5-methanesulfonyl-1-methyl-1H-1,2,3,4-tetrazole → 2-(2,6-Diethylphenyl)-4-methyl-6-(1-methyl-1H-tetrazol-5-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine

HRID 80828Notes

Reaction equation

HRID 80828 reaction equation
Cl.Cl.[CH2:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][CH3:12])[C:6]=1[C:13]1[CH:22]=[C:21]([CH3:23])[C:20]2[CH2:19][NH:18][CH2:17][CH2:16][C:15]=2[N:14]=1)[CH3:4].[CH3:24][N:25]1[C:29](S(C)(=O)=O)=[N:28][N:27]=[N:26]1>C1COCC1.[Li]CCCC.[Cl-].[Na+].O.CCOC(C)=O>[CH2:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][CH3:12])[C:6]=1[C:13]1[CH:22]=[C:21]([CH3:23])[C:20]2[CH2:19][N:18]([C:29]3[N:25]([CH3:24])[N:26]=[N:27][N:28]=3)[CH2:17][CH2:16][C:15]=2[N:14]=1)[CH3:4]

Participants

7

Reactant 2

HCID 64212595-methanesulfonyl-1-methyl-1H-1,2,3,4-tetrazoleHCID 86690277HCID 86690277, compound

Product 1

HCID 712404722-(2,6-Diethylphenyl)-4-methyl-6-(1-methyl-1H-tetrazol-5-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolventHCID 178418339ButyllithiumSolvent

Procedure

To a solution of 2-(2,6-diethylphenyl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine dihydrochloride (21.7 mg, 0.061 mmol) in THF (0.5 mL), 1.6 M n-BuLi in hexanes (0.119 mL, 0.190 mmol) was added at −78° C. under nitrogen. After stirring for 10 min. at the same temperature, 1-methyl-5-(methylsulfonyl)-1H-tetrazole (24.90 mg, 0.154 mmol) was added. The mixture was warmed up to rt and stirred for 19 h. The mixture was diluted with brine and EtOAc. The products were extracted with EtOAc, and the organic layer was concentrated. The crude was purified by RP-HPLC (X-Bridge Phenyl®, H2O (0.1% NH4OH)/CH3CN), then the fractions including the desired product were lyophilized to give the desired product. 1H NMR (400 MHz, CDCl3) δ ppm 7.26-7.30 (m, 2 H), 7.14 (d, J=7.58 Hz, 1 H), 6.98 (s, 1 H), 4.58 (s, 2 H), 4.01 (s, 3 H), 3.68 (t, J=5.94 Hz, 2 H), 3.25 (br t, J=5.94 Hz, 2 H), 2.30-2.37 (m, 7 H), 1.06 (t, J=7.58 Hz, 6 H); MS (ESI+) m/z 363.27 (M+H)+.

Workup

  1. additionwas added
  2. extractionThe products were extracted with EtOAc
  3. concentrationthe organic layer was concentrated
  4. customThe crude was purified by RP-HPLC (X-Bridge Phenyl®, H2O (0.1% NH4OH)/CH3CN)

Sources & evidence

ORD record
ord-d8a04dedffa740b591448921b5b0c1d4
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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