Formaldehyde → HCID 58438375, compound

HRID 2168643Notes

Reaction equation

HRID 2168643 reaction equation
Cl.Cl.[CH2:3]([C:7]1[N:12]=[N:11][C:10]([O:13][CH2:14][CH:15]2[O:20][CH2:19][CH2:18][NH:17][CH2:16]2)=[CH:9][C:8]=1[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:23][CH:22]=1)[CH2:4][CH2:5][CH3:6].C=O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C>C(Cl)Cl>[CH2:3]([C:7]1[N:12]=[N:11][C:10]([O:13][CH2:14][CH:15]2[O:20][CH2:19][CH2:18][N:17]([CH3:36])[CH2:16]2)=[CH:9][C:8]=1[C:21]1[CH:22]=[CH:23][C:24]([O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:25][CH:26]=1)[CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 2724942TriacetoxyborohydrideHCID 67373189HCID 67373189, compound

Product 1

HCID 58438375HCID 58438375, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-morpholine dihydrochloride (0.067 mmol, 0.031 g) and aqueous formaldehyde (37%, 0.304 mmol, 0.025 mL) in dry DCM (2 mL) was added macroporous resin-bound triacetoxyborohydride (loading 2.36 mmol/gram, 0.364 mmol, 0.154 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 2-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-4-methyl-morpholine. 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 (0.022 g). LCMS: m/z 441 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.35-7.46 (3H, m), 7.09 (2H, d), 4.56-4.68 (2H, m), 4.38-4.47 (1H, m), 4.13-4.29 (2H, m), 3.91 (1H, t), 3.68 (1H, d), 3.49 (1H, d), 3.12-3.26 (2H, m), 3.00-3.09 (2H, m), 2.97 (3H, s), 1.99-2.02 (2H, m), 1.80-1.82 (2H, m), 1.19-1.66 (10H, m), 0.81 (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-e8859d32ccc84b3f8076a669ccaff0a8
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

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