Water ethanol → HCID 86673711, compound

HRID 1025593Notes

Reaction equation

HRID 1025593 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH:34]=[O:35])=[C:19]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]([C:32]#[N:33])=[CH:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].O.C([OH:39])C>O.O1CCCC1>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH:34]=[O:35])=[C:19]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]([C:32]([NH2:33])=[O:39])=[CH:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 19096565Water ethanolHCID 86673709HCID 86673709, compound

Product 1

HCID 86673711HCID 86673711, compound

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

A round bottom flask containing 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-1H-indole-3 carbonitrile (12 mg, 0.03 mmol) was taken up in 10% water/tetrahydrofuran (1.5 ml). Next hydrido(dimethylphosphinousacid-kp)[hydrogen bis-(dimethylphosphinito-kp)]platinum(II) catalyst (2 mg, 0.005 mmol) was added and the mixture was heated to reflux (oil bath). After 1 hour the mixture was cooled to ambient and the volatiles stripped (rotary evaporator) to provide a crude product. This reaction (as described above—but using 10% H2O/ethanol as solvent) was repeated on a 61 mg scale (0.24 mmol) and worked up as described. The combined crude material from the 2 reactions was purified by preparative thin layer chromatography (3 plates, eluting with 5% MeOH/CH2Cl2 and then re-developing again with 5% MeOH/CH2Cl2). The product band was collected to provide 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-1H-indole-3-carboxamide as a light yellow solid (51 mg). LC/MS calcd for C28H23FN4O3 (m/e) 482.52, obsd 483.0 (M+H, ES+): 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 9H) 6.03 (br. s, 2H) 7.20-7.36 (m, 3H) 7.44-7.59 (m, 3H) 7.66 (d, J=7.93 Hz, 1H) 7.81 (t, J=7.60 Hz, 1H) 7.91 (s, 1H) 8.19 (m, 1H) 8.23 (d, J=2.64 Hz, 1H) 9.52 (s, 1H)

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux (oil bath)
  3. temperatureAfter 1 hour the mixture was cooled to ambient and the volatiles
  4. custom(rotary evaporator)
  5. customto provide a crude product
  6. customwas purified by preparative thin layer chromatography (3 plates
  7. washeluting with 5% MeOH/CH2Cl2
  8. customThe product band was collected

Sources & evidence

ORD record
ord-62493d22132e45ae8760baeb2b2fbdbe
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

Loading…