Methylamine → 2-(Methylamino)-1-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethanone

HRID 424573Notes

Reaction equation

[N+:1]([C:4]1[CH:13]=[CH:12][C:7]2[S:8][CH2:9][CH2:10][NH:11][C:6]=2[CH:5]=1)([O-:3])=[O:2].Cl[CH2:15][C:16](Cl)=[O:17].[CH3:19][NH2:20]>O1CCCC1.O.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:19][NH:20][CH2:15][C:16]([N:11]1[CH2:10][CH2:9][S:8][C:7]2[CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]1=2)=[O:17]

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of 6-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine (500 mg, 2.55 mmol) in tetrahydrofuran (4 mL) was added 2-chloroacetyl chloride (0.223 mL, 2.80 mmol). The resulting mixture was stirred at 60° C. for 10 minutes, at which time the reaction was cooled to 0° C. To the mixture was then added methylamine (2 M in tetrahydrofuran; 12.7 mL, 25.4 mmol). The resulting mixture was stirred at room temperature for 30 minutes. The mixture was then diluted with water and saturated sodium carbonate then extracted with dichloromethane (3×). The combined organics were dried, filtered, concentrated, and then chromatographed in 1:4:5 (2M NH3 in methanol:ethyl acetate:dichloromethane, giving the desired product (511 mg, 75%) as a yellow solid. 1H NMR (DMSO-d6) δ 8.36 (d, J=2.4 Hz, 1H), 7.93 (dd, J=8.7, 2.4 Hz, 1H), 7.50 (d, J=9.0 Hz, 1H), 3.93 (t, J=5.1 Hz, 2H), 3.48 (s, 2H), 3.34-3.28 (m, 2H), 2.28 (s, 3H), 2.00 (brs, 1H); ESI-MS (m/z, %): 268 (MH+, 100).

Workup

temperaturewas cooled to 0° C
stirringThe resulting mixture was stirred at room temperature for 30 minutes
extractionthen extracted with dichloromethane (3×)
customThe combined organics were dried
filtrationfiltered
concentrationconcentrated
customchromatographed in 1:4:5 (2M NH3 in methanol

Sources & evidence

ORD record: ord-b6694378a3984d15b31b9245c65de65d
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106043B2

Reaction notes

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