Cesium carbonate → 7-(2,4-dichlorophenyl)-N-[2-methoxy-1-(methoxymethyl)ethyl]-2,6-dimethylpyrrolo[1,2-b]pyridazin-4-amine

HRID 1791155노트

반응식

HRID 1791155 반응식
Br[C:2]1[C:3]2[N:4]([C:9]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])=[C:10]([CH3:12])[CH:11]=2)[N:5]=[C:6]([CH3:8])[CH:7]=1.[CH3:21][O:22][CH2:23][CH:24]([NH2:28])[CH2:25][O:26][CH3:27].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[C:9]1[N:4]2[N:5]=[C:6]([CH3:8])[CH:7]=[C:2]([NH:28][CH:24]([CH2:25][O:26][CH3:27])[CH2:23][O:22][CH3:21])[C:3]2=[CH:11][C:10]=1[CH3:12]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 15141601,3-Dimethoxypropan-2-amine2회HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl2회HCID 220281714-Bromo-7-(2,4-dichlorophenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazine

생성물 1

HCID 104541157-(2,4-dichlorophenyl)-N-[2-methoxy-1-(methoxymethyl)ethyl]-2,6-dimethylpyrrolo[1,2-b]pyridazin-4-amine

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매2회HCID 80711,2-Dimethoxyethane용매

실험 절차

A mixture of 4-bromo-7-(2,4-dichlorophenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazine (0.143 g, 0.387 mmol), 1,3-dimethoxypropan-2-amine (0.092 g, 0.774 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-1,1′-biphenyl-2-amine (0.011 g, 0.029 mmol), Cs2CO3 (0.176 g, 0.542 mmol) and Pd2(dba)3 (0.018 g, 0.02 mmol) in DME (5.0 mL) is refluxed for 24 h. After cooling to room temperature, to the mixture is added 1,3-dimethoxypropan-2-amine (0.092 g, 0.774 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-1,1′-biphenyl-2-amine (0.011 g, 0.029 mmol) and Pd2(dba)3 (0.018 g, 0.02 mmol). The mixture is refluxed for another 24 h. After cooling to room temperature, the mixture is filtered and washed with EtOAc. The filtrate is concentrated in vacuo to dryness, the residue is subjected to preparative TLC (silica gel, 1/5 EtOAc/heptane) to give 0.07 g (44%) of light yellow solid as the title compound: mp 154–155° C. (CH2Cl2/heptane); 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J=2.0 Hz, 1H), 7.41 (d, J=8.3 Hz, 1H), 7.36 (d, J=8.3, 2.0 Hz, 1H), 6.35 (s, 1H), 5.65 (s, 1H), 4.88 (d, J=8.4 Hz, 1H), 3.91–3.82 (m, 1H), 3.69–3.66 (m, 2H), 3.61–3.55 (m, 2H), 3.45 (s, 3H), 3.44 (s, 3H), 2.33 (s, 3H), 2.21 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 150.4, 142.4, 136.4, 134.3, 134.1, 129.6, 129.3, 126.8, 123.3, 120.6, 119.3, 95.1, 88.0, 70.9, 59.3, 51.3, 22.4, 12.3; IR (diffuse reflectance) 3336, 2924, 1560, 1490, 1372, 1330, 1192, 1113, 1098, 1078, 1051, 961, 821, 811, 778 cm−1; MS (EI) m/z 407 (M+), 409 (M+); HRMS (FAB) calcd for C20H23Cl2N3O2+H 408.1245, found 408.1244; Anal. Calcd for C20H23Cl2N3O2: C, 58.83; H, 5.68; N, 10.29. Found: C, 58.90; H, 5.78; N, 10.13.

후처리

  1. temperatureis refluxed for 24 h
  2. temperatureThe mixture is refluxed for another 24 h
  3. temperatureAfter cooling to room temperature
  4. filtrationthe mixture is filtered
  5. washwashed with EtOAc
  6. concentrationThe filtrate is concentrated in vacuo to dryness

출처 및 근거

ORD 기록
ord-612c05ec5c2e41d1a9c71169bc97def9
출처 데이터셋
uspto-grants-2006_07
특허 번호
US07074791B2

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