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

HRID 1791155ノート

反応式

HRID 1791155 の反応式
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]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 15141601,3-Dimethoxypropan-2-amine2 回HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl2 回HCID 220281714-Bromo-7-(2,4-dichlorophenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazine

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 80711,2-Dimethoxyethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-612c05ec5c2e41d1a9c71169bc97def9
出典データセット
uspto-grants-2006_07
特許番号
US07074791B2

反応ノート

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