Toluene → 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho [2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide

HRID 1730581노트

반응식

HRID 1730581 반응식
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C(N(CC)CC)C.[CH3:14][N:15]1[C:20]([C:21](Cl)=[O:22])=[C:19](N2CCCC2)[C:18]2[CH:29]=[CH:30][C:31]3[C:36]([C:17]=2[S:16]1(=[O:38])=[O:37])=[CH:35][CH:34]=[CH:33][CH:32]=3.CN1C=C(N2CCCC2)C2C=CC3C(C=2S1(=O)=[O:59])=CC=CC=3.C(Cl)(Cl)=O.C1(C)C=CC=CC=1>O1CCCC1>[OH:59][C:19]1[C:18]2[CH:29]=[CH:30][C:31]3[C:36]([C:17]=2[S:16](=[O:38])(=[O:37])[N:15]([CH3:14])[C:20]=1[C:21]([NH:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1)=[O:22])=[CH:35][CH:34]=[CH:33][CH:32]=3

참가 물질

8

반응물 6

HCID 1140TolueneHCID 21552-AminothiazoleHCID 6371PhosgeneHCID 8471Triethylamine2회HCID 214981112-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acidchloride-1,1-dioxideHCID 214981402-Methyl-4-(pyrrolidin-1-yl)-1lambda~6~-naphtho[2,1-e][1,2]thiazine-1,1(2H)-dione

생성물 1

HCID 547184104-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho [2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide수율 36.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of 0.9 gm (9 millimols) of 2-amino-thiazole and 0.78 gm (7.7 millimols) of triethylamine in 8 ml tetrahydrofuran was added dropwise at -40° C to a solution of 6.4 millimols of 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]1,2-thiazine-3-carboxylic acid chloride-1,1-dioxide, which was obtained by reacting 2.0 gm (6.4 millimols) of 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2-thiazine-1,1-dioxide with 4 ml of a solution (20%) of phosgene in toluene (7.7 millimols) in the presence of 0.78 gm (7.7 millimols) of triethylamine in 80 ml of tetrahydrofuran. The reaction mixture was warmed to room temperature over a period of 2 hours and afterwards stirred at room temperature for 36 hours. Ice water was then added to the mixture, and the aqueous mixture was extracted several times with ethylene chloride. The combined organic phases were evaporated, and the residue was refluxed with 2 N hydrochloricacid for 2 hours. After cooling, the mixture was extracted with ethylene chloride, the organic phase was evaporated, and the residue was purified by chromatography on silicagel, using chloroform/methanol (ratio by volume10:1) as the eluant. The eluates yielded 0.9 gm (35% of theory) of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho [2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide, m.p. 248°-249° C (decomp.).

후처리

  1. customwhich was obtained
  2. extractionthe aqueous mixture was extracted several times with ethylene chloride
  3. customThe combined organic phases were evaporated
  4. temperaturethe residue was refluxed with 2 N hydrochloricacid for 2 hours
  5. temperatureAfter cooling
  6. extractionthe mixture was extracted with ethylene chloride
  7. customthe organic phase was evaporated
  8. customthe residue was purified by chromatography on silicagel

출처 및 근거

ORD 기록
ord-d82573f591ba4a09bedfb8d3342f2196
출처 데이터셋
uspto-grants-1976_11
특허 번호
US03992535

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