Acetamide → HCID 71735419, compound

HRID 715143Notes

Reaction equation

HRID 715143 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:14]=[CH:15][C:16]([F:29])=[C:17]([NH:19][C:20]([NH:22][CH2:23][CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:21])[CH:18]=3)[C:8]([CH3:12])=[N:9]2)=[CH:4][N:3]=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+].[C:78]([NH2:81])(=[O:80])[CH3:79]>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]>[CH3:26][C:25]([CH3:28])([CH3:27])[CH2:24][CH2:23][NH:22][C:20](=[O:21])[NH:19][C:17]1[CH:18]=[C:13]([C:7]2[C:8]([CH3:12])=[N:9][C:10]3[C:5]([CH:6]=2)=[CH:4][N:3]=[C:2]([NH:81][C:78](=[O:80])[CH3:79])[CH:11]=3)[CH:14]=[CH:15][C:16]=1[F:29]

Participants

7

Reactant 4

HCID 178AcetamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89815496HCID 89815496, compound

Product 1

HCID 71735419HCID 71735419, compoundYield 49.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

Sprage a mixture of 1-(5-(7-chloro-2-methyl-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3,3-dimethylbutyl)urea (0.200 g, 0.482 mmol), XantPhos (0.028 g, 0.048 mmol), Cs2CO3 (0.314 g, 0.964 mmol) and acetamide (0.142 g, 2.410 mmol) in dioxane (5 mL) with Ar, add Pd2(dba)3 (0.022 g, 0.024 mmol), heat at 100° C. for 7 h, then cool to RT overnight. Remove the solids via filtration through diatomaceous earth, rinse well with THF, wash the filtrate with brine (2×), dry over MgSO4, concentrate to dryness and purify via silica gel chromatography (MeOH/DCM). Triturate with MTBE, collect the solid via filtration and dry to afford the title compound (105 mg, 49%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.74 (s, 1H), 9.15 (d, J=0.8 Hz, 1H), 8.49 (s, 1H), 8.41 (d, J=2.6 Hz, 1H), 8.26 (dd, J=7.9, 2.3 Hz, 1H), 8.20 (s, 1H), 7.30 (dd, J=11.4, 8.4 Hz, 1H), 7.03 (ddd, J=8.4, 4.7, 2.3 Hz, 1H), 6.57 (t, J=5.6 Hz, 1 H), 3.11-3.05 (m, 2H), 2.57 (s, 3H), 2.15 (s, 3H), 1.36-1.31 (m, 2H), 0.88 (s, 9H); MS (ESI) m/z: 438.3 (M+H+).

Workup

  1. temperaturecool to RT overnight
  2. customRemove the solids
  3. filtrationvia filtration through diatomaceous earth
  4. washrinse well with THF
  5. washwash the filtrate with brine (2×)
  6. dry with materialdry over MgSO4
  7. concentrationconcentrate to dryness
  8. custompurify via silica gel chromatography (MeOH/DCM)
  9. customTriturate with MTBE
  10. customcollect the solid
  11. filtrationvia filtration
  12. customdry

Sources & evidence

ORD record
ord-6748a11208e94d9baf1e0a40a5e2587a
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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