Trifluoroacetic acid → 4-Bromo-1-(2,2-dimethylpropyl)-5-(pyrazin-2-ylmethoxy)-1H-1,2,3-benzotriazole

HRID 1626966Notes

Reaction equation

HRID 1626966 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[OH:16].[N:17]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[CH2:23]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C(O)(C(F)(F)F)=O>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:13])([CH3:15])[CH3:14])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:16][CH2:23][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][N:17]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 201734PyrazinemethanolHCID 57424995HCID 57424995, compound

Product 1

HCID 676071664-Bromo-1-(2,2-dimethylpropyl)-5-(pyrazin-2-ylmethoxy)-1H-1,2,3-benzotriazole

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-ol (Example 1-2) (1.5 g, 5.28 mmol, 1.0 equiv.), 2-pyrazinylmethanol (13) (0.581 g, 5.28 mmol, 1.0 equiv.) and polymer-supported triphenylphosphine (2.2 mmol/g, 5.75 g, 21.91 mmol, 2.5 equiv.) in THF (37.7 ml) and DCM (37.7 ml) was slowly added di-tert-butyl azodicarboxylate (2.431 g, 10.56 mmol, 2.0 equiv.). After stirring at room temperature for 1 hr, the reaction mixture was passed through a filter. The residue was washed with DCM and THF. The filtrate was concentrated to dryness to give a solid, which was taken up in DCM (12 mL) and treated with TFA (6 mL). The mixture was stirred at room temperature until LCMS showed only the desired product. The reaction mixture was neutralized to pH=7 with saturated aqueous NaHCO3, and then extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (EtOAc/Hexane gradient from 0 to 100%) to obtain product Example 4-1. 1H NMR δ (CDCl3): 9.06 (s, 1H), 8.59-8.57 (m, 2H), 7.42 (d, 1H, J=9.5 Hz), 7.31 (d, 1H, J=9.0 Hz), 5.38 (s, 2H), 4.38 (s, 2H), 1.04 (s, 9H) ppm. LRMS m/z (M+H) 376.1 and 378.1 (intensity ratio ˜1:1) found, 376.1 and 378.1 required.

Workup

  1. washThe residue was washed with DCM and THF
  2. concentrationThe filtrate was concentrated to dryness
  3. customto give a solid, which
  4. stirringThe mixture was stirred at room temperature until LCMS

Sources & evidence

ORD record
ord-44d75c2e7f7a47a6a736a758a6b7460d
Source dataset
uspto-grants-2014_07
Patent number
US08785481B2

Reaction notes

Loading…