Cesium carbonate → 1-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amine

HRID 1662271Notes

Reaction equation

HRID 1662271 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH:25]4[CH2:27][CH2:26]4)[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:4][N:3]=1.[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC.CCO.O>[CH:25]1([C:21]2[CH:20]=[C:19]([C:8]3([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([C:32]5[CH:33]=[N:28][CH:29]=[N:30][CH:31]=5)[CH:7]=4)[C:16]4[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=4)[C:10]([NH2:18])=[N:9]3)[CH:24]=[CH:23][N:22]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 585794871-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine

Product 1

HCID 462030761-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amineYield 50.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
150 °C

Procedure

1-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (92 mg, 0.22 mmol), 5-pyrimidinylboronic acid (35.0 mg, 0.28 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (8.87 mg, 10.87 μmol), cesium carbonate (0.052 mL, 0.65 mmol) and DME:EtOH:water (6:3:1) (3.00 mL) were put in a microwave vial and heated at 150° C. in a microwave reactor for 20 min. The mixture was filtered through a syringe filter and purified by prep-HPLC. The desired fractions were pooled and concentrated in vacuo. The residue was redissolved in acetonitrile and water was added. The mixture was freeze dried to give the title compound (46.9 mg, 47%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.33 (s, 2 H) 9.24 (s, 1 H) 8.67 (d, 1 H) 8.29 (d, 1 H) 7.96 (d, 1 H) 7.87 (d, 1 H) 7.58 (td, 1 H) 7.46 (dd, 1 H) 7.31 (dd, 1 H) 7.21 (d, 1 H) 7.03 (dd, 1 H) 6.79 (br. s., 2 H) 1.96-2.07 (m, 1 H) 0.80-0.96 (m, 4 H); MS (ES+) m/z 423 [M+1]+.

Workup

  1. filtrationThe mixture was filtered through a syringe
  2. filtrationfilter
  3. custompurified by prep-HPLC
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in acetonitrile
  6. additionwater was added
  7. customdried

Sources & evidence

ORD record
ord-b12ebb92d9a94f568f099d553007cbd9
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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