Potassium Fluoride → Methyl 6-amino-2-(4-(difluoromethoxy)phenyl)-5-methoxypyrimidine-4-carboxylate

HRID 516559

反応式

HRID 516559 の反応式
[F-].[K+].[F:3][CH:4]([F:21])[O:5][C:6]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][CH:7]=1.[NH2:22][C:23]1[N:28]=[C:27](Cl)[N:26]=[C:25]([C:30]([O:32][CH3:33])=[O:31])[C:24]=1[O:34][CH3:35].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1>CCOC(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:22][C:23]1[N:28]=[C:27]([C:9]2[CH:8]=[CH:7][C:6]([O:5][CH:4]([F:3])[F:21])=[CH:11][CH:10]=2)[N:26]=[C:25]([C:30]([O:32][CH3:33])=[O:31])[C:24]=1[O:34][CH3:35]

参加物

9

反応物 4

HCID 522689Potassium FluorideHCID 3675707Tris(3-sulfonatophenyl) phosphineHCID 220323032-(4-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 52270701Methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate

生成物 1

HCID 90410744Methyl 6-amino-2-(4-(difluoromethoxy)phenyl)-5-methoxypyrimidine-4-carboxylate収率 39.8%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a 5-mL microwave safe vial was added potassium fluoride (0.151 g, 2.59 mmol), palladium (II) acetate (0.012 g, 0.052 mmol), 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.28 g, 1.037 mmol), methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate (0.226 g, 1.037 mmol), and 3,3′,3″-phosphinetriyltribenzenesulfonate (0.052 g, 0.104 mmol). A mixture of water (1 mL) and acetonitrile (2 mL) was added and the reaction was capped and placed in a Biotage Initiator™ microwave reactor for 6 min at 160° C., with external IR-sensor temperature monitoring from the side of the vessel. Upon cooling to room temperature, the reaction mixture was diluted with EtOAc (50 mL) and water (50 mL). An additional extraction using CH2Cl2 (50 mL) was combined with the EtOAc and dried over of Na2SO4 (50 g) after the CH2Cl2 layer was filtered through cotton plug. The combined organics were concentrated on a rotary evaporator and the residue was purified using a Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc to yield the title compound as a tan solid (134.4 mg).

後処理

  1. additionwas added
  2. customthe reaction was capped
  3. extractionAn additional extraction
  4. dry with materialdried over of Na2SO4 (50 g) after the CH2Cl2 layer
  5. filtrationwas filtered through cotton plug
  6. concentrationThe combined organics were concentrated on a rotary evaporator
  7. customthe residue was purified
  8. customa Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc

出典と根拠

ORDレコード
ord-4f6a3727b08b49e08055c2f63ee5073e
出典データセット
uspto-grants-2015_08
特許番号
US09113629B2

関連ノート

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