Dimethyl Sulfoxide → (S)-6,7-Difluoro-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131451

反応式

HRID 131451 の反応式
Cl.[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([NH2:16])[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1.[CH3:20][O:21][CH2:22][CH2:23][CH:24]1[CH2:29]N[CH2:27][CH2:26][NH:25]1.CS(C)=O>C1(C)C=CC=CC=1>[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([N:16]3[CH2:27][CH2:26][NH:25][C@@H:24]([CH2:23][CH2:22][O:21][CH3:20])[CH2:29]3)[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1

参加物

5

反応物 3

HCID 679Dimethyl SulfoxideHCID 178066642-(2-Methoxyethyl)piperazineHCID 1363885776,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride

生成物 1

HCID 135434034(S)-6,7-Difluoro-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene収率 66.4%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
115 °C

実験手順

Add 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (65.0 g, 215 mmol) and 2-(2-methoxy-ethyl)-piperazine (96.3 g, 668 mmol) to a solution of DMSO (650 mL) and toluene (1300 mL) with stirring under nitrogen. Heat at gentle reflux (115° C.) for 2 days, and then allow cooling to ambient temperature. Remove most of the organic portion under reduced pressure, and then partition the residue between ethyl acetate (450 mL) and aqueous saturated ammonium chloride solution (450 mL). Separate the layers, and then extract the aqueous layer with ethyl acetate (3×200 mL). Extract the combined organic layers with brine (3×200 mL). Concentrate the organic layer under reduced pressure. Purify the crude product by flash chromatography, eluting with 90:10/methylene chloride:MeOH to give 56 g (66%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 7.70 (s, 1H), 6.74 (m, 2H), 6.36 (s, 1H), 3.86 (bm, 2H), 3.39 (m, 2H), 3.23 (s, 3H), 2.88 (bd, 1H), 2.72 (bm, 3H), 2.44 (bt, 1H), 2.31 (s, 3H), 2.31 (bm, 1H), 1.53 (m, 2H). HRMS (ES) exact mass M+H calcd for C19H22F2N4OS 393.1561; found 393.1554.

後処理

  1. temperatureHeat
  2. temperatureallow cooling to ambient temperature
  3. customRemove most of the organic portion under reduced pressure
  4. custompartition the residue between ethyl acetate (450 mL) and aqueous saturated ammonium chloride solution (450 mL)
  5. customSeparate the layers
  6. extractionextract the aqueous layer with ethyl acetate (3×200 mL)
  7. extractionExtract the combined organic layers with brine (3×200 mL)
  8. concentrationConcentrate the organic layer under reduced pressure
  9. customPurify the crude product by flash chromatography
  10. washeluting with 90:10/methylene chloride

出典と根拠

ORDレコード
ord-0d4da37c18ff425c8a3ec5f2ea38cf98
出典データセット
uspto-grants-2008_06
特許番号
US07384934B2

関連ノート

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