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

HRID 1730581Notes

Reaction equation

HRID 1730581 reaction equation
[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

Participants

8

Reactant 6

HCID 1140TolueneHCID 21552-AminothiazoleHCID 6371PhosgeneHCID 8471Triethylamine2×HCID 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.).

Workup

  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

Sources & evidence

ORD record
ord-d82573f591ba4a09bedfb8d3342f2196
Source dataset
uspto-grants-1976_11
Patent number
US03992535

Reaction notes

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