Sodium Carbonate → 5-(1-(6-(1,4-diazepan-1-yl)pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-2-methylpyridazin-3(2H)-one

HRID 57851

반응식

HRID 57851 반응식
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N:17]4[CH2:23][CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[N:12]=3)[C:4]=2[CH:3]=1.[CH3:24][N:25]1[C:30](=[O:31])[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[N:17]1([C:13]2[N:12]=[C:11]([N:10]3[C:4]4[CH:3]=[C:2]([C:28]5[CH:27]=[N:26][N:25]([CH3:24])[C:30](=[O:31])[CH:29]=5)[N:7]=[CH:6][C:5]=4[CH:8]=[N:9]3)[CH:16]=[CH:15][CH:14]=2)[CH2:23][CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 867070506-Chloro-1-[6-(1,4-diazepan-1-yl)-2-pyridyl]pyrazolo[4,3-c]pyridineHCID 867070512-Methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydropyridazin-3-one

생성물 1

HCID 727153805-(1-(6-(1,4-diazepan-1-yl)pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-2-methylpyridazin-3(2H)-one수율 8.5%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 6342Acetonitrile용매

반응 조건

온도
150 °C

실험 절차

A mixture of 6-chloro-1-[6-(1,4-diazepan-1-yl)-2-pyridyl]pyrazolo[4,3-c]pyridine (0.3190 mmol; 104.9 mg), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazin-3-one (0.4786 mmol; 113.0 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.03190 mmol; 26.6 mg), potassium acetate (0.4786 mmol; 0.48 mL) and sodium carbonate (0.4786 mmol; 0.48 mL) in Acetonitrile (10 mL) in a pressure tube was heated under microwave at 150° C. for 15 min. The mixture was filtered through Celite. The filtrated was concentrated. The residue was purified on silica eluted with 10% MeOH in DCM with 1% NH4OH. The product obtained (29 mg, purity>90%) was further purified by reverse phase HPLC to afford 148 as an off-white solid (10.9 mg, 8.5%). 1H NMR (400 MHz, DMSO) δ 9.39-9.31 (s, 1H), 9.08-9.01 (s, 1H), 8.72-8.65 (s, 1H), 8.56-8.51 (d, J=2.1 Hz, 1H), 8.31-8.22 (s, 1H), 7.76-7.69 (t, J=8.1 Hz, 1H), 7.42-7.38 (d, J=2.1 Hz, 1H), 7.22-7.18 (d, J=7.7 Hz, 1H), 6.69-6.62 (d, J=8.5 Hz, 1H), 3.87-3.79 (m, 4H), 3.74-3.72 (s, 3H), 3.05-3.00 (m, 2H), 2.83-2.77 (m, 2H), 1.94-1.87 (m, 2H); MS (ESI) m/z: 403.2 [M+H]+.

후처리

  1. filtrationThe mixture was filtered through Celite
  2. concentrationThe filtrated was concentrated
  3. customThe residue was purified on silica
  4. washeluted with 10% MeOH in DCM with 1% NH4OH
  5. customThe product obtained (29 mg, purity>90%)
  6. customwas further purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-66bb8d6d7a6642aba3ae5e0cbf8e7169
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434725B2

연결된 노트

불러오는 중…