1-Hydroxybenzotriazole → 4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethylcyclohexyl]-3-[5-(4-methylphenyl)thiophen-2-yl]acrylamide

HRID 1169421노트

반응식

HRID 1169421 반응식
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.O[N:19]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.Cl.[CH3:42][N:43]([CH2:50][C@H:51]1[CH2:56][CH2:55][C@H:54](N)[CH2:53][CH2:52]1)[CH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.C1CCN2C(=NCCC2)CC1>C(#N)C.C(N(CC)CC)C>[CH3:42][N:43]([CH2:50][C:51]1([C:9]2[CH:10]=[C:11]([CH:13]=[CH:14][C:15]([NH2:19])=[O:17])[S:12][C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)[CH2:52][CH2:53][CH2:54][CH2:55][CH2:56]1)[CH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11345563(E)-3-[5-(4-methylphenyl)-thiophen-2-yl]acrylic acidHCID 178484107HCID 178484107, 화합물

생성물 1

HCID 867591874-(N-methyl-N-(tetrahydropyran-4-yl)aminomethylcyclohexyl]-3-[5-(4-methylphenyl)thiophen-2-yl]acrylamide수율 66.4%

시약·촉매·용매 2

HCID 6342Acetonitrile용매2회HCID 8471Triethylamine용매

실험 절차

Into a suspension of (E)-3-[5-(4-methylphenyl)-thiophen-2-yl]acrylic acid (200 mg) and 1-hydroxybenzotriazole (166 mg) in acetonitrile (10 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (235 mg), and the resulting mixture was stirred for 2 hours. Into the reaction mixture was added a solution of trans-4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexylamine dihydrochloride (368 mg), triethylamine (0.23 ml) and 1,8-diazabicyclo[5,4,0]-7-undecene (374 mg) in acetonitrile (10 ml), and the resulting mixture was stirred further for 18 hours. After the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with magnesium sulfate. After the resulting organic layer was concentrated under reduced pressure to remove the solvent, the residue was subjected to purification using column chromatography (ethanol/ethyl acetate 1:1) and to recrystallization (ethanol/ethyl acetate) to obtain trans-(E)-N-[4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethylcyclohexyl]-3-[5-(4-methylphenyl)thiophen-2-yl]acrylamide (compound 71) (246 mg) as yellow crystals.

후처리

  1. stirringthe resulting mixture was stirred further for 18 hours
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure, water
  3. additionwas added to the residue
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  6. dry with materialwas dried with magnesium sulfate
  7. concentrationAfter the resulting organic layer was concentrated under reduced pressure
  8. customto remove the solvent
  9. customthe residue was subjected to purification
  10. customto recrystallization (ethanol/ethyl acetate)

출처 및 근거

ORD 기록
ord-fcab948e4aea4fd2b70f9f489f63760d
출처 데이터셋
uspto-grants-2003_09
특허 번호
US06627651B1

반응 노트

불러오는 중…