Dimethylformamide → HCID 69426563, compound

HRID 456976Notes

Reaction equation

HRID 456976 reaction equation
[Br:1][C:2]1(N)[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:16])[CH:8]=2)[NH:3]1.[CH3:18][N:19](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1([C:18]#[N:19])[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:16])[CH:8]=2)[NH:3]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 69425062HCID 69425062, compound

Product 1

HCID 69426563HCID 69426563, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
140 °C

Procedure

2-Bromo-6-chloro-4-(trifluoromethyl)-quinolineamine (5, 476 mg, 1.46 mmol) was dissolved in anhydrous DMF (5 mL) under N2. Zn(CN)2 (103 mg, 0.88 mmol) was added and the solution was degassed with a stream of N2. Pd(PPh3)4 (34 mg, 0.029 mmol) was added and the solution was degassed again and then heated to 140° C. The reaction was complete by TLC after 80 min. The reaction mixture was cooled to rt and diluted with EtOAc (100 mL), The organic phase was washed with H2O (2×20 mL) and brine (1×20 mL) then dried over MgSO4. Concentration and chromatography (SiO2, 40 g, 10% EtOAc-hexane) provided the desired material 6 as a yellow crystalline solid (202 mg, 51%). mp 188° C. Rf 0.34 (10% Ethyl acetate-hexane). 1H NMR (CDCl3, 300 MHz) δ 7.95 (d, J=8.8 Hz, 1H), 7.94 (m, 1H), 7.52 (dd, J=2.2, 8.8 Hz, 1H), 5.34 (br s, 2H, NH2); 19F NMR (CDCl3, 300 MHz) δ−54.51; 13C NMR (CDCl3, 75 MHz) δ140.21, 139.00, 138.39, 132.27, 128.25, 126.65, 126.10, 122.98, 121.90, 121.84, 114.43; IR (KBr) υmax 3485, 3410, 3386, 2230, 1650, 1639, 1574, 1492, 1430, 1352, 1322, 1221, 1158, 1130, 1121, 1095, 975, 822 cm−1.

Workup

  1. customthe solution was degassed with a stream of N2
  2. customthe solution was degassed again
  3. temperatureThe reaction mixture was cooled to rt
  4. additiondiluted with EtOAc (100 mL)
  5. washThe organic phase was washed with H2O (2×20 mL) and brine (1×20 mL)
  6. dry with materialthen dried over MgSO4
  7. concentrationConcentration and chromatography (SiO2, 40 g, 10% EtOAc-hexane)

Sources & evidence

ORD record
ord-1993cff76f8740bea01876f6b68ab69d
Source dataset
uspto-grants-2007_03
Patent number
US07186830B2

Reaction notes

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