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

HRID 925273노트

반응식

HRID 925273 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e5c3b8a414b34f2a92ab8b9a865cf42d
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284286B2

반응 노트

불러오는 중…