2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 5-{2-Fluoro-4-[2-(1-methylethoxy)pyridin-3-yl]phenyl}pyrimidin-2-amine

HRID 1523930Notes

Reaction equation

HRID 1523930 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]([NH2:14])=[N:12][CH:13]=2)=[C:4]([F:15])[CH:3]=1.[CH:16]([O:19][C:20]1[C:25](B(O)O)=[CH:24][CH:23]=[CH:22][N:21]=1)([CH3:18])[CH3:17].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>>[F:15][C:4]1[CH:3]=[C:2]([C:25]2[C:20]([O:19][CH:16]([CH3:18])[CH3:17])=[N:21][CH:22]=[CH:23][CH:24]=2)[CH:7]=[CH:6][C:5]=1[C:8]1[CH:9]=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1

Participants

4

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 467393182-Isopropoxypyridine-3-boronic acidHCID 790224125-(4-Chloro-2-fluorophenyl)pyrimidin-2-amine

Product 1

HCID 903127955-{2-Fluoro-4-[2-(1-methylethoxy)pyridin-3-yl]phenyl}pyrimidin-2-amineYield 49%

Procedure

To a microwave vial the following were added 5-(4-chloro-2-fluorophenyl)-pyrimidin-2-amine (50 mg, 0.22 mmol), (2-isopropoxypyridin-3-yl)boronic acid (51 mg, 0.28 mmol) and X-Phos precatalyst (4 mg, 0.005 mmol). The vial was flushed with nitrogen and then THF (0.5 mL) and 0.5 M K3PO4 (0.9 mL) were added. Both THF and the K3PO4 solution were sparged separately for 30 min prior to use. The resulting biphasic mixture was stirred at rt overnight. The reaction mixture was then poured into sat. NaHCO3 (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (1×50 mL) and brine (1×50 mL), dried (Na2SO4) and concentrated to dryness. The crude product was purified by HPLC to give the title compound (35 mg, 48%). MS (ESI): mass calcd. for C18H17FN4O, 324.14; m/z found, 325.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=1.4, 2H), 8.21-8.13 (m, 1H), 7.68-7.60 (m, 1H), 7.50-7.36 (m, 3H), 6.99-6.91 (m, 1H), 5.51-5.37 (m, 1H), 5.15 (s, 2H), 1.38 (d, J=6.2, 6H).

Workup

  1. customThe vial was flushed with nitrogen
  2. additionTHF (0.5 mL) and 0.5 M K3PO4 (0.9 mL) were added
  3. customBoth THF and the K3PO4 solution were sparged separately for 30 min
  4. additionThe reaction mixture was then poured into sat. NaHCO3 (50 mL)
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. washThe combined organic extracts were washed with water (1×50 mL) and brine (1×50 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-2cc50f10c8ce45af97302f3e4755262b
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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