Cesium carbonate → HCID 71584877, 화합물

HRID 1257281노트

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HRID 1257281 반응식
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:15]3[C:16]([CH3:34])=[CH:17][C:18]([F:33])=[C:19]([NH:21][C:22]([NH:24][C:25]4[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[CH:26]=4)=[O:23])[CH:20]=3)[C:8](=[O:14])[N:9]2[CH2:12][CH3:13])=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:41][N:42]([CH3:46])[C:43]([NH2:45])=[O:44].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].CN(C=O)C.CCOC(C)=O.O>[F:32][C:27]1[CH:26]=[C:25]([NH:24][C:22](=[O:23])[NH:21][C:19]2[C:18]([F:33])=[CH:17][C:16]([CH3:34])=[C:15]([C:7]3[C:8](=[O:14])[N:9]([CH2:12][CH3:13])[C:10]4[C:5]([CH:6]=3)=[CH:4][N:3]=[C:2]([NH:45][C:43](=[O:44])[N:42]([CH3:46])[CH3:41])[CH:11]=4)[CH:20]=2)[CH:30]=[C:29]([F:31])[CH:28]=1

참가 물질

10

반응물 4

HCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86713696HCID 86713696, 화합물

생성물 1

HCID 71584877HCID 71584877, 화합물수율 5.7%

시약·촉매·용매 5

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A mixture of 1-(5-(7-chloro-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3,5-difluorophenyl)urea (287 mg, 0.589 mmol), Cs2CO3 (576 mg, 1.768 mmol), N,N-dimethylurea (260 mg, 2.95 mmol) and Xantphos (102 mg, 0.177 mmol) in dioxane (5 mL) was sparged with Ar, treated with Pd2(dba)3 (81 mg, 0.088 mmol) and heated at 100° C. overnight. The mixture was cooled to RT, treated with water, EtOAc and DMF and the solids removed via filtration through diatomaceous earth. The layers of the filtrate were separated, the organic layer washed with brine, dried over Na2SO4, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure, the aqueous residue treated with satd. NaHCO3 and stirred overnight. The resulting solid was collected via filtration and dried to afford 3-(3-(5-(3-(3,5-difluorophenyl)ureido)-4-fluoro-2-methylphenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)-1,1-dimethylurea (18 mg, 5% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.41 (s, 1H), 9.17 (s, 1H), 8.65 (m, 2H), 8.01 (s, 1H), 7.90 (d, J=8.3 Hz, 1H), 7.86 (s, 1H), 7.20-7.11 (m, 3H), 6.78 (m, 1H), 4.18 (q, J=7.1 Hz, 2H), 2.97 (s, 6H), 2.08 (s, 3H), 1.24 (t, J=7.1 Hz, 3H); MS (ESI) m/z: 539.2 [M+H]+.

후처리

  1. customwas sparged with Ar
  2. temperatureThe mixture was cooled to RT
  3. customthe solids removed via filtration through diatomaceous earth
  4. customThe layers of the filtrate were separated
  5. washthe organic layer washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  9. customThe organics were removed under reduced pressure
  10. additionthe aqueous residue treated with satd
  11. filtrationThe resulting solid was collected via filtration
  12. customdried

출처 및 근거

ORD 기록
ord-da0c2219fdc042a5aca63c4903c6bcad
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461179B1

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