Triphenylphosphine → HCID 69897632, compound

HRID 1794292Notes

Reaction equation

HRID 1794292 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][C:21]1[O:25][N:24]=[C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:22]=1[C:32]1[N:36]2[CH2:37][C:38]3[C:43]([C:35]2=[N:34][N:33]=1)=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=3.O[CH:46]1[CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][CH2:47]1.N(C(OCC)=O)=NC(OCC)=O>ClCCl.C(O)(C(F)(F)F)=O>[C:55]([O:54][C:52]([N:49]1[CH2:50][CH2:51][CH:46]([O:44][C:41]2[CH:42]=[C:43]3[C:38]([CH2:37][N:36]4[C:32]([C:22]5[C:23]([C:26]6[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=6)=[N:24][O:25][C:21]=5[CH3:20])=[N:33][N:34]=[C:35]43)=[CH:39][CH:40]=2)[CH2:47][CH2:48]1)=[O:53])([CH3:58])([CH3:56])[CH3:57]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 22220927HCID 22220927, compound

Product 1

HCID 69897632HCID 69897632, compoundYield 1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Under nitrogen atmosphere, triphenylphosphine bound resin (1.22 g, 1.36 mmol, 1.12 mmol/g) was swelled in dichloromethane for 30 minutes. 3-(5-Methyl-3-phenylisoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-a]isoindol-8-ol (0.3 g, 0.91 mmol) (prepared as in Example 3, Step (a)), 4-hydroxy-boc-piperidine (0.27 g, 1.36 mmol, 1.5 eq.) and diethyl azodicarboxylate (0.21 ml, 1.36 mmol, 1.5 eq.) were added and the reaction was stirred at room temperature overnight. The resin was filtered off and washed with dichloromethane, methanol and ether. The combined organics were concentrated in vacuo. The residue was purified by alumina chromatography, eluting with dichloromethane 2% methanol/dichloromethane (0.5% methanol gradient), and was used without further purification in the next step. b) 3-(5-Methyl-3-phenylisoxazol-4-yl)-8-(piperidin-4-yloxy)-5H-[1,2,4]triazolo[3,4-α]isoindole 4-[3-(5-Methyl-3-phenylisoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-α]isoindol-8-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (466 mg, 0.91 mmol) was dissolved in TFA (5 ml) and stirred at room temperature for 1 hour. The reaction was concentrated in vacuo and the residue was partitioned between ethyl acetate and saturated K2CO3 (aq). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by alumina chromatography, eluting with dichloromethane→5% methanol/dichloromethane (in 1% methanol gradient), to afford the title compound as a white solid (4 mg, 1% over 2 steps). 1H NMR (400 MHz, d4 MeOH) δ 7.53–7.43 (6H, m), 7.32 (1H, d, J=8.5 Hz), 7.08 (1H, dd, J=8.5, 2.4 Hz), 4.63–4.60 (1H, m), 4.24 (2H, s), 3.16–3.11 (2H, m), 2.85–2.79 (2H, m), 2.64 (3H, s), 2.09–2.05 (2H, m), 1.78–1.72 (2H, m). m/z (ES+) 414 (M+H)+.

Workup

  1. filtrationThe resin was filtered off
  2. washwashed with dichloromethane, methanol and ether
  3. concentrationThe combined organics were concentrated in vacuo
  4. customThe residue was purified by alumina chromatography
  5. washeluting with dichloromethane 2% methanol/dichloromethane (0.5% methanol gradient)
  6. customwas used without further purification in the next step
  7. stirringstirred at room temperature for 1 hour
  8. concentrationThe reaction was concentrated in vacuo
  9. customthe residue was partitioned between ethyl acetate and saturated K2CO3 (aq)
  10. dry with materialThe organic layer was dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by alumina chromatography
  14. washeluting with dichloromethane→5% methanol/dichloromethane (in 1% methanol gradient)

Sources & evidence

ORD record
ord-49bc46c8fe3249c395c42e9b07daea19
Source dataset
uspto-grants-2006_04
Patent number
US07022724B2

Reaction notes

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