Trifluoroacetic acid → (2-(2-Amino-3-(2-ethylmorpholino)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone

HRID 1028973Notes

Reaction equation

HRID 1028973 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:10].[CH2:16]([CH:18]1[CH2:23][N:22]([C:24]2[C:25]([NH:43]CC3C=CC(OC)=CC=3)=[N:26][C:27]3[C:32]([CH:33]=2)=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=3)[CH2:21][CH2:20][O:19]1)[CH3:17].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(O)(C(F)(F)F)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:43][C:25]1[C:24]([N:22]2[CH2:21][CH2:20][O:19][CH:18]([CH2:16][CH3:17])[CH2:23]2)=[CH:33][C:32]2[C:27](=[CH:28][CH:29]=[C:30]([C:2]3[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=3[C:9]([N:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)=[O:10])[CH:31]=2)[N:26]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 62657Potassium Phosphate, TribasicHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 665791491-(2-Bromo-3-methylbenzoyl)pyrrolidineHCID 712530353-(2-ethylmorpholino)-N-(4-methoxybenzyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 53328995(2-(2-Amino-3-(2-ethylmorpholino)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
140 °C

Procedure

A mixture of (2-bromo-3-methylphenyl)(pyrrolidin-1-yl)methanone (0.256 g, 0.953 mmol), 3-(2-ethylmorpholino)-N-(4-methoxybenzyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.16 g, 0.318 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (0.030 g, 0.064 mmol), potassium phosphate, anhydrous (0.132 mL, 1.589 mmol), and Pd2(dba)3 (0.029 g, 0.032 mmol) was purged with N2 followed by the addition of degassed dioxane (2 mL) and degassed water (1.0 mL). The resulting mixture was heated in microwave at 140° C. for 12 min. The reaction went to completion and it was filtered, concentrated, and chromatographed on silica gel using 0-5% MeOH/DCM to afford a light yellow oil. To this product was added TFA (15 mL, 195 mmol) and heated at 70° C. for 18 h until the starting material was consumed. The mixture was concentrated and chromatographed on silica gel using 0-5% 2M NH3 in MeOH/DCM to afford a light yellow solid as (2-(2-amino-3-(2-ethylmorpholino)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone. MS (ESI, pos. ion) m/z: 445 (M+1).

Workup

  1. customwas purged with N2
  2. additionfollowed by the addition of degassed dioxane (2 mL)
  3. customdegassed water (1.0 mL)
  4. filtrationwas filtered
  5. concentrationconcentrated
  6. customchromatographed on silica gel using 0-5% MeOH/DCM
  7. customto afford a light yellow oil
  8. temperatureheated at 70° C. for 18 h until the starting material
  9. customwas consumed
  10. concentrationThe mixture was concentrated
  11. customchromatographed on silica gel using 0-5% 2M NH3 in MeOH/DCM

Sources & evidence

ORD record
ord-96cf7a274832449ebd9ac3326125e764
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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