Formaldehyde → HCID 57950345, compound

HRID 930735Notes

Reaction equation

HRID 930735 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][N:13]([C:16]2[CH:24]=[C:23]3[C:19]([C:20]4[CH2:29][CH2:28][NH:27][CH:26]([CH3:30])[C:21]=4[N:22]3[CH3:25])=[CH:18][CH:17]=2)[C:12](=[O:31])[CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:36](C)=O.[Na+]>CO>[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][N:13]([C:16]2[CH:24]=[C:23]3[C:19]([C:20]4[CH2:29][CH2:28][N:27]([CH3:36])[CH:26]([CH3:30])[C:21]=4[N:22]3[CH3:25])=[CH:18][CH:17]=2)[C:12](=[O:31])[CH:11]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68658134HCID 68658134, compound

Product 1

HCID 57950345HCID 57950345, compoundYield 77.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-(benzyloxy)-1-(1,9-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride (205 mg, 0.470 mmol) in CH3OH (8 mL) was added formaldehyde (53 μL, 0.71 mmol) and NaBH(OAc)3 (200 mg, 0.94 mmol). The reaction was stirred at room temperature until complete and then concentrated under reduced pressure. The residue was dissolved in CH2Cl2 and washed with H2O and 5% aqueous LiCl and dried over Na2SO4. The organic solution was filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give 4-(benzyloxy)-1-(1,2,9-trimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one as a white solid (0.15 g, 77%). The free base was converted to the HCl salt to give the title compound (147 mg, 90%) as an off-white powder: 1H NMR (500 MHz, CD3OD) δ 7.58-7.55 (m, 2H), 7.47-7.34 (m, 6H), 6.99 (d, J=8.5, 1.0 Hz, 1H), 6.28 (dd, J=7.5, 2.5 Hz, 1H), 6.11 (d, J=2.5 Hz, 1H), 5.18 (s, 2H), 4.27 (q, J=6.5 Hz, 1H), 3.69 (s, 3H), 3.36-3.33 (m, 1H), 3.10-2.96 (m, 2H), 2.84-2.80 (m, 1H), 2.65 (s, 3H), 1.51 (d, J=6.5 Hz, 3H); ESI MS m/z 414 [M+H]+; HPLC (Method A)>99% (AUC), tR=13.0 min.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in CH2Cl2
  3. washwashed with H2O and 5% aqueous LiCl
  4. dry with materialdried over Na2SO4
  5. filtrationThe organic solution was filtered
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-c9916a7e10cf4eaca6897504318bf5bf
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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