Toluene → HCID 178441620, compound

HRID 1450488Notes

Reaction equation

HRID 1450488 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:13]([CH2:14][CH2:15][CH2:16][CH3:17])=[N:12][C:11]([CH2:18][CH2:19][CH2:20][CH3:21])=[N:10]2)=[N:6][CH:7]=1.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:29]2[C:33]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3B(O)O)=[N:32][N:31]=[N:30]2)C=CC=CC=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[CH2:18]([C:11]1[N:12]=[C:13]([CH2:14][CH2:15][CH2:16][CH3:17])[N:9]([CH2:8][C:5]2[N:6]=[CH:7][C:2]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[C:33]3[NH:32][N:31]=[N:30][N:29]=3)=[CH:3][CH:4]=2)[N:10]=1)[CH2:19][CH2:20][CH3:21]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 103427452-(1-Trityl-1H-tetrazol-5-YL)phenylboronic acidHCID 199766265-bromo-2-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]pyridine

Product 1

HCID 178441620HCID 178441620, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

Under nitrogen, 2.04 g (5.8 mmol) of 5-bromo-2-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]pyridine from step 4 and 2.83 g (6.6 mmol) of 2-(N-triphenylmethyltetrazol-5-yl)phenylboronic acid from step 5 were treated with 1.0 g (0.86 mmol) of tetrakis(triphenylphosphine)palladium zero, 18 mL of toluene, 14 mL of ethanol, and 7.5 mL of 2M aqueous sodium carbonate. The reaction mixture was heated to reflux and vigorously stirred overnight. The product was purified by reverse phase chromatography (Waters Deltaprep-3000) using acetonitrile/water (20-40:80-60) (0.05% TFA). The pure fractions (by analytical HPLC) were combined, the acetonitrile removed in vacuo, the pH adjusted to four with dilute sodium hydroxide, and the resulting suspension extracted 4 times with ether. The extracts were combined, dried (MgSO4), and concentrated in vacuo to give 710 mg (30%) of 5-[2-[6-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-3-pyridinyl]phenyl]-1H-tetrazole as a colorless solid: mp 136°-138° C.; NMR (CD3OD) δ0.88-0.98 (m, 6H), 1.27-1.45 (m, 4H), 1.60-1.75 (m, 4H), 2.66 (t, J=7 Hz, 2H), 2.84 (t, J=7 Hz, 2H), 5.45 (s, 2H), 7.21 (d, J=8 Hz, 1H), 7.56-7.68 (m, 3H), 7.70-7.78 (m, 2H), 8.29 (d, J=2 Hz, 1H); MS (FAB) m/e (rel intensity) 417 (100), 389 (10), 374 (10), 360 (10), 208 (35), 182 (25); HRMS. Calc'd for M+H: 417.2515. Found: 417.2486.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux and vigorously stirred overnight
  3. customThe product was purified by reverse phase chromatography (Waters Deltaprep-3000)
  4. customthe acetonitrile removed in vacuo
  5. extractionthe resulting suspension extracted 4 times with ether
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-15b0ce2a362b469d879c3c404335fe74
Source dataset
uspto-grants-1997_02
Patent number
US05602153

Reaction notes

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