Triphenylphosphine → Gsk-1292263

HRID 423664Notes

Reaction equation

HRID 423664 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:15][S:16]([C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=2)=[CH:21][CH:20]=1)(=[O:18])=[O:17].[CH3:32][CH:33]([C:35]1[N:39]=[C:38]([N:40]2[CH2:45][CH2:44][CH:43]([CH2:46]O)[CH2:42][CH2:41]2)[O:37][N:36]=1)[CH3:34].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1>[CH3:34][CH:33]([C:35]1[N:39]=[C:38]([N:40]2[CH2:41][CH2:42][CH:43]([CH2:46][O:31][C:28]3[CH:27]=[CH:26][C:25]([C:22]4[CH:21]=[CH:20][C:19]([S:16]([CH3:15])(=[O:18])=[O:17])=[CH:24][CH:23]=4)=[N:30][CH:29]=3)[CH2:44][CH2:45]2)[O:37][N:36]=1)[CH3:32]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 532295926-(4-(Methylsulfonyl)phenyl)pyridin-3-olHCID 57930076{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol

Product 1

HCID 24996872Gsk-1292263Yield 81.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropyl azodicarboxylate (0.175 mL, 0.89 mmol) was added dropwise to a solution of 6-[4-(methylsulfonyl)phenyl]-3-pyridinol (150 mg, 0.59 mmol), {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol (prepared as in Example 20, Steps 1-3, 200 mg, 0.89 mmol), PPh3 (233 mg, 0.89 mmol), and THF (10 mL) at ambient temperature. The mixture was stirred at ambient temperature for 4 h. The mixture was concentrated, and the resulting crude was purified by reverse-phase preparative HPLC using a CH3CN:H2O gradient (10:90 to 100:0) with 0.05% TFA as a modifier, then taken up in CH2Cl2 and free-based with saturated NaHCO3 (aq) to give 5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfonyl)phenyl]pyridine (220 mg) as a white solid.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe resulting crude was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-26636bf705aa41538b918b312688d1ee
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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