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

HRID 1730580노트

반응식

HRID 1730580 반응식
[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

참가 물질

9

반응물 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

생성물 1

HCID 54695958N-(3-Chloro-phenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide수율 49%

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 8028Tetrahydrofuran용매3회

실험 절차

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.).

후처리

  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

출처 및 근거

ORD 기록
ord-f909ad901ca74d1dabcc7742e0f2d88c
출처 데이터셋
uspto-grants-1976_11
특허 번호
US03992535

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