Ammonium Chloride → 2-(8-Fluoro-2-(3-formyl-4-iodopyridin-2-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile

HRID 337323Notes

Reaction equation

HRID 337323 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:13]([CH3:17])([CH3:16])[C:14]#[N:15])[CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH:8]=[CH:7]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:29]1[N:36]=[CH:35][CH:34]=[C:33]([I:37])[C:30]=1[CH:31]=[O:32].[NH4+].[Cl-]>O.C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:13]([CH3:17])([CH3:16])[C:14]#[N:15])[CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:29]1[C:30]([CH:31]=[O:32])=[C:33]([I:37])[CH:34]=[CH:35][N:36]=1)[CH:8]=[CH:7]2

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 99923282-Fluoro-4-iodopyridine-3-carbaldehydeHCID 667426112-(8-Fluoro-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile

Product 1

HCID 866769382-(8-Fluoro-2-(3-formyl-4-iodopyridin-2-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrileYield 51.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a 100 mL round-bottomed flask 2-(8-fluoro-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile (800 mg, 3.47 mmol, 1 equiv.) was combined with THF (32.0 ml) to give a yellow suspension. A solution of lithium bis(trimethylsilyl)amide in THF 1M (4.52 ml, 4.52 mmol, 1.3 equiv.) was added. The reaction mixture was stirred at room temperature for 15 min. To the resultant amber solution was added 2-fluoro-4-iodonicotinaldehyde (1.31 g, 5.21 mmol, 1.5 equiv.). The reaction mixture was heated at 50° C. with stirring for 15 h. The reaction mixture was poured into 5 mL saturated NH4Cl and 100 mL H2O and extracted with DCM (3×100 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0%, then 0% to 0.5% MeOH in DCM), followed by trituration with ether:hexanes (1:8) to afford 2-[8-fluoro -2-(3-formyl-4-iodo-pyridin-2-yl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-2-methyl-propionitrile as a pale yellow solid (830 mg). (M+H)+=462 m/e.

Workup

  1. customto give a yellow suspension
  2. temperatureThe reaction mixture was heated at 50° C.
  3. stirringwith stirring for 15 h
  4. extractionextracted with DCM (3×100 mL)
  5. dry with materialThe organic layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 80 g, 0%

Sources & evidence

ORD record
ord-006902b0ea5040e8b771ec444f196d50
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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