Hydrochloric Acid → 1-(5-(1H-1,2,4-Triazol-3-Yl)(1H-Indazol-3-Yl))-3-(2-Piperazinylethoxv)benzene

HRID 1272875Notes

Reaction equation

HRID 1272875 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC([CH:27]1[CH2:32][NH:31][CH2:30][CH2:29][N:28]1[CH:33](O)[CH3:34])=O)(C)(C)C.CCOC(/N=N/C(OCC)=O)=O.O1CCCCC1[N:54]1[C:62]2[C:57](=[CH:58][C:59]([C:63]3[N:67]=[CH:66][N:65](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:64]=3)=[CH:60][CH:61]=2)[C:56]([C:87]2[CH:88]=[C:89]([OH:93])[CH:90]=[CH:91][CH:92]=2)=[N:55]1.Cl>O1CCCC1>[NH:64]1[C:63]([C:59]2[CH:58]=[C:57]3[C:62](=[CH:61][CH:60]=2)[NH:54][N:55]=[C:56]3[C:87]2[CH:92]=[CH:91][CH:90]=[C:89]([O:93][CH2:34][CH2:33][N:28]3[CH2:27][CH2:32][NH:31][CH2:30][CH2:29]3)[CH:88]=2)=[N:67][CH:66]=[N:65]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 224797613-(1-(Tetrahydro-2H-pyran-2-yl)-5-(1-trityl-1H-1,2,4-triazol-3-yl)-1H-indazol-3-yl)phenolHCID 224800832-(Tert-butyloxycarbonyl)piperazinylethanol

Product 1

HCID 207890361-(5-(1H-1,2,4-Triazol-3-Yl)(1H-Indazol-3-Yl))-3-(2-Piperazinylethoxv)benzeneYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), 2-(tert-butyloxycarbonyl)piperazinylethanol (0.610 g, 2.65 mmol) and diethylazodicarboxylate (0.418 mL, 2.65 mmol) were added to 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenol (0.400 g, 0.662 mmol). The mixture was stirred at ambient temperature for 23 h and poured into aqueous 6N hydrochloric acid (25 mL). After stirring at ambient temperature for 4 h, the mixture was extracted with ether (3×). The aqueous fraction was added to aqueous 6 N sodium hydroxide (25 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. The residue was purified by preparative HPLC (5–70% acetonitrile/water). The desired fractions were concentrated, dissolved in ethyl acetate, washed with aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated to give the title compound (0.132 g, 52% yield) as the bis-trifluoroacetic acid salt. 1H NMR (D2O) δ 8.26 (s, 1H), 8.12 (s, 1H), 7.61 (d, 1H), 7.37 (d, 1H), 7.31 (m, 2H), 7.19 (m, 1H), 6.90 (m, 1H), 4.35 (m, 2H), 3.62 (m, 6H), 3.52 (m, 4H). ES-MS (m/z) 390 [M+1]+.

Workup

  1. stirringAfter stirring at ambient temperature for 4 h
  2. extractionthe mixture was extracted with ether (3×)
  3. additionThe aqueous fraction was added to aqueous 6 N sodium hydroxide (25 mL)
  4. extractionThe solution was extracted with ethyl acetate (3×)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by preparative HPLC (5–70% acetonitrile/water)
  9. concentrationThe desired fractions were concentrated
  10. dissolutiondissolved in ethyl acetate
  11. washwashed with aqueous sodium bicarbonate
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. customevaporated

Sources & evidence

ORD record
ord-c4fa81257522416fb8689ecc631f1010
Source dataset
uspto-grants-2007_04
Patent number
US07208513B2

Reaction notes

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