1-Hydroxybenzotriazole → 5-{2-[5-(3,4-dichlorophenyl)furan-2-yl]ethylcarbamoyl}-1H-pyrazole-3-carboxylic acid

HRID 872431노트

반응식

HRID 872431 반응식
O.[NH:2]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][C:4]([C:10]([OH:12])=O)=[N:3]1.Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.Cl.[Cl:36][C:37]1[CH:38]=[C:39]([C:44]2[O:48][C:47]([CH2:49][CH2:50][NH2:51])=[CH:46][CH:45]=2)[CH:40]=[CH:41][C:42]=1[Cl:43]>CN(C=O)C.C(Cl)Cl.CCN(C(C)C)C(C)C.O>[Cl:36][C:37]1[CH:38]=[C:39]([C:44]2[O:48][C:47]([CH2:49][CH2:50][NH:51][C:10]([C:4]3[NH:3][N:2]=[C:6]([C:7]([OH:9])=[O:8])[CH:5]=3)=[O:12])=[CH:46][CH:45]=2)[CH:40]=[CH:41][C:42]=1[Cl:43]

참가 물질

9

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27237231H-Pyrazole-3,5-dicarboxylic acid monohydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 671683442-(5-(3,4-Dichlorophenyl)furan-2-yl)ethanamine hydrochloride

생성물 1

HCID 1785244995-{2-[5-(3,4-dichlorophenyl)furan-2-yl]ethylcarbamoyl}-1H-pyrazole-3-carboxylic acid

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회HCID 81531Diisopropylethylamine용매3회

실험 절차

3,5-Pyrazoledicarboxylic acid monohydrate (8.02 g, 46.1 mmol) was dissolved in the mixture of dry DMF (35 ml), dry DCM (35 ml) and DIPEA (7.9 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 3.37 g, 17.6 mmol), HOBt (2.28 g, 16.9 mmol), and DIPEA (3 ml, 2.23 g, 17.3 mmol) were added at RT. The solution was mixed for 10 min. Then, 2-[5-(3,4-dichlorophenyl)-furan-2-yl]ethylamine hydrochloride (3.46 g, 11.8 mmol) dissolved in the mixture of dry DCM (35 ml) and DIPEA (2.0 ml, 1.48 g, 11.5 mmol) was dropped to the solution at RT. After stirring overnight water was added. The product was extracted into ethyl acetate. The organic phase was washed with water, dried and evaporated. The crude product was purified by flash chromatography using DCM as an eluent. The product was triturated in hot methanol. 1H NMR (400 MHz, DMSO-d6): 2.95 (2H, t), 3.56 (2H, m), 6.33 (1H, d), 7.01 (1H, d), about 7.03 (1H, broad s), 7.61 (1H, distorted dd), 7.63 (1H, distorted d), 7.83 (1H, d), about 8.45 (1H, broad s), about 14.05 (1H, broad s).

후처리

  1. additionThe solution was mixed for 10 min
  2. additionwas dropped to the solution at RT
  3. additionwas added
  4. extractionThe product was extracted into ethyl acetate
  5. washThe organic phase was washed with water
  6. customdried
  7. customevaporated
  8. customThe crude product was purified by flash chromatography
  9. customThe product was triturated in hot methanol

출처 및 근거

ORD 기록
ord-98bca7bdf9f644b2a38386d818e5271b
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975254B2

반응 노트

불러오는 중…