Formaldehyde → HCID 58438384, compound

HRID 1971918Notes

Reaction equation

HRID 1971918 reaction equation
Cl.Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH2:27][CH2:28][C@H:29]2[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]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=O.[C:37](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:26][CH2:27][CH2:28][C@H:29]2[CH2:34][CH2:33][CH2:32][CH2:31][N:30]2[CH3:37])=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 2724942TriacetoxyborohydrideHCID 67374143HCID 67374143, compound

Product 1

HCID 58438384HCID 58438384, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-((R)-2-piperidin-2-yl-ethoxy)-pyridazine dihydrochloride (0.065 mmol, 0.033 g) and aqueous formaldehyde (37%, 0.323 mmol, 0.03 mL) in dry DCM (2 mL) was added macroporous resin-bound triacetoxyborohydride (loading 2.36 mmol/gram, 0.39 mmol, 0.165 g). The mixture was shaken for 12 hours. The reaction was filtered and the resin was washed with DCM (5 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-[2-((R)-1-methyl-piperidin-2-yl)-ethoxy]-pyridazine (0.02 g, 73%). The neutral amine was treated with 2N HCl in diethyl ether (1 mL) and DCM (1 mL). The volatiles were removed under reduced pressure and the salt was triturated with diethyl ether and filtered to provide the title compound (0.025 g). LCMS: m/z 453 [M+1]. 1H NMR (400 MHz, CD3OD) δ 6.97-7.45 (5H, m), 4.55-4.72 (2H, m), 4.35-4.46 (1H, m), 3.46-3.82 (1H, m), 3.05-3.19 (1H, m), 2.79-3.06 (5H, m), 2.44-2.74 (2H, m), 2.10-2.36 (2H, m), 1.74-2.06 (9H, m), 0.79 (3H, t).

Workup

  1. filtrationThe reaction was filtered
  2. washthe resin was washed with DCM (5 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-a0baad37a2164093b92ee5a383a7578a
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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