4-Methylmorpholine → 4-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-thiazole-5-carboxylic acid amide

HRID 925273ノート

反応式

HRID 925273 の反応式
[F:1][C:2]([F:21])([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:3][CH2:4][S:5][C:6]1[N:7]=[CH:8][S:9][C:10]=1[C:11]([OH:13])=O.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[F:51][C:52]1[CH:59]=[CH:58][C:55]([CH2:56][NH2:57])=[CH:54][CH:53]=1>CN(C=O)C>[F:21][C:2]([F:1])([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:3][CH2:4][S:5][C:6]1[N:7]=[CH:8][S:9][C:10]=1[C:11]([NH:57][CH2:56][C:55]1[CH:58]=[CH:59][C:52]([F:51])=[CH:53][CH:54]=1)=[O:13]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 673264-FluorobenzylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 867201704-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-thiazole-5-carboxylic acid

生成物 1

HCID 762877044-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-thiazole-5-carboxylic acid amide収率 47%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 4-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-thiazole-5-carboxylic acid (0.15 g, 0.45 mmol) in DMF (3 ml) are added O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (216 mg, 0.68 mmol) and N-methylmorpholine (0.01 ml, 0.9 mmol) at 0° C. followed by the addition of 4-fluorobenzyl amine (67 mg, 0.54 mmol). The reaction mixture is stirred at RT for 3 h. After completion of the reaction, the mixture is poured onto ice-water, extracted with EtOAc (3×50 ml). The combined organic layers are washed with brine (50 ml), dried over sodium sulfate and evaporated to dryness to yield the crude product, which is purified by column chromatography (silica gel, 15% acetone/hexane) affording 4-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-thiazole-5-carboxylic acid amide (example 14) (93 mg, 0.21 mmol, 47%). [M+H]+ 441.1.

後処理

  1. customAfter completion of the reaction
  2. additionthe mixture is poured onto ice-water
  3. extractionextracted with EtOAc (3×50 ml)
  4. washThe combined organic layers are washed with brine (50 ml)
  5. dry with materialdried over sodium sulfate
  6. customevaporated to dryness
  7. customto yield the crude product, which
  8. customis purified by column chromatography (silica gel, 15% acetone/hexane)

出典と根拠

ORDレコード
ord-e5c3b8a414b34f2a92ab8b9a865cf42d
出典データセット
uspto-grants-2016_03
特許番号
US09284286B2

反応ノート

読み込み中…