Tetrahydrofuran → 5-(6-Chloro-2-morpholin-4-ylpyrimidin-4-yl)pyridin-2-ylamine

HRID 1043801

Reaction equation

HRID 1043801 reaction equation
C1COCC1.C([O-])([O-])=O.[Na+].[Na+].Cl[C:13]1[CH:18]=[C:17]([Cl:19])[N:16]=[C:15]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:14]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=2)O1>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].O.CCOC(C)=O>[Cl:19][C:17]1[N:16]=[C:15]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:14]=[C:13]([C:34]2[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=2)[CH:18]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholine

Product 1

HCID 595075305-(6-Chloro-2-morpholin-4-ylpyrimidin-4-yl)pyridin-2-ylamineYield 44.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

THF (130 mL) and aq. Na2CO3 (2M, 40 mL, 80 mmol) were added to a glass pressure vessel containing 4,6-dichloro-2-morpholinopyrimidine (prepared as in Method 22; 4.5 g, 19.2 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (4.7 g, 21.2 mmol). The resulting mixture was stirred and sparged with argon for 1-2 minutes. The catalyst, dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (1.26 g, 1.54 mmol), was then added in one portion. After sealing the reaction vessel, the reaction was heated at 85° C. for 1 hour with stirring. Upon cooling to RT, the THF was removed under reduced pressure to leave a viscous residue. EtOAc (450 mL) and water (50 mL) were added. After vigorously stirring for 1-2 minutes, the solids were filtered off and washed with EtOAc (100 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (100 mL). The combined organic layers were washed with saturated NaCl solution (1×50 mL), dried with Na2SO4, filtered and evaporated under reduced pressure. The crude material was further purified by silica gel chromatography to give 5-(6-chloro-2-morpholin-4-yl-pyrimidin-4-yl)-pyridin-2-ylamine (2.48 g, 44%). LC/MS (m/z): 292.1 (MH+), Rt 2.06 minutes.

Workup

  1. customsparged with argon for 1-2 minutes
  2. stirringwith stirring
  3. temperatureUpon cooling to RT
  4. customthe THF was removed under reduced pressure
  5. customto leave a viscous residue
  6. stirringAfter vigorously stirring for 1-2 minutes
  7. filtrationthe solids were filtered off
  8. washwashed with EtOAc (100 mL)
  9. customThe organic layer was separated
  10. extractionthe aqueous layer was extracted with EtOAc (100 mL)
  11. washThe combined organic layers were washed with saturated NaCl solution (1×50 mL)
  12. dry with materialdried with Na2SO4
  13. filtrationfiltered
  14. customevaporated under reduced pressure
  15. customThe crude material was further purified by silica gel chromatography

Sources & evidence

ORD record
ord-1b334ca990f84f09b9942467c39315eb
Source dataset
uspto-grants-2013_10
Patent number
US08563549B2

Linked notes

Loading…