Dimethylformamide → [7-(2-Methoxy-phenyl)-5-vinyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

HRID 1261901ノート

反応式

HRID 1261901 の反応式
Br[C:2]1[CH:3]=[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])[N:5]2[C:10]=1[CH:9]=[N:8][C:7]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:14][CH:13]=1)=[N:6]2.[CH:33](B(O)O)=[CH2:34].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:32][O:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C:4]1[N:5]2[C:10]([CH:9]=[N:8][C:7]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:6]2)=[C:2]([CH:33]=[CH2:34])[CH:3]=1

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 4683185Vinylboronic acidHCID 66711068[5-Bromo-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

生成物 1

HCID 66711513[7-(2-Methoxy-phenyl)-5-vinyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

試薬・触媒・溶媒 1

HCID 178418397HCID 178418397、化合物触媒

反応条件

温度
140 °C

実験手順

Into a 30 mL vial [5-Bromo-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (90.0 mg, 0.000182 mol), Vinyl boronic acid (100 mg, 0.002 mol), Potassium carbonate (1.12 g, 0.00814 mol), and Tetrakis(triphenylphosphine)palladium (0) (21.3 mg, 0.0000184 mol) were added and purged under an atmosphere of Nitrogen for 10 minutes. N,N-Dimethylformamide (5 mL, 0.06 mol) was added. The reaction mixture was heated at 140° C. for 4 hours. The reaction was partitioned with water and EtOAc. The organic was separated and washed with water. Subsequently the organic was washed with Brine, and dried over magnesium sulfate. The solid was filtered and washed with EtOAc. The solvent was removed under vacuum. The product was isolated via ISCO column chromatography with DCM and Methanol as eluant (0 to 10% methanol). The collected fractions afforded [7-(2-Methoxy-phenyl)-5-vinyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine a yellow solid (68 mg, 85%). MP 150-151° C. LCMS (E/I+) 441.24 (M+H). NMR 1H (DSMO-d6)-9.17 (s, 1H), 9.14 (s, 1H), 7.75 (dd, 1H, JJ=1.60, 6.04 Hz), 7.53 (d, 2H, J=8.96 Hz), 7.48 (dt, 1H, JJ=1.52, 6.92 Hz), 7.22 (d, 1H, J=8.36 Hz), 7.00-7.18 (m, 3H), 6.78 (d, 2H, J=9.04 Hz), 5.78 (d, 1H, J=17.56 Hz), 5.24 (d, 1H, J=11.81 Hz), 3.80 (s, 3H), 3.02 (t, 4H, J=4.56 Hz), 2.44 (t, 4H, J=4.68 Hz), 2.21 (s, 3H).

後処理

  1. custompurged under an atmosphere of Nitrogen for 10 minutes
  2. customThe reaction was partitioned with water and EtOAc
  3. customThe organic was separated
  4. washwashed with water
  5. washSubsequently the organic was washed with Brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationThe solid was filtered
  8. washwashed with EtOAc
  9. customThe solvent was removed under vacuum
  10. customThe product was isolated via ISCO column chromatography with DCM and Methanol as eluant (0 to 10% methanol)

出典と根拠

ORDレコード
ord-bd2a59ccecad4ee08808c68658297e2c
出典データセット
uspto-grants-2013_06
特許番号
US08471005B2

反応ノート

読み込み中…