Sodium Carbonate → 1-(2-(Difluoromethyl)-6-methylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amine

HRID 1662254Notes

Reaction equation

HRID 1662254 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2([C:19]3[CH:24]=[C:23]([CH3:25])[N:22]=[C:21]([CH:26]([F:28])[F:27])[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:29]1[CH:34]=[C:33](B(O)O)[CH:32]=[N:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:28][CH:26]([F:27])[C:21]1[CH:20]=[C:19]([C:8]2([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([C:33]4[CH:34]=[N:29][CH:30]=[N:31][CH:32]=4)[CH:7]=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:24]=[C:23]([CH3:25])[N:22]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 58579503HCID 58579503, compound

Product 1

HCID 462020831-(2-(Difluoromethyl)-6-methylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amineYield 14%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

1-(2-Chloropyridin-4-yl)-1-(2-(difluoromethyl)-6-methylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (400 mg, 0.99 mmol), pyrimidin-5-ylboronic acid (135 mg, 1.09 mmol) and (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (82 mg, 0.10 mmol) were mixed in THF (3 mL). Aqueous sodium carbonate (2M) (1.490 mL, 2.98 mmol) was added and the mixture was heated in a microwave reactor for 40 min at 140° C. The mixture was filtered through a pad of Celite®, eluated with DCM (15 mL) and concentrated in vacuo. Purification by preparative HPLC afforded 60 mg (14%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 9.26 (s, 2 H) 9.25 (s, 1 H) 8.69 (d, 1 H) 7.68 (s, 1 H) 7.50-7.58 (m, 1 H) 7.39 (d, 1 H) 7.35 (s, 1 H) 7.25 (dd, 1 H) 7.22 (s, 1 H) 7.19 (d, 1 H) 6.75-6.42 (t, 1 H) 2.56 (s, 3 H); MS (ES+) m/z 447 [M+1]+.

Workup

  1. filtrationThe mixture was filtered through a pad of Celite®
  2. concentrationconcentrated in vacuo
  3. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-2d86d4d26a5e4f0aaa7b9d7d9166d0b1
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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