Triphenylphosphine → HCID 53329539, compound

HRID 1029025Notes

Reaction equation

HRID 1029025 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]([NH2:26])=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][CH:11]=3)[CH2:3][CH2:2]1.[Cl:27][C:28]1[C:29](I)=[C:30]([C:34]([N:36]2[CH2:40][CH2:39][CH2:38][CH2:37]2)=[O:35])[CH:31]=[CH:32][CH:33]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:26][C:8]1[C:7]([N:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:29]3[C:28]([Cl:27])=[CH:33][CH:32]=[CH:31][C:30]=3[C:34]([N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)=[O:35])[CH:14]=2)[N:9]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 67324196HCID 67324196, compoundHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 53329539HCID 53329539, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
60 °C

Procedure

A vial was charged with 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (710 mg, 2.000 mmol, prepared as in Example 2, Step 1-2), (3-chloro-2-iodophenyl)(pyrrolidin-1-yl)methanone (671 mg, 2 mmol), Pd(OAc)2 (22.45 mg, 0.100 mmol), triphenylphosphine (52.5 mg, 0.200 mmol) and potassium phosphate (0.331 mL, 4.00 mmol). The vial was evacuated and backfilled with nitrogen gas 3×. ACN (8 mL) and water (2 mL) were added and the reaction mixture was heated to 60° C. overnight in an oil bath. The product precipitated out of solution and was filtered off, dissolved in DCM/MeOH, washed with water and dried over MgSO4. The solvent was removed and the solid was dried under vacuum at 50° C. This material was further purified by preparative HPLC (10-100%; water with 0.1% TFA/CH3CN, 11 min). The obtained product was eluted on an SCX cartridge with MeOH followed by 2M NH3 in MeOH. The basic fraction was concentrated to afford the titled compound as a light-yellow solid. MS (ESI, pos. ion) m/z: 437 (M+1).

Workup

  1. customThe vial was evacuated
  2. additionACN (8 mL) and water (2 mL) were added
  3. customThe product precipitated out of solution
  4. filtrationwas filtered off
  5. dissolutiondissolved in DCM/MeOH
  6. washwashed with water
  7. dry with materialdried over MgSO4
  8. customThe solvent was removed
  9. customthe solid was dried under vacuum at 50° C
  10. customThis material was further purified by preparative HPLC (10-100%; water with 0.1% TFA/CH3CN, 11 min)
  11. washThe obtained product was eluted on an SCX cartridge with MeOH
  12. concentrationThe basic fraction was concentrated

Sources & evidence

ORD record
ord-3aa8456a0ead4d28962da1f636aa128d
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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