Potassium Phosphate, Tribasic → (4S,6S)-4-(2-fluoro-5-(5-(prop-1-yn-1-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930321ノート

反応式

HRID 930321 の反応式
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[CH:11]=[CH:12][C:13]([F:29])=[C:14]([C@:16]2([CH2:27][F:28])[CH2:21][C@@H:20]([C:22]([F:25])([F:24])[F:23])[O:19][C:18]([NH2:26])=[N:17]2)[CH:15]=1.[C:30]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[N:37][CH:38]=1)#[C:31][CH3:32]>O1CCOCC1.O.O.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[F:29][C:13]1[CH:12]=[CH:11][C:10]([C:35]2[CH:36]=[N:37][CH:38]=[C:33]([C:30]#[C:31][CH3:32])[CH:34]=2)=[CH:15][C:14]=1[C@:16]1([CH2:27][F:28])[CH2:21][C@@H:20]([C:22]([F:25])([F:24])[F:23])[O:19][C:18]([NH2:26])=[N:17]1

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 574164825-(1-Propynyl)pyridine-3-boronic Acid (contains varying amounts of Anhydride)HCID 86732143(4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

生成物 1

HCID 86732150(4S,6S)-4-(2-fluoro-5-(5-(prop-1-yn-1-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine収率 55.5%

試薬・触媒・溶媒 3

HCID 178482226HCID 178482226、化合物触媒HCID 962Water溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

実験手順

A mixture of potassium phosphate (0.168 g, 0.792 mmol), (4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (8a, 0.0985 g, 0.264 mmol), (5-(prop-1-yn-1-yl)pyridin-3-yl)boronic acid (0.106 g, 0.660 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (9.35 mg, 0.013 mmol) in dioxane/water (2.0/0.5 mL) was irradiated at 110° C. for 30 min. The reaction mixture was diluted with water and extracted with DCM three times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography: 12 g, 0-100% EtOAc/DCM. The product was obtained as a white solid (0.060 g, 55% yield). MS m/z=410 [M+H]+. Calculated for C20H16F5N3O: 409.4.

後処理

  1. extractionextracted with DCM three times
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-7b36fbf8a17e4d67ad2845ae34bd2ef9
出典データセット
uspto-grants-2016_03
特許番号
US09296734B2

反応ノート

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