Water → HCID 86703990、化合物

HRID 1773911ノート

反応式

HRID 1773911 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([O-])([O-])=O.[K+].[K+].[OH:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([NH:38][C:39]([C:41]2[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][CH:42]=2)=[O:40])[CH2:34][CH2:33]1.O>C1COCC1.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]>[OH:31][CH:32]1[CH2:33][CH2:34][CH:35]([NH:38][C:39](=[O:40])[C:41]2[CH:46]=[CH:45][C:44]([C:2]3[N:11]=[C:10]4[N:4]([CH2:5][CH2:6][C:7]5[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=5[CH:9]4[O:12][CH:13]4[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]4)[C:3]=3[CH3:24])=[CH:43][CH:42]=2)[CH2:36][CH2:37]1

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 86703973HCID 86703973、化合物HCID 178523805HCID 178523805、化合物

生成物 1

HCID 86703990HCID 86703990、化合物

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
95 °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) (50 mg, 0.114 mmoles) in THF (0.7 mL) in a screw-capped vial under argon are added a 1M aqueous solution of K2CO3 (0.5 mL, 0.5 mmole), PdCl2(dppf)2 (4.5 mg, 6 μmole) and 4-(trans-4-hydroxycyclohexylcarbamoyl)phenylboronic acid (45 mg, 0.150 mmole). The reaction mixture is heated at 95° C. overnight. Water is added to the reaction mixture and the aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) with a gradient from (98:2:0.2) to (96.5:3.5:0.35). The residue is purified by preparative TLC over silica gel using (CH2Cl2:MeOH:NH4OH) with a gradient from (9:1:1) to afford N-(4-hydroxycyclohexyl)-4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]benzamide.

後処理

  1. extractionthe aqueous phase is extracted three times with CH2Cl2
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is pre-purified by silica gel chromatography
  6. customThe residue is purified by preparative TLC over silica gel using (CH2Cl2:MeOH:NH4OH) with a gradient from (9:1:1)

出典と根拠

ORDレコード
ord-850bf987aa6e4d31844cc2da1c5b9527
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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