Chloride → 6-(6-aminopyridin-3-yl)-N4-{4-[(2-methylpyridin-4-yl)oxy]phenyl}pyrimidine-2,4-diamine

HRID 729983Notes

Reaction equation

HRID 729983 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([CH3:23])[CH:18]=3)=[CH:12][CH:11]=2)[CH:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][N:26]=1.C([O-])([O-])=O.[Na+].[Na+].[Cl-]>CN(C=O)C>[NH3:5].[NH2:24][C:25]1[N:26]=[CH:27][C:28]([C:2]2[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]4[CH:22]=[CH:21][N:20]=[C:19]([CH3:23])[CH:18]=4)=[CH:12][CH:11]=3)[CH:3]=2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 312ChlorideHCID 10340Sodium CarbonateHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 57833579HCID 57833579, compound

Product 2

HCID 222AmmoniaYield 5%HCID 118449996-(6-aminopyridin-3-yl)-N4-{4-[(2-methylpyridin-4-yl)oxy]phenyl}pyrimidine-2,4-diamineYield 114%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 6-chloro-N4-(4-{[2-methylpyridin-4-yl]oxy}phenyl)pyrimidine-2,4-diamine (2.0 g, 6.1 mmol) and 2-Amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.6 g, 7.3 mmol) in DMF (30 mL) was added aqueous Na2CO3 (2 M, 9.0 mL) and 1,1′-bis(diphenylphosphino)ferrocenepalladium (It) chloride (223 mg, 0.3 mmol). The resulting mixture was degassed for 10 min before it was heated at 80° C. overnight. The resulting mixture was cooled to rt before it was concentrated under vacuo and dissolved in EtOAc. The resulting mixture was washed with water and brine and the organic layer was dried over Na2SO4. Removal of the solvent under vacuo gave the crude material, which was purified with 40 M biotage eluting with 100% EtOAc first and then with 95% CH2Cl2 and 5% 2 N ammonia in MeOH to provide the title compound as an off-white solid (1340 mg, 57%): 1H NMR (DMSO-d6): δ 9.20 (s, 1H), 8.51 (dd, 1H), 8.27 (d, 1H), 7.81-7.88 (m, 3H), 7.03-7.06 (m, 2H), 6.72 (d, 1H), 6.68 (dd, 1H), 6.47 (dd, 1H), 6.33 (s, 1H), 6.32 (s, 2H), 6.23 (s, 2H), 2.39 (s, 3H) ppm; MS ES 386 (M+H)+, RT=1.06 min.

Workup

  1. customThe resulting mixture was degassed for 10 min before it
  2. temperatureThe resulting mixture was cooled to rt before it
  3. concentrationwas concentrated under vacuo
  4. dissolutiondissolved in EtOAc
  5. washThe resulting mixture was washed with water and brine
  6. dry with materialthe organic layer was dried over Na2SO4
  7. customRemoval of the solvent under vacuo
  8. customgave the crude material, which
  9. customwas purified with 40 M biotage
  10. washeluting with 100% EtOAc first

Sources & evidence

ORD record
ord-9e5bcc86497a4fff95ec6e836a2b9812
Source dataset
uspto-grants-2009_09
Patent number
US07582646B2

Reaction notes

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