Triphenylphosphine → 2-Bromo-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine

HRID 423552Notes

Reaction equation

HRID 423552 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][OH:16])[CH2:11][CH2:10]2)[O:6][N:5]=1)[CH3:3].[Br:17][C:18]1[N:23]=[CH:22][C:21](O)=[CH:20][CH:19]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Br:17][C:18]1[CH:19]=[CH:20][C:21]([O:16][CH2:15][CH:12]2[CH2:13][CH2:14][N:9]([C:7]3[O:6][N:5]=[C:4]([CH:2]([CH3:1])[CH3:3])[N:8]=3)[CH2:10][CH2:11]2)=[CH:22][N:23]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 27628652-Bromo-5-hydroxypyridineHCID 57930076{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol

Product 1

HCID 866387382-Bromo-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridineYield 87.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Bromo-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyridine (1 g, 60%) was prepared from {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol (prepared as in Example 20, Step 3, 1 g, 4.4 mmol), 6-bromo-3-pyridinol (522 mg, 3 mmol), Ph3P (1.15 g, 4.4 mmol), diisopropyl azodicarboxylate (0.866 mL, 4.4 mmol), diisopropyl azodicarboxylate (0.866 mL, 4.4 mmol), and THF (15 mL) in a manner similar to Example 1, Step 2, and purified by reverse-phase preparative HPLC using a CH3CN:H2O gradient (30:70 to 100:0) with 0.05% TFA as a modifier. 1H NMR (400 MHz, CDCl3): δ 8.04 (d, 1H, J=3.1 Hz), 7.37 (d, 1H, J=8.7 Hz), 7.08 (dd, 1H, Ja=8.7 Hz, Jb=3.2 Hz), 4.22 (d, 2H, J=13.1 Hz), 3.85 (d, 2H, J=6.3 Hz), 3.09 (m, 2H), 2.89 (m, 1H), 2.13-1.99 (m, 1 H), 1.93 (d, 2H, J=12.4 Hz), 1.54-1.35 (m, 2H), 1.28 (d, 6H, J=6.9 Hz); LRMS (ESI m/z 381/383 (M+H).

Workup

  1. custompurified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-d029a3b19d7a42abada1afe025f40ed7
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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