Water → HCID 56655590, compound

HRID 1431074Notes

Reaction equation

HRID 1431074 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[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH2:37][C@@H:38]([O:42][Si](C(C)(C)C)(C)C)[CH2:39][O:40][CH3:41])=[CH:32][N:31]=4)[C:26](=[O:50])[N:25]([CH3:51])[N:24]=3)[C:18]=1[CH2:52][OH:53])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].O.[Na+].[Cl-]>C1COCC1.CCOC(C)=O.CCCCCC>[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[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH2:37][C@@H:38]([OH:42])[CH2:39][O:40][CH3:41])=[CH:32][N:31]=4)[C:26](=[O:50])[N:25]([CH3:51])[N:24]=3)[C:18]=1[CH2:52][OH:53])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 5234Sodium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 66743161HCID 66743161, compound

Product 1

HCID 56655590HCID 56655590, compoundYield 61.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

In a 100 mL round-bottomed flask, (S)-6-tert-butyl-2-(3-(5-(5-(2-(tert-butyldimethylsilyloxy)-3-methoxypropoxy)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one (214 mg, 287 μmol, Eq: 1.00) was combined with THF (6.0 ml) to give a yellow solution. TBAF (500 μl of a 1M solution in THF, 500 μmol) was added and the resultant solution was stirred at 25° C. for 1 h. The reaction was complete by LCMS. The reaction mixture was poured into 75 mL H2O and extracted with EtOAc (1×75 mL). An emulsion resulted. Saturated NaCl was added and the EtOAc layer was separated. Extracted 2 times with DCM. No product left in aqueous phase by LCMS. The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0.5% to 4% MeOH in DCM) to afford a glass. The glass was taken up in EtOAc/hexane and conc. to give a semisolid, which was triturated with ether. The resulting white solid was washed with ether/hexanes to give 112 mg of pure product as a white powder. (M+H)+=631 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9H) 3.44 (s, 3H) 3.53-3.64 (m, 2H) 3.91 (s, 3H) 4.03-4.11 (m, 2H) 4.13-4.22 (m, 1H) 4.42 (s, 2H) 6.98 (d, J=8.69 Hz, 1H) 7.28-7.35 (m, 1H) 7.43-7.62 (m, 4H) 7.64-7.69 (m, 1H) 8.06 (d, J=3.02 Hz, 1H) 8.27-8.32 (m, 2H) 8.48 (s, 1H)

Workup

  1. customto give a yellow solution
  2. extractionextracted with EtOAc (1×75 mL)
  3. customAn emulsion resulted
  4. customthe EtOAc layer was separated
  5. extractionExtracted 2 times with DCM
  6. waitNo product left in aqueous phase by LCMS
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0.5% to 4% MeOH in DCM)
  10. customto afford a glass
  11. customconc. to give a semisolid, which
  12. customwas triturated with ether
  13. washThe resulting white solid was washed with ether/hexanes

Sources & evidence

ORD record
ord-d758ce187a8641a1af07cb96200d437d
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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