2-(Trimethylstannyl)isonicotinonitrile → 2-(3-(3-Amino-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-1-yl) phenyl)isonicotinonitrile

HRID 1662259Notes

Reaction equation

HRID 1662259 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([O:25][CH3:26])[CH:20]=3)[C:16]3[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.C[Sn](C)(C)[C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][N:36]=1)[C:32]#[N:33]>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.CN(C=O)C>[NH2:18][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[C:8]([C:4]2[CH:3]=[C:2]([C:29]3[CH:30]=[C:31]([CH:34]=[CH:35][N:36]=3)[C:32]#[N:33])[CH:7]=[CH:6][CH:5]=2)([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([O:25][CH3:26])[CH:20]=2)[N:9]=1

Participants

5

Reactant 2

HCID 585794962-(Trimethylstannyl)isonicotinonitrileHCID 585794981-(3-Bromophenyl)-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-3-amine

Product 1

HCID 462024142-(3-(3-Amino-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-1-yl) phenyl)isonicotinonitrileYield 9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

1-(3-Bromophenyl)-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-3-amine (0.200 g, 0.49 mmol), 2-(trimethylstannyl)isonicotinonitrile (0.194 g, 0.73 mmol), tetrakis(triphenylphosphine)palladium(0) (0.056 g, 0.05 mmol) and DMF (4 mL) were put in a microwave vial and heated in a microwave reactor at 110° C. for 20 min, then at 150° C. for 20 min. The reaction mixture was filtered through a syringe filter and purified by preparative HPLC. The desired fractions were pooled and concentrated in vacuo. The residue was partitioned between aqueous sodium bicarbonate (sat.) and ethyl acetate. The aqueous layer was extracted with EtOAc (×2), the combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound (0.018 g, 9%). 1H NMR (500 MHz, DMSO-d6) δ ppm 8.86 (dd, 1 H) 8.40 (t, 1 H) 8.11-8.15 (m, 1 H) 8.04 (d, 1 H) 8.01 (ddd, 1 H) 7.78-7.81 (m, 1 H) 7.66 (d, 1 H) 7.51-7.57 (m, 1 H) 7.42-7.47 (m, 2 H) 7.24-7.31 (m, 1 H) 6.88 (dd, 1 H) 6.59-6.71 (m, 3 H) 3.79 (s, 3 H); MS (ES+) m/z 436 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through a syringe
  2. filtrationfilter
  3. custompurified by preparative HPLC
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between aqueous sodium bicarbonate (sat.) and ethyl acetate
  6. extractionThe aqueous layer was extracted with EtOAc (×2)
  7. dry with materialthe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a581cc2e576405a9ae77887557a1306
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

Loading…