Diethyl (cyanomethyl)phosphonate → HCID 24812116, compound

HRID 1879666Notes

Reaction equation

HRID 1879666 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[Na].C(OP([CH2:19][C:20]#[N:21])(=O)OCC)C.[CH3:22][N:23]1[CH2:29][CH2:28][CH2:27][N:26]([C:30]2[N:35]=[C:34]([C:36]3[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=3)[CH:39]=O)[CH:33]=[N:32][CH:31]=2)[CH2:25][CH2:24]1>C1COCC1>[CH3:22][N:23]1[CH2:29][CH2:28][CH2:27][N:26]([C:30]2[N:35]=[C:34]([C:36]3[CH:37]=[C:38](/[CH:39]=[CH:19]/[C:20]#[N:21])[CH:41]=[CH:42][CH:43]=3)[CH:33]=[N:32][CH:31]=2)[CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 45051731Sodium hexamethyidisilazaneHCID 59447701HCID 59447701, compound

Product 1

HCID 24812116HCID 24812116, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(6-Chloro-pyrazin-2-yl)-4-methyl-[1,4] diazepane (360 mg, 1.59 mmol), (intermediate C prepared in example 3), 3-formylphenylboronic acid (235 mg, 1.58 mmol) and bistriphenylphosphinepalladium(II)chloride (21 mg, 0.03 mmol) were dispersed in 10 mL DMF in a reaction tube. Subsequently 1.5 mL of 2M Na2CO3 was added. The tube was sealed and the reaction mixture was heated at 90° C. for 3 hours. The reaction mixture was then filtered through a plug of celite, diluted with ethyl acetate and water (25 mL), and the organic phase was separated. The aqueous phase was extracted with 2×10 mL ethyl acetate. The organic extracts were combined, washed with brine, dried and concentrated. The residue was purified by flash chromatography. Intermediate L (337 mg, 72%; MS analysis electrospray, 297, M+H) was isolated by concentration of the solvents and used directly. Sodium hexamethyldisilazane (0.22 mL, 1M in THF, 0.22 mmol) was added to a solution of cyanomethyl-phosphonic acid diethyl ester (0.034 mL, 0.21 mmol) in 1 mL THF under an atmosphere of N2. The mixture was stirred for 2 h after which time a solution of 3-[6-(4-methyl-[1,4] diazepan-1-yl)-pyrazin-2-yl]-benzaldehyde in 2 mL THF was added. After 15 min. the solvents were evaporated and the residue was diluted with 5 mL water and extracted with ethyl acetate (2×5 mL). The organic extracts were combined, washed with brine, dried and concentrated. The residue was purified by flash chromatography to provide the title compound (40 mg, 62%); MS analysis electrospray, 320 (M+H).

Workup

  1. additionwas added
  2. customAfter 15 min. the solvents were evaporated
  3. additionthe residue was diluted with 5 mL water
  4. extractionextracted with ethyl acetate (2×5 mL)
  5. washwashed with brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-586d904ed9854fa5a61189bbb9756a06
Source dataset
uspto-grants-2012_11
Patent number
US08318723B2

Reaction notes

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