Hydrochloric Acid → HCID 178484223, compound

HRID 424576Notes

Reaction equation

[CH3:1][N:2]([CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][S:15][C:14]2[CH:18]=[CH:19][C:20]([NH:22][C:23]([C:25]3[S:26][CH:27]=[CH:28][CH:29]=3)=[NH:24])=[CH:21][C:13]1=2)C(=O)OC(C)(C)C.Cl.[OH-].[Na+]>CO.O>[CH3:1][NH:2][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][S:15][C:14]2[CH:18]=[CH:19][C:20]([NH:22][C:23]([C:25]3[S:26][CH:27]=[CH:28][CH:29]=3)=[NH:24])=[CH:21][C:13]1=2

Participants

Conditions

Temperature: 90 °C

Procedure

To a stirred solution of tert-butyl methyl(2-(6-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)carbamate (415 mg, 0.959 mmol) in methanol (4 mL) was added a 3N HCl solution (3.198 mL, 9.59 mmol). The resulting mixture was then stirred at 90° C. for 1 hour. The mixture was then cooled to room temperature, diluted with water, basified with 3N sodium hydroxide to pH 12, and extracted with dichloromethane (3×). The combined organics were dried, filtered, and concentrated then chromatographed in 1:9 (2M NH3 in methanol):ethyl acetate, giving the desired product 28 (165 mg, 51.7%). 1H NMR (DMSO-d6) δ 7.71 (d, J=3.0 Hz, 1H), 7.58 (d, J=5.1 Hz, 1H), 7.10-7.06 (m, 1H), 6.82 (d, J=8.1 Hz, 1H), 6.34 (brs, 2H), 6.22 (s, 1H), 6.07 (d, J=8.1 Hz, 1H), 3.62-3.57 (m, 2H), 3.32 (t, J=6.8 Hz, 2H), 3.01-2.97 (m, 2H), 2.64 (t, J=6.8 Hz, 1H), 2.29 (s, 3H). ESI-MS (m/z, %): 333 (MH+, 100), 276 (71); ESI-HRMS calculated for C16H21N4S2 (MH+), calculated: 333.1202, observed: 333.1207; HPLC purity: 97% by area.

Workup

temperatureThe mixture was then cooled to room temperature
extractionextracted with dichloromethane (3×)
customThe combined organics were dried
filtrationfiltered
concentrationconcentrated
customthen chromatographed in 1:9 (2M NH3 in methanol)

Sources & evidence

ORD record: ord-edd0d62a4eb0470483661368090bd66d
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106043B2

Reaction notes

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