Formaldehyde → HCID 44194483, compound

HRID 1020659Notes

Reaction equation

HRID 1020659 reaction equation
Cl.[CH:2]1([CH2:8][O:9][C:10]2[CH:15]=[CH:14][N:13]([C:16]3[CH:17]=[CH:18][C:19]4[C:20]5[CH2:29][NH:28][CH2:27][CH2:26][C:21]=5[N:22]([CH3:25])[C:23]=4[CH:24]=3)[C:12](=[O:30])[CH:11]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH2:31](N(CC)CC)C.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO>[CH:2]1([CH2:8][O:9][C:10]2[CH:15]=[CH:14][N:13]([C:16]3[CH:17]=[CH:18][C:19]4[C:20]5[CH2:29][N:28]([CH3:31])[CH2:27][CH2:26][C:21]=5[N:22]([CH3:25])[C:23]=4[CH:24]=3)[C:12](=[O:30])[CH:11]=2)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 68657025HCID 68657025, compound

Product 1

HCID 44194483HCID 44194483, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-(cyclohexylmethoxy)-1-(5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one hydrochloride (110 mg, 0.26 mmol) in CH3OH (5 mL) was added triethylamine (90 μL, 2.5 mmol), formaldehyde (30 μL, 0.39 mmol) and NaBH(OAc)3 (110 mg, 0.52 mmol). The reaction was stirred at room temperature until complete. The solvent was removed under reduced pressure, and the residue was dissolved in CH2Cl2. The organic solution was washed with H2O and 5% aqueous LiCl and dried over Na2SO4. After filtration and concentration, the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give 4-(cyclohexylmethoxy)-1-(2,5-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one as a white solid (73 mg, 69%). The free base was converted to the HCl salt to give the title compound (84 mg, 100%) as a white powder: mp 270-272° C.; 1H NMR (500 MHz, DMSO-d6) δ 10.53 (s, 1H), 7.53 (d, J=7.5 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.50 (d, J=1.5 Hz, 1H), 7.00 (dd, J=8.5, 1.5 Hz, 1H), 6.04 (dd, J=7.5, 2.5 Hz, 1H), 5.85 (d, J=3.0 Hz, 1H), 4.64 (d, J=13 Hz, 1H), 4.30 (dd, J=14, 7.5 Hz, 1H), 3.82 (d, J=6.0 Hz, 2H), 3.80-3.78 (m, 1H), 3.69 (s, 3H), 3.51-3.47 (m, 1H), 3.18 (t, J=5.5 Hz, 2H), 2.98 (d, J=4.5 Hz, 3H), 1.80-1.65 (m, 6H), 1.30-1.01 (m, 5H); ESI MS m/z 406 [M+H]+; HPLC (Method A)>99% (AUC), tR=14.4 min.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in CH2Cl2
  3. washThe organic solution was washed with H2O and 5% aqueous LiCl
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-442626a9900f4cf19547a6b65a4de38b
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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