Triethylamine → N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide

HRID 77693노트

반응식

HRID 77693 반응식
[F:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[C:9](Cl)=[O:10].[C:12]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][NH:21][CH:22]2[CH2:24][CH2:23]2)=[CH:14][CH:13]=1.C(N(CC)CC)C.CCCCCCC.C(OCC)(=O)C>O1CCCC1>[C:12]1([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]([CH:22]2[CH2:24][CH2:23]2)[C:9]([C:3]2[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=2[F:1])=[O:10])=[CH:14][CH:13]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 108668795-Fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chlorideHCID 21899848Ethylacetate heptaneHCID 43591686N-[2-(biphenyl-4-yloxy)ethyl]cyclopropanamine

생성물 1

HCID 67071809N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide수율 47.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
80 °C

실험 절차

At ambient temperature, a solution of 230 mg (1.29 mmol) of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride in 1 ml of tetrahydrofurane is added dropwise to a mixture of 300 mg (1.18 mmol) of N-[2-(biphenyl-4-yloxy)ethyl]cyclopropanamine as its hydrochloride salt and 250 mg (2.48 mmol) of triethylamine in 5 ml of tetrahydrofurane. The reaction mixture is stirred for 2 hrs at 80° C. The solvent is removed under vacuum and 10 ml of water are then added to the residue. The watery layer is extracted twice with ethyl acetate (2×25 ml) and the combined organic layers are successively washed by a 1 N solution of HCl, a saturated solution of potassium carbonate and brine and dried of magnesium sulfate to gave after concentration 750 mg of a yellow oil. Column chromatography (gradient heptane/ethyl acetate) yielded 220 mg (47% yield) of N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide as a colourless oil (M+H=394).

후처리

  1. customThe solvent is removed under vacuum and 10 ml of water
  2. additionare then added to the residue
  3. extractionThe watery layer is extracted twice with ethyl acetate (2×25 ml)
  4. washthe combined organic layers are successively washed by a 1 N solution of HCl
  5. dry with materiala saturated solution of potassium carbonate and brine and dried of magnesium sulfate
  6. customto gave after concentration 750 mg of a yellow oil

출처 및 근거

ORD 기록
ord-a75bfc9af4ef48eba05ebfdd706ba5e9
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841332B2

반응 노트

불러오는 중…