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1-Bromo-4-fluorobenzene → 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one

HRID 41200
Notes
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Reaction equation

HRID 41200 reaction equation
[N:1]1([C:7]([C:9]2[CH:10]=[C:11]3[C:16](=[C:17]([CH:19]4[CH2:23][CH2:22][CH2:21][NH:20]4)[CH:18]=2)[O:15][C:14]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:13][C:12]3=[O:30])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1.Br[C:57]1[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(O[Pd]OC(=O)C)(=O)C>[F:63][C:60]1[CH:61]=[CH:62][C:57]([N:20]2[CH2:21][CH2:22][CH2:23][CH:19]2[C:17]2[CH:18]=[C:9]([C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:8])[CH:10]=[C:11]3[C:16]=2[O:15][C:14]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)=[CH:13][C:12]3=[O:30])=[CH:58][CH:59]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 10796Cesium carbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 866724156-(morpholine-4-carbonyl)-2-morpholino-8-(pyrrolidin-2-yl)-4H-chromen-4-one

Product 1

HCID 866724248-(1-(4-fluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one
Yield 46%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Diacetoxypalladium (6.79 mg, 0.03 mmol) was added to a stirred mixture of 6-(morpholine-4-carbonyl)-2-morpholino-8-(pyrrolidin-2-yl)-4H-chromen-4-one (250 mg, 0.60 mmol), biphenyl-2-yldicyclohexylphosphine (21 mg, 0.06 mmol), 1-bromo-4-fluorobenzene (0.083 ml, 0.76 mmol) and cesium carbonate (296 mg, 0.91 mmol) dissolved in 1,4-dioxane (5 mL). The resulting suspension was degassed with argon and then stirred at 100° C. for 15 h. The reaction mixture was purified by preparative HPLC. The fractions containing the desired compound were evaporated to dryness to afford 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (140 mg, 46%) as a gum.

Workup

  1. customThe resulting suspension was degassed with argon
  2. customThe reaction mixture was purified by preparative HPLC
  3. additionThe fractions containing the desired compound
  4. customwere evaporated to dryness

Sources & evidence

ORD record
ord-8a99fb9e15b94638bc13434adb44e97e
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08530470B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes