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

반응식

HRID 131451 반응식
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

참가 물질

5

반응물 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

생성물 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]azulene수율 66.4%

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
115 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0d4da37c18ff425c8a3ec5f2ea38cf98
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384934B2

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