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

HRID 424541Notes

Reaction equation

HRID 424541 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:12]([CH2:13][CH2:14][CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:11][CH2:10][S:9][C:8]=2[CH:21]=1)([O-])=O.O.NN>CO.[Ni]>[N:16]1([CH2:15][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]1

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 591441447-Nitro-4-(3-(pyrrolidin-1-yl)propyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine

Product 1

HCID 591440974-(3-(Pyrrolidin-1-yl)propyl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-amineYield 91%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

A solution of 7-nitro-4-(3-(pyrrolidin-1-yl)propyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine (0.55 g, 1.789 mmol) in dry methanol (10 mL) was treated with hydrazine hydrate (0.652 mL, 17.89 mmol) followed by Raney-Nickel (0.1 g, 1.789 mmol) at room temperature. The resulting mixture was stirred at reflux for 5 minutes using a pre-heated oil bath. The reaction was then brought to room temperature, filtered through a pad of Celite, and washed with methanol (3×10 mL). The combined methanol layers were evaporated, and the crude material was purified by flash column chromatography (5:95 (2 M NH3 in MeOH):CH2Cl2) to obtain the title product (0.45 g, 91%) as a syrup. 1H NMR (DMSO-d6) δ 6.51 (d, 1H, J=9.3 Hz), 6.26-6.23 (m, 2H), 4.41 (s, 2H), 3.37-3.30 (m, 2H, merged with water peak), 3.11 (t, 2H, J=6.9 Hz), 2.98-2.95 (m, 2H), 2.42-2.37 (m, 6H), 1.67-1.60 (m, 6H).

Workup

  1. temperatureat reflux for 5 minutes
  2. customwas then brought to room temperature
  3. filtrationfiltered through a pad of Celite
  4. washwashed with methanol (3×10 mL)
  5. customThe combined methanol layers were evaporated
  6. customthe crude material was purified by flash column chromatography (5:95 (2 M NH3 in MeOH):CH2Cl2)

Sources & evidence

ORD record
ord-2cf7eddd772048e98c07fd1c8d46bde2
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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