Sodium Hydroxide → (2S,4R)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[3-chloro-6'-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-[2,4']bipyridinyl-3'-yl]-N-methyl-isobutyramide

HRID 1951697ノート

反応式

HRID 1951697 の反応式
[Cl:1][C:2]1[C:3](I)=[N:4][CH:5]=[CH:6][CH:7]=1.C([Mg]Cl)(C)C.[F:14][C:15]([F:49])([F:48])[C:16]1[CH:17]=[C:18]([C:26]([CH3:47])([CH3:46])[C:27]([N:29]([C:31]2[CH:32]=[N:33][C:34]([N:38]3[CH2:42][C@H:41]([OH:43])[CH2:40][C@H:39]3[CH2:44][OH:45])=[CH:35][C:36]=2I)[CH3:30])=[O:28])[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.[OH-].[Na+]>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:22]([F:23])([F:24])[C:20]1[CH:19]=[C:18]([C:26]([CH3:46])([CH3:47])[C:27]([N:29]([C:31]2[CH:32]=[N:33][C:34]([N:38]3[CH2:42][C@H:41]([OH:43])[CH2:40][C@H:39]3[CH2:44][OH:45])=[CH:35][C:36]=2[C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH3:30])=[O:28])[CH:17]=[C:16]([C:15]([F:49])([F:14])[F:48])[CH:21]=1

参加物

8

反応物 4

HCID 14798Sodium HydroxideHCID 108476073-Chloro-2-iodopyridineHCID 86597685HCID 86597685、化合物HCID 178418918HCID 178418918、化合物

生成物 1

HCID 86597691(2S,4R)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[3-chloro-6'-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-[2,4']bipyridinyl-3'-yl]-N-methyl-isobutyramide収率 40%

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒4 回

実験手順

To a solution of 0.500 g (2.09 mmol) 3-chloro-2-iodo-pyridine in 6 ml tetrahydrofuran 1.04 ml (2.09 mmol) of a 2 M solution of isopropylmagnesium chloride in tetrahydrofuran was added dropwise at −40° C. under an atmosphere of argon. After 30 min. 2.3 ml (4.2 mmol) of an anhydrous 1.8 M solution of zinc chloride in tetrahydrofuran was added slowly. The cooling bath was removed after completed addition, and the reaction mixture was stirred at room temperature for 90 min. A portion of 1.6 ml of this solution was added to a solution of 0.15 g (0.24 mmol) (2S,4R)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-iodo-pyridin-3-yl]-N-methyl-isobutyramide and 14 mg (0.012 mmol) tetrakis(triphenylphosphine)palladium(0) in 1 ml tetrahydrofuran. The mixture was heated at 100° C. under microwave irradiation for 30 min. After cooling to room temperature a 0.5 M solution of sodium hydroxide was added, and the mixture was extracted with three portions of dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 58 mg (40%) of the title compound as a light yellow solid.

後処理

  1. customThe cooling bath was removed
  2. additionaddition
  3. temperatureThe mixture was heated at 100° C. under microwave irradiation for 30 min
  4. additionwas added
  5. extractionthe mixture was extracted with three portions of dichloromethane
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-c7b2d7544bc4414b9e447f619acb3768
出典データセット
uspto-grants-2013_03
特許番号
US08404708B2

反応ノート

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