Hydrochloric Acid → HCID 67373738, compound

HRID 2168697Notes

Reaction equation

HRID 2168697 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:27][CH:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:15][CH:14]=1)[CH2:4][CH2:5][CH3:6].[C:35]([Cl:38])(=[O:37])[CH3:36].CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOCC>[ClH:38].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:27][CH:28]2[CH2:29][CH2:30][N:31]([CH3:34])[CH2:32][CH2:33]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][N:24]([C:35](=[O:37])[CH3:36])[CH2:23][CH2:22]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 67373335HCID 67373335, compound

Product 1

HCID 67373738HCID 67373738, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-butyl-6-(1-methyl-piperidin-4-yloxy)-4-[4-(piperidin-4-ylmethoxy)-phenyl]-pyridazine dihydrochloride (0.2 mmol, 103 mg) in DCM (1 mL) at 0° C. was added acetyl chloride (0.4 mmol, 29 μL), DIEA (0.4 mmol, 70 μL) and DMAP (5 mg). The mixture was stirred at room temperature for 1 hour. The mixture was then condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound. LCMS: m/z 482 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.63 and 7.75 (1 H, s), 7.44-7.50 (2 H, m), 7.12-7.17 (2 H, m), 5.37-5.54 (1 H, m), 4.37 (2 H, d), 3.36-3.69 (3 H, m), 3.08-3.30 (4 H, m), 2.92 (3 H, s), 2.11-2.74 (5 H, m), 2.10 (3 H, s), 1.86-2.08 (4 H, m), 1.25-1.54 (7 H, m), 0.82 (3 H, t).

Workup

  1. customcondensed in vacuo
  2. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  3. customto give a colorless sticky solid, which
  4. waitkept at room temperature for 10 min
  5. customcondensed
  6. customtriturated with hexanes

Sources & evidence

ORD record
ord-fa3dee63ba974a7da19389c2768793b9
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

Loading…