Formaldehyde → HCID 57950316, compound

HRID 930765Notes

Reaction equation

HRID 930765 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:22]=[C:21]4[C:17]([C:18]5[CH2:27][CH2:26][NH:25][CH2:24][C:19]=5[N:20]4[CH3:23])=[CH:16][CH:15]=3)[C:10](=[O:28])[CH:9]=2)=[C:4]([O:29][CH3:30])[CH:3]=1.C=O.[C:33](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CO.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:22]=[C:21]4[C:17]([C:18]5[CH2:27][CH2:26][N:25]([CH3:33])[CH2:24][C:19]=5[N:20]4[CH3:23])=[CH:16][CH:15]=3)[C:10](=[O:28])[CH:9]=2)=[C:4]([O:29][CH3:30])[CH:3]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 52947270HCID 52947270, compound

Product 1

HCID 57950316HCID 57950316, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

4-(4-Chloro-2-methoxyphenyl)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one (83 mg, 0.20 mmol) and 37% aqueous formaldehyde (24 μL, 0.30 mmol) were dissolved in 1:1 MeOH/CH2Cl2 (1.4 mL) and stirred at room temperature for 45 min. Sodium triacetoxyborohydride (84 mg, 0.40 mmol) was added, and the reaction was stirred at ambient temperature for 30 min. The reaction mixture was neutralized with saturated NaHCO3 solution and extracted with CH2Cl2 (3×25 mL). The combined organics were washed with brine (25 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. Purification by flash column chromatography (12 g ISCO (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 95:5 to 10:90 over 20 column volumes, hold for 10 column volumes) provided the title compound (77 mg, 89%) as a yellow film: 1H NMR (500 MHz, CDCl3) δ 7.55 (d, J=8.0 Hz, 1H), 7.41 (d, J=7.0 Hz, 1H), 7.35-7.34 (m, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.07-7.03 (m, 2H), 7.00-6.99 (m, 1H), 6.81-6.80 (m, 1H), 6.43-6.42 (m, 1H), 3.87 (s, 3H), 3.66-3.65 (m, 2H), 3.48 (s, 3H), 2.87-2.86 (m, 2H), 2.81-2.80 (m, 2H), 2.58 (s, 3H).

Workup

  1. stirringthe reaction was stirred at ambient temperature for 30 min
  2. extractionextracted with CH2Cl2 (3×25 mL)
  3. washThe combined organics were washed with brine (25 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customPurification by flash column chromatography (12 g ISCO (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 95:5 to 10:90 over 20 column volumes, hold for 10 column volumes)

Sources & evidence

ORD record
ord-67f085dc35914af1a08f01cc0f1e043c
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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