Sodium hydride → HCID 86722448, compound

HRID 718840Notes

Reaction equation

HRID 718840 reaction equation
[C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].[H-].[Na+].[Br:14][C:15]1[C:16]2[O:34][CH2:33][CH2:32][C:31](=O)[C:17]=2[CH:18]=[C:19]2[C:23]=1[N:22]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[N:21]=[CH:20]2>COCCOC>[Br:14][C:15]1[C:16]2[O:34][CH2:33][CH2:32][C:31](=[CH:3][C:1]#[N:2])[C:17]=2[CH:18]=[C:19]2[C:23]=1[N:22]([C:24]1[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=1)[N:21]=[CH:20]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 86722446HCID 86722446, compound

Product 1

HCID 86722448HCID 86722448, compoundYield 18.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Diethyl (cyanomethyl)phosphonate (11.2 mL, 69.2 mmol) was added dropwise to a slurry of sodium hydride (60 wt % in oil, 2.76 g, 68.9 mmol) in DME (120 mL) under a nitrogen atmosphere at about 0° C. over about 15 min. After completion of addition, the ice bath was removed. After about 30 min, the solution was added to a slurry of 9-bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5 (1H)-one (99, R1=4-Fluorophenyl) (12.5 g, 34.5 mmol) and DME (60 mL) rinsing with DME (60 mL). After about 43 h, the volatiles were removed under under reduced pressure and the residue was dissolved with EtOAc (300 mL) and sat. aq. NH4Cl solution (300 mL). The layers were separated. The organic layer was washed with sat. aq. NaCl (200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was slurried in DCM (20 mL). The solid was collected by filtration rinsing with DCM (10 mL) then dried under reduced pressure to afford 2-(9-Bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5(1H)-ylidene)acetonitrile (100, R1=4-Fluorophenyl) (2.41 g, 18% yield) as an ivory solid. The mother liquor was purified on silica gel (220 g) using a gradient of 0-2% EtOAc in DCM. The fractions containing the product were combined and concentrated under reduced pressure to afford 2-(9-Bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5(1H)-ylidene)acetonitrile (100, R1=4-Fluorophenyl) (4.92 g, 37% yield) as an ivory solid. LC/MS, method 3, Rt=2.42 min, MS m/z 384 and 386 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.69 (s, 0.33H), 8.50 (s, 0.33H), 8.46 (s, 0.67H), 8.39 (s, 0.67H), 7.60-7.51 (m, 2H), 7.42-7.30 (m, 2H), 6.50-6.46 (m, 0.67H), 5.84-5.81 (m, 0.33H), 4.48-4.42 (m, 0.67H), 4.42-4.36 (m, 1.33H), 3.06-2.98 (m, 1.33H), 2.88-2.82 (m, 0.67H).

Workup

  1. additionAfter completion of addition
  2. customthe ice bath was removed
  3. washrinsing with DME (60 mL)
  4. waitAfter about 43 h
  5. customthe volatiles were removed under under reduced pressure
  6. dissolutionthe residue was dissolved with EtOAc (300 mL) and sat. aq. NH4Cl solution (300 mL)
  7. customThe layers were separated
  8. washThe organic layer was washed with sat. aq. NaCl (200 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. filtrationThe solid was collected by filtration
  13. washrinsing with DCM (10 mL)
  14. customthen dried under reduced pressure

Sources & evidence

ORD record
ord-ee1f76a861d540cea63c03ca0565aab2
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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