Hydrochloric Acid → HCID 67373658, compound

HRID 1971904Notes

Reaction equation

HRID 1971904 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1)[CH2:4][CH2:5][CH3:6].[C:33]([O:37][CH2:38][CH3:39])(=[O:36])[CH:34]=[CH2:35].CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:38]([O:37][C:33](=[O:36])[CH2:34][CH2:35][N:30]1[CH2:31][CH2:32][CH:27]([O:26][C:10]2[N:9]=[N:8][C:7]([CH2:3][CH2:4][CH2:5][CH3:6])=[C:12]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)=[CH:17][CH:18]=3)[CH:11]=2)[CH2:28][CH2:29]1)[CH3:39]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8821Ethyl AcrylateHCID 81531DiisopropylethylamineHCID 67375293HCID 67375293, compound

Product 1

HCID 67373658HCID 67373658, compoundYield 135.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (Example 14, 2.0 mmol, 965 mg) in DCM (5 mL) was added ethyl acrylate (6.0 mmol, 0.66 mL), and DIEA (6.0 mmol, 1.05 mL). The mixture was stirred at room temperature over night then condensed. 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 (2.0 mL), 2N HCl in ether (2.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (792 mg). LCMS: m/z 512 [M+2]. 1H NMR (400 MHz, CD3OD): δ 7.30-7.34 (2H, m), 7.01-7.07 (3H, m), 5.47-5.53 (1H, m), 4.37-4.43 (1H, m), 4.20 (2H, q), 3.35-3.70 (5H, m), 2.87-2.95 (5H, m), 2.20-2.35 (4H, m), 1.96-2.03 (2H, m), 1.78-1.84 (2H, m), 1.35-1.64 (7H, m), 1.28 (3H, t), 1.20-1.26 (3H, m), 0.80 (3H, t).

Workup

  1. customcondensed
  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. customcondensed
  5. customtriturated with hexanes

Sources & evidence

ORD record
ord-72275d252eee4d4983c85d01543564e4
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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