Sodium Carbonate → 3-Amino-6-(4-fluoro-phenyl)-5-trifluoromethyl-pyridine-2-carboxylic acid (2-hydroxy-2-methyl-propyl)-amide

HRID 444905

反応式

HRID 444905 の反応式
[OH:1][C:2]([CH3:20])([CH3:19])[CH2:3][NH:4][C:5]([C:7]1[C:12]([NH2:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[C:9](Br)[N:8]=1)=[O:6].[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+].CSC1NC(=S)NC(=S)N=1>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.CCO.C1(C)C=CC=CC=1>[OH:1][C:2]([CH3:20])([CH3:19])[CH2:3][NH:4][C:5]([C:7]1[C:12]([NH2:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[C:9]([C:25]2[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=2)[N:8]=1)=[O:6]

参加物

10

反応物 4

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 12210973Si-TMTHCID 584423673-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (2-hydroxy-2-methyl-propyl)-amide

生成物 1

HCID 584423153-Amino-6-(4-fluoro-phenyl)-5-trifluoromethyl-pyridine-2-carboxylic acid (2-hydroxy-2-methyl-propyl)-amide

試薬・触媒・溶媒 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred suspension of 3-amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (2-hydroxy-2-methyl-propyl)-amide (Ex. 1.10) (180 mg, 0.505 mmol) and 4-fluorophenylboronic acid (106 mg, 0.758 mmol) in a 2:1 mixture of toluene:EtOH (12 ml) under nitrogen was added 2M Na2CO3(aq) (1.011 ml, 2.022 mmol) followed by Pd(dppf)Cl2.CH2Cl2 adduct (41 mg, 0.051 mmol). The reaction mixture was heated using microwave radiation at 140° C. for 1 hour and then allowed to cool to RT. The mixture was diluted with EtOAc (100 ml) and washed with water (100 ml). The organic phase was separated, filtered through Celite® (filter material) dried (MgSO4) and concentrated in vacuo to yield a brown oil/solid. Purification by chromatography on silica eluting with MeOH/DCM yielded a yellow oil/solid. This was passed through a 500 mg Isolute® Si-TMT cartridge (2,4,6-trimercaptotriazine silica, pre-wetted with DCM) eluting with 30% MeOH/DCM (50 ml) to afford a yellow oil/solid. The crude product was dried in vacuo and slurried in ˜0.5 ml DCM. The resulting suspension was removed by filtration and the filtrate was evaporated to yield the title compound as a light yellow/brown foam-like solid; LC-MS Rt=5.30 mins [M+H]+ 372 (Method 10 minLC_v002).

後処理

  1. temperatureThe reaction mixture was heated
  2. customat 140° C.
  3. customfor 1 hour
  4. washwashed with water (100 ml)
  5. customThe organic phase was separated
  6. filtrationfiltered through Celite® (filter material)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto yield a brown oil/solid
  10. customPurification by chromatography on silica eluting with MeOH/DCM
  11. customyielded a yellow oil/solid
  12. washeluting with 30% MeOH/DCM (50 ml)
  13. customto afford a yellow oil/solid
  14. dry with materialThe crude product was dried in vacuo
  15. customThe resulting suspension was removed by filtration
  16. customthe filtrate was evaporated

出典と根拠

ORDレコード
ord-560688d4c67f47ba8099443bfd4a5fce
出典データセット
uspto-grants-2013_07
特許番号
US08476269B2

関連ノート

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