2,6-Lutidine → HCID 66628259, compound

HRID 1046894Notes

Reaction equation

HRID 1046894 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]3[N:15]=[C:16]([O:18][CH3:19])[N:17]=[C:13]3[NH:12][C:11]([CH3:20])=[C:10]2[C:21]#[N:22])=[CH:5][CH:4]=1)#[N:2].[F:23][C:24]([F:35])([F:34])[C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1.C(N(CC)CC)C.N1C(C)=CC=CC=1C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.N1C=CC=CC=1.ClCCl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]3[N:15]=[C:16]([O:18][CH3:19])[N:17]=[C:13]3[N:12]([C:29]3[CH:28]=[CH:27][CH:26]=[C:25]([C:24]([F:35])([F:34])[F:23])[CH:30]=3)[C:11]([CH3:20])=[C:10]2[C:21]#[N:22])=[CH:5][CH:4]=1)#[N:2]

Participants

8

Reactant 4

HCID 79372,6-LutidineHCID 8471TriethylamineHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 136355656HCID 136355656, compound

Product 1

HCID 66628259HCID 66628259, compound

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalyst2×HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Under an atmosphere of argon protective gas, (rac)-7-(4-cyanophenyl)-2-methoxy-5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (50 mg, 171 μmol) was stirred in abs. dichloromethane (7 ml) with molecular sieve (0.5 g, 4 Å) for 1 h. 3-(Trifluoromethyl)phenylboronic acid (97 mg, 513 μmol, 3 eq.), anhydrous copper(II) acetate (93 mg, 513 μmol, 3 eq.), abs. pyridine (8 ml) and triethylamine (72 μl, 513 μmol, 3 eq.) were then added, and the mixture was stirred at RT for 48 h. More anhydrous copper(II) acetate (31 mg, 171 μmol, 1 eq.) and 2,6-lutidine (60 μl, 513 μmol, 3 eq.) were then added, and the mixture was stirred under an atmosphere of dry air at RT for a further 7 d. The reaction mixture was then concentrated to dryness. The residue was suspended in ethyl acetate (10 ml) and filtered. The filtrate was washed with water (5 ml) and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Reprosil C18 column, 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). The brown solid obtained in this manner was decolorized by filtration through a small silica gel cartridge using a mobile phase mixture of cyclohexane and ethyl acetate (2:1) and then lyophilized. The product was obtained as a solid (10.8 mg, 15% of theory).

Workup

  1. stirringthe mixture was stirred under an atmosphere of dry air at RT for a further 7 d
  2. concentrationThe reaction mixture was then concentrated to dryness
  3. filtrationfiltered
  4. washThe filtrate was washed with water (5 ml) and saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC (Reprosil C18 column, 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)
  9. customThe brown solid obtained in this manner
  10. filtrationwas decolorized by filtration through a small silica gel cartridge
  11. additiona mobile phase mixture of cyclohexane and ethyl acetate (2:1)
  12. customThe product was obtained as a solid (10.8 mg, 15% of theory)

Sources & evidence

ORD record
ord-9d68f23150f346939dfe5a186f75a953
Source dataset
uspto-grants-2013_10
Patent number
US08569314B2

Reaction notes

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