Acetone → HCID 67956826, compound

HRID 872288Notes

Reaction equation

HRID 872288 reaction equation
Br[C:2]1[C:3]([O:8][C:9]2[CH:21]=[CH:20][C:12]3[N:13]([CH2:16][CH:17]4[CH2:19][CH2:18]4)[N:14]=[N:15][C:11]=3[C:10]=2[Cl:22])=[N:4][CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH3:28][C:29]([CH3:31])=[O:30].O>O1CCCC1>[Cl:22][C:10]1[C:11]2[N:15]=[N:14][N:13]([CH2:16][CH:17]3[CH2:19][CH2:18]3)[C:12]=2[CH:20]=[CH:21][C:9]=1[O:8][C:3]1[C:2]([C:29]([OH:30])([CH3:31])[CH3:28])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 180AcetoneHCID 962Water2×HCID 67955438HCID 67955438, compoundHCID 178418339Butyllithium

Product 1

HCID 67956826HCID 67956826, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

5-[(3-Bromopyridin-2-yl)oxy]-4-chloro-1-(cyclopropylmethyl)-1H-benzotriazole (395, 33 mg, 0.09 mmol, 1 equiv) was dissolved in anhydrous tetrahydrofuran (2 mL), cooled to −70° C. and treated dropwise with n-butyllithium (2.5 M in tetrahydrofuran, 0.038 mL, 0.10 mmol, 1.1 equiv.). After 5 minutes, the mixture was treated with acetone (7.57 mg, 0.13 mmol, 1.5 equiv.). After an additional ten minutes at −70° C., the mixture was treated with water. The mixture was poured into water (40 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC (80:20 to 5:95; water containing 0.05% trifluoroacetic acid:acetonitrile containing 0.05% trifluoroacetic acid). The appropriate fractions were poured into sodium bicarbonate (saturated aqueous, 20 mL) and extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo to afford the titled compound 396 as a white solid. 1H NMR (400 MHz, d6-DMSO) δ 8.10 (dd, 1H, J=7.6, 1.9 Hz), 7.97 (d, 1H, J=8.9 Hz), 7.88 (dd, 1H, J=4.8, 1.8 Hz), 7.44 (d, 1H, J=9.2 Hz), 7.14 (dd, 1H, J=7.4, 4.6 Hz), 4.66 (d, 2H, J=7.5 Hz), 1.68 (s, 6H), 1.45-1.38 (m, 1H), 0.60-0.57 (m, 2H), 0.52-0.49 (m, 2H) ppm. High resolution mass spectrometry (ES+) m/z 359.1277 [(M+H)+; calculated for C18H20ClN4O2: 359.1269].

Workup

  1. waitAfter an additional ten minutes at −70° C.
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via preparative reverse phase HPLC (80:20 to 5:95; water containing 0.05% trifluoroacetic acid:acetonitrile containing 0.05% trifluoroacetic acid)
  7. additionThe appropriate fractions were poured into sodium bicarbonate (saturated aqueous, 20 mL)
  8. extractionextracted with ethyl acetate (2×20 mL)
  9. dry with materialThe combined organic extracts were dried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dfd553804aef41fc9e5701b270f0c42c
Source dataset
uspto-grants-2015_03
Patent number
US08975286B2

Reaction notes

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