Cesium carbonate → HCID 71584845, compound

HRID 1430565Notes

Reaction equation

HRID 1430565 reaction equation
[S:1]1[CH:5]=[C:4]([NH:6][C:7]([NH:9][C:10]2[CH:15]=[C:14]([C:16]3[C:17](=[O:29])[N:18]([CH2:27][CH3:28])[C:19]4[C:24]([CH:25]=3)=[CH:23][N:22]=[C:21](Cl)[CH:20]=4)[C:13]([CH3:30])=[CH:12][C:11]=2[F:31])=[O:8])[C:3]2[CH:32]=[CH:33][CH:34]=[CH:35][C:2]1=2.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:42][N:43]([CH3:47])[C:44]([NH2:46])=[O:45].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>O1CCOCC1.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]>[S:1]1[CH:5]=[C:4]([NH:6][C:7](=[O:8])[NH:9][C:10]2[C:11]([F:31])=[CH:12][C:13]([CH3:30])=[C:14]([C:16]3[C:17](=[O:29])[N:18]([CH2:27][CH3:28])[C:19]4[C:24]([CH:25]=3)=[CH:23][N:22]=[C:21]([NH:46][C:44](=[O:45])[N:43]([CH3:47])[CH3:42])[CH:20]=4)[CH:15]=2)[C:3]2[CH:32]=[CH:33][CH:34]=[CH:35][C:2]1=2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86713692HCID 86713692, compound

Product 1

HCID 71584845HCID 71584845, compoundYield 9.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 1-(benzo[b]thiophen-3-yl)-3-(5-(7-chloro-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)urea (0.23 g, 0.454 mmol), Cs2CO3 (0.443 g, 1.361 mmol), N,N-dimethylurea (0.200 g, 2.268 mmol) and Xantphos (0.079 g, 0.136 mmol) in dioxane (10 mL) was sparged with Ar, treated with Pd2(dba)3 (0.062 g, 0.068 mmol), sparged again with Ar and heated at 100° C. overnight. The mixture was cooled to RT, the solids removed via filtration and rinsed with water and EtOAc. The layers of the filtrate were separated, the organic layer washed with brine, dried over Na2SO4 and concentrated to dryness. The material was treated with DCM, the solid removed via filtration and the filtrate purified via silica gel chromatography (EtOAc/Hex) to afford 3-(3-(5-(3-(benzo[b]thiophen-3-yl)ureido)-4-fluoro-2-methylphenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)-1,1-dimethylurea (25 mg, 9% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.34 (s, 1H), 9.13 (s, 1H), 8.79 (s, 1H), 8.60 (s, 1H), 8.03 (d, J=8.4 Hz, 1H), 7.97 (s, 1H), 7.91 (d, J=8.0 Hz, 1H), 7.83 (m, 2H), 7.62 (s, 1H), 7.45-7.40 (m, 1H), 7.36 (t, J=7.5 Hz, 1H), 7.15 (d, J=12.3 Hz, 1H), 4.14 (d, J=8.0 Hz, 2H), 2.93 (s, 3H), 1.20 (m, 3H); MS (ESI) m/z: 559.2 [M+H]+.

Workup

  1. customwas sparged with Ar
  2. customsparged again with Ar
  3. temperatureThe mixture was cooled to RT
  4. customthe solids removed via filtration
  5. washrinsed with water and EtOAc
  6. customThe layers of the filtrate were separated
  7. washthe organic layer washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated to dryness
  10. additionThe material was treated with DCM
  11. customthe solid removed via filtration
  12. customthe filtrate purified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-50547b2ae77b4b62a825e4960931cf41
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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