Sulfuric Acid → HCID 87439752, compound

HRID 2176116Notes

Reaction equation

HRID 2176116 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)N)=[CH:4][N:3]=1.[CH3:19][NH+:20]1[C@@H:25]2[CH2:26][C:27]([CH2:29][C@H:21]1[CH2:22][CH2:23][CH2:24]2)=O.S(=O)(=O)(O)O>O1CCOCC1>[CH3:18][C:15]1[CH:14]=[C:13]2[C:12](=[CH:17][CH:16]=1)[N:10]([CH2:9][CH2:8][C:5]1[CH:4]=[N:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C:23]1[CH2:24][CH:25]3[N:20]([CH3:19])[CH:21]([C:22]2=1)[CH2:29][CH2:27][CH2:26]3

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 11877144HCID 11877144, compoundHCID 86640695HCID 86640695, compound

Product 1

HCID 87439752HCID 87439752, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 25 ml, round-bottomed flask were combined 2-chloro-5-(2-(1-p-tolylhydrazinyl)-ethyl)pyridine (50 mg, 0.19 mmol; Example 117D), pseudopelletierine hydrochloride (40 g, 0.21 mmol; Acros), and concentrated sulfuric acid (31 μL) in dioxane (8 mL). The reaction mixture was heated to 80° C. for 6 hours, then cooled to room temperature. The solvent was removed under vacuum and residue was purified by reverse-phase HPLC [Waters XBridge™ C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1% trifluoroacetic acid) over 15 minutes] to afford the title compound as the bistrifluoroacetic acid salt: 1H NMR (300 MHz, methanol-d4) δ ppm 0.94-1.13 (m, 1H), 1.39-1.51 (m, 1H), 1.71-1.80 (m, 1H), 1.91-2.17 (m, 3H), 2.43 (s, 3H), 2.50 (d, J=18 Hz, 1H), 2.66 (s, 3H), 2.96 (dd, J=18, 7 Hz, 1H), 3.14-3.23 (m, 2H), 3.83 (t, J=5 Hz, 1H), 4.41 (t, J=6 Hz, 2H), 4.90 (d, J=2 Hz, 1H), 7.09 (d, J=8 Hz, 1H), 7.24 (s, 1H), 7.32 (d, J=8 Hz, 1H), 7.37 (d, J=8 Hz, 1H), 7.50 (dd, J=8, 2 Hz, 1H), 7.77 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 380 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed under vacuum and residue
  3. customwas purified by reverse-phase HPLC [Waters XBridge™ C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1% trifluoroacetic acid) over 15 minutes]

Sources & evidence

ORD record
ord-1b649130abe245ee954270dfe5f084c3
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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