Di-3-pyridinylmethanone → (+/-)-2-(4-fluorophenyl)-2-(2-methyl-2H-tetrazol-5-yl)-1,1-dipyridin-3-ylethanol

HRID 2099588Notes

Reaction equation

HRID 2099588 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][C:7]2[N:8]=[N:9][N:10]([CH3:12])[N:11]=2)=[CH:4][CH:3]=1.FC1C=CC(CC2N(C)N=NN=2)=CC=1.[Li]CCCC.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)=[O:41])[CH:35]=1>CCOCC.O1CCCC1>[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH:6]([C:7]2[N:8]=[N:9][N:10]([CH3:12])[N:11]=2)[C:40]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)([C:36]2[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=2)[OH:41])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 298471Di-3-pyridinylmethanoneHCID 687998105-(4-fluorobenzyl)-2-methyl-2H-tetrazoleHCID 688035225-(4-fluorobenzyl)-1-methyl-1H-tetrazoleHCID 178418339Butyllithium

Product 1

HCID 11588893(+/-)-2-(4-fluorophenyl)-2-(2-methyl-2H-tetrazol-5-yl)-1,1-dipyridin-3-ylethanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a 1:1 mixture of 5-(4-fluorobenzyl)-2-methyl-2H-tetrazole and 5-(4-fluorobenzyl)-1-methyl-1H-tetrazole, (0.209 g, 1.09 mmol) in 10 mL of 1:1 ether:tetrahydrofuran at −78° C. was added dropwise n-BuLi (0.434 mL of 2.5 M in hexane, 1.09 mmol). After stirring for one hour, a solution of dipyridin-3-ylmethanone (200 mg, 1.09 mmol) in 3 mL of tetrahydrofuran was added dropwise. Afterh 30 minutes, the reaction was quenched by transferring it via cannula to a −78° C. solution of 100 mL of ether containing 1 mL of concentrated aqueous HCl solution. After concentrating the mixture in vacuo, the resulting residue was taken up in EtOAc and extracted with 10% aqueous Na2CO3 solution and brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by preparative reverse-phase HPLC to provide the titled compound, along with a regioisomer (Example VII-4). 1H NMR (500 MHz, d6-DMSO): δ 8.91 (br s, 1H), 8.66 (br s, 1H), 8.36 (d, J=4.4 Hz, 1H), 8.24 (d, J=4.4 Hz, 1H), 8.07 (br d, J=8.3 Hz, 1H), 7.82 (br d, J=8.0 Hz, 1H), 7.51 (dd, J =8.7 and 5.6 Hz, 2H), 7.29 (dd, J=8.3 and 4.9 Hz, 1H), 7.16 (dd, J=8.0 and 4.6 Hz, 1H), 6.95 (t, J=9.0 Hz, 2H), 6.16 (s, 1H), 6.05 (s, 1H), 4.23 (s, 3H). HRMS [M+H] C20H18FN6O calcd 377.1521 , found 377.1527.

Workup

  1. waitAfterh 30 minutes
  2. customthe reaction was quenched
  3. customto a −78° C.
  4. concentrationAfter concentrating the mixture in vacuo
  5. extractionextracted with 10% aqueous Na2CO3 solution and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-656aaef3033548648ae46ca060b7f245
Source dataset
uspto-grants-2009_08
Patent number
US07569589B2

Reaction notes

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