Formaldehyde → (R)-4-((1-methylpiperidin-2-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60305Notes

Reaction equation

HRID 60305 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C@@H:2]1[CH2:7][O:8][C:9]1[C:17]2[C:16]3[CH:18]=[C:19]([C:22]#[N:23])[N:20]=[CH:21][C:15]=3[N:14]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:13]=2[N:12]=[CH:11][CH:10]=1.C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C.O.C(=O)(O)[O-].[Na+].C(Cl)Cl>[CH3:34][N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C@@H:2]1[CH2:7][O:8][C:9]1[C:17]2[C:16]3[CH:18]=[C:19]([C:22]#[N:23])[N:20]=[CH:21][C:15]=3[N:14]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:13]=2[N:12]=[CH:11][CH:10]=1

Participants

8

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58365030(R)-4-(piperidin-2-ylmethoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 67249073(R)-4-((1-methylpiperidin-2-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (R)-4-(piperidin-2-ylmethoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (220 mg, 0.50 mmol) in acetonitrile (2.2 mL) and water (0.45 mL) was added Formalin (41 uL, 1.5 mmol) followed by sodium triacetoxyborohydride (210 mg, 1.0 mmol), and the reaction mixture was stirred at ambient temperature for 20 minutes. The mixture diluted with saturated aqueous sodium bicarbonate solution (50 mL) and methylene chloride (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified flash chromatography (silica, 4 g, ISCO, 1-20% methanol in methylene chloride) to afford the title compound as a yellow solid, which was used in the next step without any further purification (197 mg, 87%).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified flash chromatography (silica, 4 g, ISCO, 1-20% methanol in methylene chloride)

Sources & evidence

ORD record
ord-7364bca3d9bd48369f0bdd677da07ff0
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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