2,6-Lutidine → HCID 46841071, compound

HRID 2200939Notes

Reaction equation

HRID 2200939 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]#[N:31])=[CH:5][CH:4]=1)#[N:2].[F:32][C:33]([F:44])([F:43])[C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.C(N(CC)CC)C.N1C(C)=CC=CC=1C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.[Cu].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]([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[N:12]([C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([C:33]([F:44])([F:43])[F:32])[CH:39]=3)[C:11]([CH3:29])=[C:10]2[C:30]#[N:31])=[CH:5][CH:4]=1)#[N:2]

Participants

9

Reactant 4

HCID 79372,6-LutidineHCID 8471Triethylamine2×HCID 27343883-(Trifluoromethyl)phenylboronic acid2×HCID 136355660HCID 136355660, compound

Product 1

HCID 46841071HCID 46841071, compound

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalyst2×HCID 23978CopperCatalystHCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Under an atmosphere of argon protective gas, (rac)-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-carbonitrile (12 g, 29.5 mmol) was stirred in abs. dichloromethane (600 ml) with molecular sieve (20 g, 4 Å) for 1 h. 3-(Trifluoromethyl)phenylboronic acid (16.78 g, 88.4 mmol, 3 eq.) was added together with anhydrous copper(II) acetate (16.05 g, 88.4 mmol, 3 eq.). Abs. pyridine (400 ml) and triethylamine (12.32 ml, 88.4 mmol, 3 eq.) were then added. This mixture was stirred briefly (5 min), more abs. pyridine (440 ml) was then added and the mixture was stirred for 36 h. Since it was subsequently still possible to detect starting material (HPLC), 2,6-lutidine (3.43 ml, 29.6 mmol, 1 eq.) and a catalytic amount (spatula tip) of activated copper were added and the mixture was stirred under an atmosphere of dry air for a further 36 h. More 3-(trifluoromethyl)phenylboronic acid (5.59 g, 29.5 mmol, 1 eq.), anhydrous copper(II) acetate (5.35 g, 29.5 mmol, 1 eq.) and triethylamine (4.11 ml, 29.5 mmol, 1 eq.) were then metered in, and the mixture was then stirred for a further 5 d. The reaction mixture was then concentrated to dryness, and the residue was applied to silica gel using dichloromethane (˜500 ml) and purified by flash chromatography (silica gel; mobile phase: cyclohexane/ethyl acetate 1:2). The product was obtained as a solid (3.07 g, 18.1% of theory).

Workup

  1. stirringthe mixture was stirred for 36 h
  2. stirringthe mixture was stirred under an atmosphere of dry air for a further 36 h
  3. stirringwas then stirred for a further 5 d
  4. concentrationThe reaction mixture was then concentrated to dryness
  5. custompurified by flash chromatography (silica gel; mobile phase: cyclohexane/ethyl acetate 1:2)
  6. customThe product was obtained as a solid (3.07 g, 18.1% of theory)

Sources & evidence

ORD record
ord-a8371c0ce92548d0b9e8bf6c88a32a4f
Source dataset
uspto-grants-2016_06
Patent number
US09359362B2

Reaction notes

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