2,6-Lutidine → HCID 46700784, compound

HRID 1046840Notes

Reaction equation

HRID 1046840 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])=[C:5]([S:32]([CH3:35])(=[O:34])=[O:33])[CH:4]=1)#[N:2].[F:36][C:37]([F:48])([F:47])[C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][CH:43]=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: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:42]3[CH:41]=[CH:40][CH:39]=[C:38]([C:37]([F:48])([F:47])[F:36])[CH:43]=3)[C:11]([CH3:29])=[C:10]2[C:30]#[N:31])=[C:5]([S:32]([CH3:35])(=[O:34])=[O:33])[CH:4]=1)#[N:2]

Participants

9

Reactant 4

HCID 79372,6-Lutidine2×HCID 8471TriethylamineHCID 27343883-(Trifluoromethyl)phenylboronic acid2×HCID 135964510HCID 135964510, compound

Product 1

HCID 46700784HCID 46700784, compound

Reagents, catalysts & solvents 4

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

Procedure

Under an atmosphere of argon protective gas, (rac)-7-[4-cyano-2-(methylsulfonyl)phenyl]-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 (600 mg, 1.2 mmol) was stirred in abs. dichloromethane (50 ml) with molecular sieve (0.5 g, 4 Å) for 15 min 3-(Trifluoromethyl)phenylboronic acid (704 mg, 3.7 mmol, 3 eq.) was added together with anhydrous copper(II) acetate (673 mg, 3.7 mmol, 3 eq.). Abs. pyridine (60 ml) and triethylamine (571 μl, 3.7 mmol, 3 eq.) were then added, and the mixture was stirred for 12 h. 2,6-Lutidine (864 μl, 7.4 mmol, 6 eq.) was then added, and the reaction mixture initially stirred under an atmosphere of dry air for 12 h and then left under an atmosphere of argon for 3 d. More 3-(trifluoromethyl)phenylboronic acid (235 mg, 1.2 mmol, 1 eq.), anhydrous copper(II) acetate (225 mg, 1.2 mmol, 1 eq.), 2,6-lutidine (432 μl, 3.7 mmol, 3 eq.) and a catalytic amount (spatula tip) of activated copper were then added, and the mixture was stirred under an atmosphere of dry air for 5 d. The reaction mixture was then concentrated to dryness, and the residue was applied to silica gel using dichloromethane (˜50 ml) to silica gel and purified by flash chromatography (silica gel; mobile phase: cyclohexane/ethyl acetate 1:2). The product was obtained as a solid (102 mg, 13.1% of theory).

Workup

  1. stirringthe reaction mixture initially stirred under an atmosphere of dry air for 12 h
  2. waitleft under an atmosphere of argon for 3 d
  3. stirringthe mixture was stirred under an atmosphere of dry air for 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 (102 mg, 13.1% of theory)

Sources & evidence

ORD record
ord-abb14d35056044888c86c74c4fc1d14a
Source dataset
uspto-grants-2013_10
Patent number
US08569314B2

Reaction notes

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