Formaldehyde → HCID 58438424, compound

HRID 401975Notes

Reaction equation

HRID 401975 reaction equation
Cl.Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[C:11]([C:26]([F:29])([F:28])[F:27])[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=O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C>C(Cl)Cl>[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:39])[CH2:33][CH2:32]2)=[C:11]([C:26]([F:28])([F:27])[F:29])[C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 2724942TriacetoxyborohydrideHCID 67373638HCID 67373638, compound

Product 1

HCID 58438424HCID 58438424, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-5-trifluoromethyl-pyridazine dihydrochloride (0.14 mmol, 0.075 g) and aqueous formaldehyde (37%, 0.68 mmol, 0.070 mL) in dry DCM (1.2 mL) was added macroporous resin-bound triacetoxyborohydride (loading 2.36 mmol/gram, 0.82 mmol, 0.35 g). The mixture was shaken for 12 hours. The reaction was filtered and the resin was washed with DCM (10 mL). The solvent was removed under reduced pressure. The crude product was purified on a 4 g SiO2 cartridge with 4-6% (2N NH3 in MeOH) in DCM to give 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(1-methyl-piperidin-4-yloxy)-5-trifluoromethyl-pyridazine. The neutral amine was treated with 2N HCl in diethyl ether (0.5 mL) and DCM (0.5 mL). The volatiles were removed under reduced pressure and the salt was triturated with diethyl ether and filtered to provide the title compound (0.05 g). LCMS: m/z 493 [M+1]; 1H NMR (400 MHz, CD3OD) δ 7.10-7.19 (2H, m), 7.00-7.09 (2H, d), 5.54-5.82 (1H, m), 4.38-4.43 (1H, m), 3.66 (1 h, d), 3.54 (1H, d), 3.10-3.35 (2H, m), 2.89-2.98 (3H, m), 2.64-2.73 (2H, m), 2.58 (1H, d), 2.46 (1H, d), 2.27 (1H, t), 1.96-2.13 (3H, m), 1.78-1.83 (2H, m), 1.14-1.66 (10H, m), 0.77 (3H, t).

Workup

  1. filtrationThe reaction was filtered
  2. washthe resin was washed with DCM (10 mL)
  3. customThe solvent was removed under reduced pressure
  4. customThe crude product was purified on a 4 g SiO2 cartridge with 4-6% (2N NH3 in MeOH) in DCM

Sources & evidence

ORD record
ord-eb807063c691449bb7b989d9f9f20947
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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