Nitrogen → HCID 58318519, compound

HRID 1944269Notes

Reaction equation

HRID 1944269 reaction equation
N#N.Br[C:4]1[S:8][C:7]([CH2:9][C:10]#[N:11])=[CH:6][CH:5]=1.CC1(C)C(C)(C)OB([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[NH2:26])O1>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:4]1[S:8][C:7]([CH2:9][C:10]#[N:11])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 947NitrogenHCID 8188762-(5-bromothiophen-2-yl)acetonitrileHCID 27346522-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 58318519HCID 58318519, compoundYield 78.4%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
90 °C

Procedure

(The following reaction is done in an oxygenfree N2 atmosphere.) Dissolve tetrakis-(triphenylphosphine)-palladium(0) (29 mg, 2.5 mol %) and nitrile (83) (101 mg, 0.50 mmol) in DME (3.7 mL). The reaction mixture is degassed 5 times and flooded with N2 again. Add 2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenylamine (84) (120 mg, 0.55 mmol), rinse with DME (0.5 mL), add aqu. 1M NaHCO3, degas again (5 times) and stir the reaction solution 2 h at 90° C. (reflux). After cooling to rt partition the reaction mixture between EtOAc and brine (1+1) and extract the separated aqueous layer 3 times with EtOAc. Wash combined organic layer with brine and dry with Na2SO4. Remove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60PF, CyH/EtOAc 2+1) to obtain [5-(2-amino-phenyl)-thiophen-2-yl]-acetonitrile (85) as a brownish oil (84 mg, 78%). 1H NMR (400 MHz, CDCl3): 3.89 (br.s, 2H); 5.20-6.50 (br.s, 2H); 6.92 (t, 1H; J=7.6 Hz); 6.95-7.00 (m, 1H); 6.99 (d, 1H; J=3.8 Hz); 7.11 (d, 1H; J=3.8 Hz); 7.21 (dd, 1H; J1=7.6 Hz, J2=1.3 Hz); 7.27 (dd, 1H; J1=7.6 Hz, J2=1.3 Hz).

Workup

  1. custom(The following reaction
  2. customThe reaction mixture is degassed 5 times
  3. additionadd aqu
  4. custom1M NaHCO3, degas again (5 times)
  5. temperature(reflux)
  6. temperatureAfter cooling to rt
  7. custompartition the reaction mixture between EtOAc and brine (1+1)
  8. extractionextract the separated aqueous layer 3 times with EtOAc
  9. washWash
  10. dry with materialdry with Na2SO4
  11. customRemove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60PF, CyH/EtOAc 2+1)

Sources & evidence

ORD record
ord-96c1dc9033e54f8ca827dc3f42039d57
Source dataset
uspto-grants-2013_03
Patent number
US08394835B2

Reaction notes

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