Cesium carbonate → HCID 59618307, compound

HRID 449932Notes

Reaction equation

HRID 449932 reaction equation
[Cl:1][C:2]1[CH:18]=[C:17]([Cl:19])[CH:16]=[C:15]([Cl:20])[C:3]=1[C:4]([NH:6][C:7]1[C:12]([F:13])=[CH:11][N:10]=[C:9](Cl)[CH:8]=1)=[O:5].[CH:21]1([C:24]([NH2:26])=[O:25])[CH2:23][CH2:22]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[Cl:1][C:2]1[CH:18]=[C:17]([Cl:19])[CH:16]=[C:15]([Cl:20])[C:3]=1[C:4]([NH:6][C:7]1[C:12]([F:13])=[CH:11][N:10]=[C:9]([NH:26][C:24]([CH:21]2[CH2:23][CH2:22]2)=[O:25])[CH:8]=1)=[O:5]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86648966HCID 86648966, compound

Product 1

HCID 59618307HCID 59618307, compoundYield 9.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a microwave tube was added 2,4,6-trichloro-N-(2-chloro-5-fluoropyridin-4-yl)benzamide (71 mg, 0.20 mmol), cyclopropanecarboxamide (42.8 mg, 0.50 mmol), Pd2(dba)3 (18 mg, 0.020 mmol), XantPhos (14 mg, 0.025 mmol), Cs2CO3 (197 mg, 0.60 mmol) and dioxane (1.5 mL). The mixture was degassed with N2 for 2 min. The resulting mixture was irradiated in a microwave reactor at 140° C. for 35 min and then cooled to room temperature. The mixture was filtered through Celite and concentrated under reduced pressure. The residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give the desired product (7.5 mg, yield: 9.2%). 1H NMR (DMSO-d6, 400 MHz): δ 11.08 (s, 1H), 10.83 (d, 1H), 9.00 (s, 1H), 8.32 (s, 1H), 7.82 (s, 2H), 1.98 (d, J=4.6 Hz, 1H), 0.82 (t, J=6.1 Hz, 4H). LCMS (ESI) m/z: 402.0 [M+H+].

Workup

  1. customThe mixture was degassed with N2 for 2 min
  2. customThe resulting mixture was irradiated in a microwave reactor at 140° C. for 35 min
  3. filtrationThe mixture was filtered through Celite
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

Sources & evidence

ORD record
ord-239efe90061c4774a957d551ba9395e9
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

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