Cesium carbonate → 3-({4-[(Dimethylamino)carbonyl]phenyl} amino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid

HRID 2364256노트

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HRID 2364256 반응식
[NH2:1][C:2]1[C:3]([C:16]([O:18]CC)=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].N[C:28]1[CH:38]=[CH:37][C:31]([C:32]([N:34]([CH3:36])[CH3:35])=[O:33])=[CH:30][CH:29]=1.CC(C)([O-])C.[Na+]>O1CCOCC1.ClCCl.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].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>[CH3:35][N:34]([CH3:36])[C:32]([C:31]1[CH:37]=[CH:38][C:28]([NH:1][C:2]2[C:3]([C:16]([OH:18])=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]3[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=3)[CH:7]=2)=[CH:29][CH:30]=1)=[O:33]

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 2355274-Amino-N,N-dimethylbenzamideHCID 23676156Sodium t-butoxideHCID 42637772Ethyl 3-amino-5-(4-fluorobenzyl)picolinate

생성물 1

HCID 694827073-({4-[(Dimethylamino)carbonyl]phenyl} amino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid수율 94%

시약·촉매·용매 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매2회

실험 절차

To a dry 100 mL flask under a nitrogen atmosphere was added ethyl 3-amino-5-(4-fluorobenzyl)pyridine-2-carboxylate (89 mg, 0.325 mmol) described in example 1, Cs2CO3 (148 mg, 0.455 mmol), Pd2dba3 (1.5 mg, 0.0016 mmol), and Xantphos (2.8 mg, 0.0049 mmol). Dioxane (15 mL) and 4-amino-N,N-dimethylbenzamide (1.25 mL of a 0.78 M solution in dioxane, 0.975 mmol) were added and the resulting solution was refluxed for 2 hrs. Sodium tert-butoxide (94 mg, 0.975 mmol) was added and the mixture was stirred for 10 minutes. The mixture was cooled to ambient temperature, diluted with dichloromethane, filtered through Celite and concentrated under reduced pressure. Water was added and the aqueous layer was washed with ethyl acetate and then acidified with 1 N hydrochloric acid to a pH of 4. The resulting yellow precipitate was collected by vacuum filtration to yield 3-({4-[(dimethylamino)carbonyl]phenyl}amino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid (120 mg, 94% yield). 1H NMR (CDCl3) δ 7.82 (s, 1 H), 7.46 (s, 1 H), 7.38 (d, J=8.4 Hz, 2 H), 7.13 (d, J=8.4 Hz, 2 H), 7.09-7.05 (m, 2 H), 6.97-6.93 (m, 2 H), 3.88 (s, 2 H), 3.07 (s, 3 H), 2.99 (s, 3 H); MS m/z 392 (M−1).

후처리

  1. temperaturethe resulting solution was refluxed for 2 hrs
  2. filtrationfiltered through Celite
  3. concentrationconcentrated under reduced pressure
  4. additionWater was added
  5. washthe aqueous layer was washed with ethyl acetate
  6. filtrationThe resulting yellow precipitate was collected by vacuum filtration

출처 및 근거

ORD 기록
ord-cc4b942df1fb4af5b607bcee6dec5803
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691991B2

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