Formaldehyde → HCID 57950342, compound

HRID 1020701Notes

Reaction equation

HRID 1020701 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[C:16]([F:29])=[CH:17][C:18]3[C:19]4[CH2:28][NH:27][CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:30])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:35](C)=O.[Na+]>ClCCl.C(O)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[C:16]([F:29])=[CH:17][C:18]3[C:19]4[CH2:28][N:27]([CH3:35])[CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:30])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 57950399HCID 57950399, compound

Product 1

HCID 57950342HCID 57950342, compoundYield 71.9%

Reagents, catalysts & solvents 1

HCID 21922555Acetic acid methylene chlorideSolvent

Procedure

To a solution of 4-(benzyloxy)-1-(8-fluoro-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one (100 mg, 0.26 mmol) in dichloromethane/acetic acid (1% acetic acid, 10 mL) were sequentially added formaldehyde (37% aqueous solution, 22 μL, 0.74 mmol) and NaBH(OAc)3 (316 mg, 1.49 mmol). The reaction mixture was stirred at room temperature for 2.5 h. The mixture was concentrated under reduced pressure, and the residue was dissolved in CH2Cl2. The organic layer was washed with H2O and 5% aqueous LiCl, dried over Na2SO4, filtered and concentrated. Purification by flash chromatography (silica gel, CH2Cl2/(10:1:0.1 CH2Cl2/MeOH/NH4OH), 0:1 to 1:1) gave 4-(benzyloxy)-1-(8-fluoro-2,5-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one (78 mg, 38%) as a yellow solid. The free base was converted to the HCl salt using 1.25M HCl in methanol providing the title compound (75 mg, 95%) as a off-white solid: 1H NMR (300 MHz, CD3OD) δ 7.53-7.33 (m, 7H), 7.27 (d, J=10.5 Hz, 1H), 7.28 (dd, J=7.8, 2.4 Hz, 1H), 6.10 (d, J=2.7 Hz, 1H), 5.17 (s, 2H), 3.79 (br s, 2H), 3.67 (s, 3H), 3.03-3.00 (m, 4H), 2.64 (s, 3H); ESI MS m/z 418 [M+H]+; HPLC (Method A) 95.7% (AUC), tR=14.5 min.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in CH2Cl2
  3. washThe organic layer was washed with H2O and 5% aqueous LiCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography (silica gel, CH2Cl2/(10:1:0.1 CH2Cl2/MeOH/NH4OH), 0:1 to 1:1)

Sources & evidence

ORD record
ord-39d69ba99f8d45ddb15267e5c5451720
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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