3-Pyridinemethanol → HCID 69894256, compound

HRID 1794291Notes

Reaction equation

HRID 1794291 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[CH2:46][C:47]1[CH:48]=[N:49][CH:50]=[CH:51][CH:52]=1.N(C(OCC)=O)=NC(OCC)=O>ClCCl>[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]([O:44][CH2:46][C:47]1[CH:48]=[N:49][CH:50]=[CH:51][CH:52]=1)=[CH:40][CH:39]=3

Participants

6

Reactant 4

HCID 75103-PyridinemethanolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22220927HCID 22220927, compound

Product 1

HCID 69894256HCID 69894256, compoundYield 16.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under nitrogen atmosphere, triphenylphosphine bound resin (0.41 g, 0.45 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 (0.1 g, 0.30 mmol) (prepared by Example 3 step (a)), 3-hydroxymethylpyridine (44 μl, 0.45 mmol, 1.5 eq.) and diethyl azodicarboxylate (71 μl, 0.45 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 diethyl ether. The combined organics were concentrated in vacuo. The residue was purified firstly by alumina chromatography, eluting with 1% methanol/dichloromethane, and secondly by silica chromatography, using dichloromethane→5% methanol/dichloromethane as the eluant, to afford the title compound (21 mg, 16%). 1H NMR (400 MHz, CDCl3) δ 8.70–8.69 (1H, m), 8.61–8.59 (1H, m), 7.80 (1H, dt, J=7.8, 2.1 Hz), 7.59 (1H, d, J=2.4 Hz), 7.54–7.52 (2H, m), 7.46–7.33 (4H, m), 7.18 (1H, d, J=8.4 Hz), 7.02 (1H, dd, J=8.4, 2.4 Hz), 5.16 (2H, s), 3.96 (2H, s), 2.70 (3H, s). m/z (ES+) 422 (M+H)+.

Workup

  1. filtrationThe resin was filtered off
  2. washwashed with dichloromethane, methanol and diethyl ether
  3. concentrationThe combined organics were concentrated in vacuo
  4. customThe residue was purified firstly by alumina chromatography
  5. washeluting with 1% methanol/dichloromethane

Sources & evidence

ORD record
ord-e7d2722e616d4e47af2d3e076ccaaa0e
Source dataset
uspto-grants-2006_04
Patent number
US07022724B2

Reaction notes

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