Hydrochloric Acid → N-(3-Chloro-phenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide

HRID 1730580Notes

Reaction equation

HRID 1730580 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH3:9][N:10]1[C:15]([C:16](Cl)=[O:17])=[C:14](N2CCCC2)[C:13]2[CH:24]=[CH:25][C:26]3[C:31]([C:12]=2[S:11]1(=[O:33])=[O:32])=[CH:30][CH:29]=[CH:28][CH:27]=3.CN1C=C(N2CCCC2)C2C=CC3C(C=2S1(=O)=[O:54])=CC=CC=3.C(Cl)(Cl)=O.C(N(CC)CC)C.Cl>O1CCCC1.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:16]([C:15]2[N:10]([CH3:9])[S:11](=[O:33])(=[O:32])[C:12]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24][C:13]=3[C:14]=2[OH:54])=[O:17])[CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6371PhosgeneHCID 79323-ChloroanilineHCID 8471TriethylamineHCID 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 54695958N-(3-Chloro-phenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxideYield 49%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 0.51 gm (44 millimols) of 3-chloro-aniline in 8 ml of dry tetrahydrofuran was added dropwise to a solution of 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acidchloride-1,1-dioxide in tetrahydrofuran at -40° C. The latter solution was obtained by reacting 0.63 gm (2 millimols) of 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2-thiazine-1,1-dioxide with 0.25 gm (2.5 millimols) of phosgene and 0.25 gm (2.5 millimols) of triethylamine in 16 ml of anhydrous tetrahydrofuran, as described below. The reaction mixture was allowed to warm to room temperature for 24 hours.Then, ice water was added, and the aqueous mixture was extracted twice withmethylene chloride. The combined organic phases were washed twice with water, dried over sodium sulfate and evaporated in vacuo. Petroleum ether was added to the residue, whereby crude crystalline N-(3-chloro-phenyl)-2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2 -thiazine-3-carboxamide-1,1-dioxide, m.p. 163°-167° C (decomp.), was obtained, which was immediately dissolved in 6 ml of aceticacid, and 2 N hydrochloric acid were added to the solution. The mixture washeated at 100° for 30 minutes, allowed to cool, and 50 ml of ice water were added. The precipitated product was filtered off, dried and recrystallized from ethylene chloride/petroleum ether, yielding 410 mgm (49% of theory) of N-(3-chloro-phenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide, m.p. 247°-248° C (decomp.).

Workup

  1. customThe latter solution was obtained
  2. extractionthe aqueous mixture was extracted twice withmethylene chloride
  3. washThe combined organic phases were washed twice with water
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. additionPetroleum ether was added to the residue, whereby crude crystalline N-(3-chloro-phenyl)-2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2 -thiazine-3-carboxamide-1,1-dioxide, m.p. 163°-167° C (decomp.)
  7. customwas obtained
  8. temperatureto cool
  9. filtrationThe precipitated product was filtered off
  10. customdried
  11. customrecrystallized from ethylene chloride/petroleum ether

Sources & evidence

ORD record
ord-f909ad901ca74d1dabcc7742e0f2d88c
Source dataset
uspto-grants-1976_11
Patent number
US03992535

Reaction notes

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