:20]=2)[CH2:14][CH2:15]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 100 °C

Procedure

4-(tert-Butoxycarbonylaminomethyl)piperidine (3.96 g, 18.4 mmol) was dissolved in DMF (3.5 ml) and heated to 100° C. 3,4-Dichloro-1,2,5-thiadiazole (0.85 mL, 9.0 mmol) was added and the mixture stirred at 100° C. overnight. DIEA (2.0 ml, 11.5 mmol) was added and heating at 100° C. continued until the reaction was complete (˜3 h). The reaction mixture was diluted with 1N HCl and extracted with EtOAc (3×). The combined EtOAc extractions were washed with H2O (1×), sat'd NaCl (1×), dried (MgSO4), and concentrated in vacuo to give 2.39 g (80%) of [1-(4-chloro-[1,2,5]thiadiazol-3-yl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl ester as a tan solid. 1H NMR (DMSO-d6) 6.91 (t, 1H), 3.87 (m, 2H), 2.84 (m, 4H), 1.69 (m, 2H), 1.56 (m, 1H), 1.36 (s, 9H), 1.24 (m, 2H) ppm. LC-MS (MH+)=333.

Workup

temperatureheating at 100° C.
custom(˜3 h)
extractionextracted with EtOAc (3×)
extractionThe combined EtOAc extractions
washwere washed with H2O (1×), sat'd NaCl (1×)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-1f06c276b2cb4980b3f96dae211fc190
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08013156B2

Linked notes

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