Pyridine → HCID 58032635, compound

HRID 2200995Notes

Reaction equation

HRID 2200995 reaction equation
[C:1]([C:4]1[CH:9]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[N:8]2[N:18]=[N:19][N:20]=[C:7]2[NH:6][C:5]=1[CH3:21])(=[O:3])[CH3:2].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.N1C=CC=CC=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[C:1]([C:4]1[CH:9]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[N:8]2[N:18]=[N:19][N:20]=[C:7]2[N:6]([C:28]2[CH:27]=[CH:26][CH:25]=[C:24]([C:23]([F:34])([F:33])[F:22])[CH:29]=2)[C:5]=1[CH3:21])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 8471Triethylamine2×HCID 27343883-(Trifluoromethyl)phenylboronic acid2×HCID 136133143HCID 136133143, compound

Product 1

HCID 58032635HCID 58032635, compound

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

Under an atmosphere of argon protective gas, (rac)-4-(6-acetyl-5-methyl-4,7-dihydrotetrazolo[1,5-a]pyrimidin-7-yl)benzonitrile (50 mg, 178 μmol) was stirred in abs. dichloromethane (3 ml) with molecular sieve (0.5 g, 4 Å) for 1 h. 3-(Trifluoromethyl)phenylboronic acid (101.6 mg, 535 μmol, 3 eq.), anhydrous copper(II) acetate (97.2 mg, 535 μmol, 3 eq.), abs. pyridine (115 μl, 1.43 mmol, 8 eq.) and triethylamine (54.2 mg, 535 μmol, 3 eq.) were then added, and the mixture was stirred at RT for 12 h. More molecular sieve (0.5 g, 4 Å), 3-(trifluoromethyl)phenylboronic acid (33 mg, 178 μmol, 1 eq.), anhydrous copper(II) acetate (32 mg, 178 μmol, 1 eq.), triethylamine (18.1 mg, 178 μmol, 1 eq.) and abs. pyridine (57.5 μl, 715 μmol, 4 eq.) were then added, and the mixture was stirred at RT for a further 12 h. The reaction mixture was then filtered through kieselguhr, the filter residue was washed with dichloromethane and methanol and the filtrate was concentrated to dryness. The residue was purified by preparative HPLC (Gromsil C18 column, 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). The product was obtained as a colorless solid (14.6 mg, 19% of theory).

Workup

  1. stirringthe mixture was stirred at RT for a further 12 h
  2. filtrationThe reaction mixture was then filtered through kieselguhr
  3. washthe filter residue was washed with dichloromethane and methanol
  4. concentrationthe filtrate was concentrated to dryness
  5. customThe residue was purified by preparative HPLC (Gromsil C18 column, 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)
  6. customThe product was obtained as a colorless solid (14.6 mg, 19% of theory)

Sources & evidence

ORD record
ord-e15ad53be0604103be393a18dd2dde16
Source dataset
uspto-grants-2016_06
Patent number
US09359362B2

Reaction notes

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