Hydrochloric Acid → HCID 67387040, compound

HRID 1972041Notes

Reaction equation

HRID 1972041 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:17]([NH:19][C:20](=[O:22])C)[CH:18]=1)[CH2:4][CH2:5][CH3:6].[C:38]([N:42]=C=O)([CH3:41])([CH3:40])[CH3:39].Cl>C1COCC1.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[C:38]([NH:42][C:20]([NH:19][C:17]1[CH:18]=[C:13]([C:12]2[CH:11]=[C:10]([O:30][CH:31]3[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]3)[N:9]=[N:8][C:7]=2[CH2:3][CH2:4][CH2:5][CH3:6])[CH:14]=[CH:15][C:16]=1[O:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)=[O:22])([CH3:41])([CH3:40])[CH3:39]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 62412tert-Butyl isocyanateHCID 67373992HCID 67373992, compound

Product 1

HCID 67387040HCID 67387040, compoundYield 126.4%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-phenylamine (Example 62, 0.5 mmol, 219 mg) in dry THF (1.0 mL) was added tert-butyl isocyanate (1.5 mmol, 149 mg), and the mixture was stirred at room temperature over night. It 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 (5.0 mL), 2N HCl in ether (5.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (193 mg). LCMS: m/z 539 [M+1]. 1H NMR (400 MHz, CD3OD): δ 8.09-8.12 (1H, m), 7.55 and 7.65 (1H, s), 7.12-7.18 (1H, m), 7.00-7.08 (1H, m), 5.36-5.56 (1H, m), 4.41-4.48 (1H, m), 3.25-3.67 (4H, m), 3.08-3.15 (2H, m), 2.93 (3H, s), 2.02-2.58 (6H, m), 1.83-1.89 (2H, m), 1.40-1.70 (8H, m), 1.38 (9H, s), 1.26-1.36 (2H, m), 0.83 (3H, 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. customcondensed
  5. customtriturated with hexanes

Sources & evidence

ORD record
ord-852e1b949d044efd8d1cf0ae01df5d9d
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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