Hydrazine hydrate (1:1) → 4-(2-(Piperidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-amine

HRID 424511Notes

Reaction equation

[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:12]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[CH2:11][CH2:10][S:9][C:8]=2[CH:21]=1)([O-])=O.O.NN>CO.[Ni]>[N:15]1([CH2:14][CH2:13][N:12]2[CH2:11][CH2:10][S:9][C:8]3[CH:21]=[C:4]([NH2:1])[CH:5]=[CH:6][C:7]2=3)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 7-nitro-4-(2-(piperidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine (0.9 g, 2.93 mmol) in methanol (10 mL) under an argon atmosphere was treated first with hydrazine hydrate (1.424 mL, 29.3 mmol) and then with Raney-Nickel (˜0.172 g, 2.93 mmol). The reaction was transferred to oil bath pre-heated to 65° C. After one hour, the reaction mixture was poured over a pad of Celite. The pad of Celite was then rinsed with methanol (25 mL). The purple filtrate was concentrated and subjected to a short column on silica gel (1:9 (2M NH3 in MeOH):CH2Cl2). The fractions were concentrated, and the residue was carried on to the next step. 1H-NMR (DMSO-d6) δ 6.49 (d, J=8.7 Hz, 1H), 6.26-6.23 (m, 2H), 4.41 (s, 2H), 3.38-3.35 (m, 2H), 3.20 (t, J=7.2 Hz, 2H), 2.98-2.94 (m, 2H), 2.40-2.34 (m, 6H), 1.50-1.46 (m, 4H), 1.38-1.36 (m, 2H); ESI-MS (m/z, %): 278 (MH+, 100).

Workup

customThe reaction was transferred to oil bath
additionthe reaction mixture was poured over a pad of Celite
washThe pad of Celite was then rinsed with methanol (25 mL)
concentrationThe purple filtrate was concentrated
concentrationThe fractions were concentrated

Sources & evidence

ORD record: ord-edaaa060c9ce4b4085f3bee55d82237e
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106043B2

Reaction notes

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