Lithium Chloride → HCID 86704016、化合物

HRID 1773927ノート

反応式

HRID 1773927 の反応式
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[CH3:24].C([Sn](CCCC)(CCCC)[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1)CCC.[K].[Li+].[Cl-]>CN(C=O)C.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>[CH3:24][C:3]1[N:4]2[C:10]([CH:9]([O:12][CH:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)[C:8]3[CH:20]=[CH:21][CH:22]=[CH:23][C:7]=3[CH2:6][CH2:5]2)=[N:11][C:2]=1[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1

参加物

6

反応物 3

HCID 433294Lithium ChlorideHCID 86703973HCID 86703973、化合物HCID 86704017HCID 86704017、化合物

生成物 1

HCID 86704016HCID 86704016、化合物

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

To a solution of 2-iodo-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 133) (110 mg, 0.251 mmole) in DMF (4 mL) are added potassium 4-tributylstannylpyridine (354 mg, 1 mmole), Pd(PPh3)4 (28 mg, 0.025 mmole), LiCl (50 mg, 1.25 mmole). The flask is evacuated and filled with argon. The reaction mixture is heated at 110° C. for 5 hours. AcOEt and water are added, as well as a 10% KF solution. The aqueous phase is extracted with AcOEt. The organic phase is washed with 0.5N HCl. The HCl phase is made alkaline with 1H NaOH and the aqueous phase is extracted with AcOEt. The organic phase is dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) (98:2) then (CH2Cl2:MeOH:NH4OH) (95:5:0.5). The residue is the re-purified to afford by silica gel chromatography eluting with (toluene:acetone:NEt3) (10:90:2) to (5:95:5) to give 1-methyl-4-(1-methylpiperidin-4-yloxy)-2-pyridin-4-yl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

後処理

  1. customThe flask is evacuated
  2. additionfilled with argon
  3. additionAcOEt and water are added
  4. extractionThe aqueous phase is extracted with AcOEt
  5. washThe organic phase is washed with 0.5N HCl
  6. extractionthe aqueous phase is extracted with AcOEt
  7. dry with materialThe organic phase is dried over MgSO4
  8. filtrationfiltered
  9. customthe solvent removed under reduced pressure
  10. customThe residue is purified by silica gel chromatography
  11. washeluting with (CH2Cl2:MeOH) (98:2)
  12. customre-purified
  13. customto afford by silica gel chromatography
  14. washeluting with (toluene:acetone:NEt3) (10:90:2) to (5:95:5)

出典と根拠

ORDレコード
ord-26684436bb62451199808b2dda9e6123
出典データセット
uspto-grants-2016_02
特許番号
US09255101B2

反応ノート

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