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

HRID 2364256ノート

反応式

HRID 2364256 の反応式
[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]

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-cc4b942df1fb4af5b607bcee6dec5803
出典データセット
uspto-grants-2014_04
特許番号
US08691991B2

反応ノート

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