Triphenylphosphine → HCID 66558997, compound

HRID 1530582Notes

Reaction equation

HRID 1530582 reaction equation
C(OC(N1CC[CH:14]([CH:17]([O:20][C:21]2[CH:43]=[CH:42][C:24]3[C:25]4[N:29]([CH2:30][CH2:31][O:32][C:23]=3[CH:22]=2)[CH:28]=[C:27]([C:33]2[N:34]([CH:39]([CH3:41])[CH3:40])[N:35]=[C:36]([CH3:38])[N:37]=2)[N:26]=4)CC)CC1)=O)C1C=CC=CC=1.OC([C:47]1[CH:48]=[C:49]([CH:52]=[CH:53][CH:54]=1)[C:50]#[N:51])C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCOCC1>[CH:39]([N:34]1[C:33]([C:27]2[N:26]=[C:25]3[C:24]4[CH:42]=[CH:43][C:21]([O:20][CH:17]([C:47]5[CH:48]=[C:49]([CH:52]=[CH:53][CH:54]=5)[C:50]#[N:51])[CH3:14])=[CH:22][C:23]=4[O:32][CH2:31][CH2:30][N:29]3[CH:28]=2)=[N:37][C:36]([CH3:38])=[N:35]1)([CH3:41])[CH3:40]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 112288753-(1-hydroxyethyl)benzonitrileHCID 68312705HCID 68312705, compound

Product 1

HCID 66558997HCID 66558997, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol from Example 4 (300 mg, 0.92 mmol), 3-(1-hydroxyethyl)benzonitrile (390 mg, 2.65 mmol) and triphenylphosphine (600 mg, 2.28 mmol) in dioxane (10 mL) was added dropwise DIAD (449 ul, 2.28 mmol) and the reaction mixture was stirred at RT for 18 h under an argon atmosphere. Volatiles were removed in vacuo and the resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in EtOAc). The product containing fractions were combined and concentrated under reduced pressure. The resulting residue was stirred in aq. NaOH (2M) for 15 min and then was filtered off. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 25 min gradient 50-100% 0.1% HCO2H in acetonitrile/water) affording 191 (29 mg, 7%). LCMS: RT 4.81 min [M+H]+ 455.2. 1H NMR (DMSO, 400 MHz): δ 8.26 (1H, d, J=8.97 Hz), 7.93-7.89 (1H, m), 7.82-7.74 (3H, m), 7.60 (1H, t, J=7.78 Hz), 6.80 (1H, dd, J=9.00, 2.57 Hz), 6.57 (1H, d, J=2.54 Hz), 5.87-5.75 (1H, m), 5.66 (1H, q, J=6.38 Hz), 4.49-4.40 (4H, m), 2.25 (3H, s), 1.59 (3H, d, J=6.35 Hz), 1.45 (6H, d, J=6.60 Hz)

Workup

  1. customVolatiles were removed in vacuo
  2. customthe resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in EtOAc)
  3. additionThe product containing fractions
  4. concentrationconcentrated under reduced pressure
  5. stirringThe resulting residue was stirred in aq. NaOH (2M) for 15 min
  6. filtrationwas filtered off
  7. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 25 min gradient 50-100% 0.1% HCO2H in acetonitrile/water)

Sources & evidence

ORD record
ord-e39b3c9caa2146a7ad8ef1307266a6b6
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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