Ammonia → 3-methyl-3-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylsulfanyl}-butan-1-ol

HRID 1773899ノート

反応式

HRID 1773899 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]=[C:16]3[N:10]([CH2:11][CH2:12][C:13]4[CH:29]=[CH:28][CH:27]=[CH:26][C:14]=4[CH:15]3[O:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[C:9]=2[CH3:30])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[SH:40][C:41]([CH3:46])([CH3:45])[CH2:42][CH2:43][OH:44].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.N>O1CCOCC1.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].O>[CH3:45][C:41]([S:40][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]=[C:16]3[N:10]([CH2:11][CH2:12][C:13]4[CH:29]=[CH:28][CH:27]=[CH:26][C:14]=4[CH:15]3[O:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[C:9]=2[CH3:30])=[CH:4][CH:3]=1)([CH3:46])[CH2:42][CH2:43][OH:44]

参加物

9

反応物 5

HCID 222AmmoniaHCID 81531Diisopropylethylamine2 回HCID 5206823-Mercapto-3-methyl-1-butanol2 回HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2 回HCID 726953822-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

生成物 1

HCID 867039753-methyl-3-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylsulfanyl}-butan-1-ol

試薬・触媒・溶媒 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒2 回HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

To a solution of compound 2-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 122A) (60 mg, 0.129 mmoles) in 1,4-dioxane (1.5 mL) in a screw-capped vial under argon are added diisopropylethylamine (33 μL, 0.142 mmole), 3-mercapto-3-methylbutan-1-ol (20 μL, 0.193 mmole), bis(dibenzilideneacetone)palladium(0) (4 mg, 6.4 μmole), Xantphos (4 mg, 6.4 μmole). The reaction mixture is heated at 110° C. overnight. As the reaction is not complete, bis(dibenzilideneacetone)Palladium(0) (4 mg, 6.4 μmole), Xantphos (4 mg, 6.4 μmole), diisopropylethylamine (33 μL, 0.142 mmole), 3-mercapto-3-methylbutan-1-ol (20 μL, 0.193 mmole) are added to the reaction mixture. After one overnight at 120° C., water is added to the reaction mixture and pH adjusted to 9-10 by adding concentrated ammonia solution. 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 purified by silica gel chromatography using (CH2Cl2:MeOH) as eluent with a gradient from (95:5) to (90:10) to afford 3-methyl-3-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylsulfanyl}-butan-1-ol.

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 purified by silica gel chromatography

出典と根拠

ORDレコード
ord-65f0a248fe974ed5b77589409537192b
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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