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

HRID 41200Notes

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

Participants

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

customThe resulting suspension was degassed with argon
customThe reaction mixture was purified by preparative HPLC
additionThe fractions containing the desired compound
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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