Toluene → 6-[2-(2,4-Difluorophenyl)ethynyl]-3-nitro-pyridin-2-amine

HRID 2065798Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:19]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28])#[CH:20].C1(C)C=CC=CC=1>C(#N)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:28][C:22]1[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:21]=1[C:19]#[C:20][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 32.5 °C

Procedure

6-Chloro-3-nitro-pyridin-2-ylamine (16.2 kg, 93.3 mol), acetonitrile (130.8 L), cuprous iodide (0.18 kg, 1.0 mol), and bis(triphenylphosphine)palladium (II) chloride (0.66 kg, 0.9 mol) are combined under a nitrogen atmosphere at 20-25° C. with stirring. Triethylamine (19.7 L, 141.3 mol) is added and the mixture is heated to 30-35° C. A solution of 1-ethynyl-2,4-difluoro-benzene (18.0 kg, 130.3 mol) in acetonitrile (32.6 L) is added under a nitrogen atmosphere at 30-35° C. The mixture is stirred at 15-25° C. for 2-4 h. Toluene (80.0 L) is added and the mixture is stirred for 0.5-1 h, then cooled to 0-5° C. and stirred for 2-4 h. The reaction mixture is centrifuged and the filter cake is rinsed with toluene (2×64 L) and water (2×32.4 L). The solids are dried under reduced pressure below 50° C. to furnish the title compound as a yellow solid (21.7 kg, 83%).

Workup

customare combined under a nitrogen atmosphere at 20-25° C.
stirringThe mixture is stirred at 15-25° C. for 2-4 h
stirringthe mixture is stirred for 0.5-1 h
temperaturecooled to 0-5° C.
stirringstirred for 2-4 h
washthe filter cake is rinsed with toluene (2×64 L) and water (2×32.4 L)
customThe solids are dried under reduced pressure below 50° C.

Sources & evidence

ORD record: ord-0a69bcf1a237493cabe6d7a9e5f7cabe
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288548B2

Reaction notes

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