Pyridine → HCID 46840937, compound

HRID 1046837Notes

Reaction equation

HRID 1046837 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]3[N:15]=[C:16]([N:18]4[C:26](=[O:27])[C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[C:19]4=[O:28])[N:17]=[C:13]3[NH:12][C:11]([CH3:29])=[C:10]2[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:5][CH:4]=1)#[N:2].[F:35][C:36]([F:47])([F:46])[C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1.N1C=CC=CC=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[N:14]3[N:15]=[C:16]([N:18]4[C:19](=[O:28])[C:20]5[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=5)[C:26]4=[O:27])[N:17]=[C:13]3[N:12]([C:41]3[CH:40]=[CH:39][CH:38]=[C:37]([C:36]([F:47])([F:46])[F:35])[CH:42]=3)[C:11]([CH3:29])=[C:10]2[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:7][CH:8]=1)#[N:2]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 8471TriethylamineHCID 27343883-(Trifluoromethyl)phenylboronic acid2×HCID 136133144HCID 136133144, compound

Product 1

HCID 46840937HCID 46840937, compound

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

Ethyl 7-(4-cyanophenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-methyl-4,7-dihydro[1,2,4]-triazolo[1,5-a]pyrimidine-6-carboxylate (50 mg, 0.11 mmol), 3-(trifluoromethyl)phenylboronic acid (63 mg, 0.33 mmol, 3 eq.), anhydrous copper(II) acetate (60 mg, 0.33 mmol, 3 eq.) and molecular sieve (50 mg, 4 Å) were initially charged. Under an atmosphere of argon protective gas, abs. dichloromethane (2.5 ml), pyridine (71 μl, 0.88 mmol) and triethylamine (46 μl, 0.33 mmol, 3 eq.) were added. After 12 h of stirring, more 3-(trifluoromethyl)phenylboronic acid (21 mg, 0.11 mmol, 1 eq.), anhydrous copper(II) acetate (20 mg, 0.11 mmol, 1 eq.) and pyridine (36 μl, 0.44 mmol) were added. After a further 24 h of stirring, the mixture was filtered through kieselguhr, the residue was washed with dichloromethane and methanol and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (23.3 mg, 35% of theory).

Workup

  1. stirringAfter a further 24 h of stirring
  2. filtrationthe mixture was filtered through kieselguhr
  3. washthe residue was washed with dichloromethane and methanol
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
  6. customAfter lyophilization, the product was obtained as a solid (23.3 mg, 35% of theory)

Sources & evidence

ORD record
ord-ca97a80651d14be6b1eff309723d7462
Source dataset
uspto-grants-2013_10
Patent number
US08569314B2

Reaction notes

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