Hydrochloric Acid → HCID 22480171, compound

HRID 1353787Notes

Reaction equation

HRID 1353787 reaction equation
[C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:6]=CC=C[CH:2]=1.CCOC(/N=N/C(OCC)=O)=O.[OH:32][C:33]1[CH:34]=[C:35]([C:39]2[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([C:48]#[N:49])[CH:46]=3)[N:41](C3CCCCO3)[N:40]=2)[CH:36]=[CH:37][CH:38]=1.OC1C=C(C2C3[C:66](=CC=C(C#N)C=3)[N:65]([CH:74]3CCCCO3)N=2)C=CC=1.Cl>O1CCCC1>[CH3:66][N:65]([CH3:74])[CH2:2][CH2:1][CH2:6][O:32][C:33]1[CH:34]=[C:35]([C:39]2[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([C:48]#[N:49])[CH:46]=3)[NH:41][N:40]=2)[CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 69421900HCID 69421900, compound

Product 1

HCID 22480171HCID 22480171, compoundYield 56.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (1.31 g, 5.00 mmol), tetrahydrofuran (4.00 mL), 3-N,N-dimethylaminopropanol (0.592 mL, 5.00 mmol) and diethylazodicarboxylate (0.788 mL, 5.00 mmol) were added to 3-(3-hydroxyphenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile 3-(3-hydroxyphenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (0.400 g, 1.25 mmol). The mixture was stirred at ambient temperature for 15.5 h and poured into aqueous 6 N hydrochloric acid (30 mL). After stirring at ambient temperature for 4 h, the mixture was extracted with ethyl acetate (3×). The aqueous fraction was added to aqueous 6 N sodium hydroxide (30 mL) and the pH adjusted to 11. The solution was extracted with ethyl acetate (3×) and the organic fractions were combined and dried over anhydrous sodium sulfate, filtered and evaporated. Purification by flash chromatography on silica gel pretreated with 2% triethylamine/hexanes followed by 0–20% ethyl acetate/hexanes elution, sonication of the product in ethyl acetate (3 mL), addition of hexanes (20 mL) and filtration gave the title compound (0.225 g, 56% yield). ES-MS (m/z) 321 [M+1]+

Workup

  1. stirringAfter stirring at ambient temperature for 4 h
  2. extractionthe mixture was extracted with ethyl acetate (3×)
  3. additionThe aqueous fraction was added to aqueous 6 N sodium hydroxide (30 mL)
  4. extractionThe solution was extracted with ethyl acetate (3×)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by flash chromatography on silica gel
  9. washfollowed by 0–20% ethyl acetate/hexanes elution, sonication of the product in ethyl acetate (3 mL)
  10. additionaddition of hexanes (20 mL) and filtration

Sources & evidence

ORD record
ord-069377e8e6fb4570b6acadab292be356
Source dataset
uspto-grants-2007_05
Patent number
US07220771B2

Reaction notes

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