Hydrochloric Acid → HCID 178456364, 화합물

HRID 526572

반응식

HRID 526572 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2].Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1.Br.Br.[CH2:49]([N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)[CH2:50][CH3:51].CCN(C(C)C)C(C)C.Cl>CN(C=O)C.O>[OH:14][C:13]1[N:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([N:55]3[CH2:56][CH2:57][N:52]([CH2:49][CH2:50][CH3:51])[CH2:53][CH2:54]3)=[O:20])=[CH:17][N:16]=2)[N:11]=[CH:10][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=1[CH3:24]

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3085288N-Propylpiperazinium dibromideHCID 178426451HCID 178426451, 화합물

생성물 1

HCID 178456364HCID 178456364, 화합물

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (0.5 g, 1.561 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.449 g, 2.342 mmol), HOBT (0.359 g, 2.342 mmol) and 1-propylpiperazine dihydrobromide (0.543 g, 1.873 mmol) in DMF (1.56 mL) and added DIPEA (1.09 mL, 6.24 mmol) to give an orange solution. After stirring for 20 minutes the reaction mixture was heated to 60° C. for 3 hours, then was diluted with water (5 mL) and acidified with 6N aqueous hydrochloric acid to pH 6 and stirred at ambient temperature for 30 minutes to give a solid. The solid was collected by filtration, washed with water (3 mL) and suspended in ACN (10 mL). The suspension was treated with 1N aqueous hydrochloric acid (2 mL) and heated to 40° C. Ethyl ether was then added until the mixture became slightly cloudy (˜8 mL) and then allowed to cool to ambient temperature to give a solid, and then cooled in an ice bath for 30 minutes. The solid was collected by filtration and dried in vacuum at 80° C. for 1.5 hour to give the title compound as a hydrochloride salt (81.3 mg, 0.174 mmol, 11.15%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92 (t, J=7.45 Hz, 3H) 1.64-1.79 (m, 2H) 2.43 (s, 3H) 2.81-3.20 (m, 4H) 3.21-4.90 (m, 6H) 7.67 (d, J=7.58 Hz, 1H) 7.71-7.91 (m, 2H) 7.93-8.74 (m, 4H) 10.75 (br. s., 1H) 13.23 (br. s., 1H); [M+H]+ 431.

후처리

  1. customto give an orange solution
  2. stirringstirred at ambient temperature for 30 minutes
  3. customto give a solid
  4. filtrationThe solid was collected by filtration
  5. washwashed with water (3 mL)
  6. additionThe suspension was treated with 1N aqueous hydrochloric acid (2 mL)
  7. temperatureheated to 40° C
  8. additionEthyl ether was then added until the mixture
  9. temperatureto cool to ambient temperature
  10. customto give a solid
  11. temperaturecooled in an ice bath for 30 minutes
  12. filtrationThe solid was collected by filtration
  13. customdried in vacuum at 80° C. for 1.5 hour

출처 및 근거

ORD 기록
ord-c2ce3fa13a9f4982bf47436899b61458
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345713B2

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