Propionic Acid → 4-Fluorobenzenesulfonic acid 2-propionylaminobenzothiazol-6-yl ester

HRID 1867991노트

반응식

HRID 1867991 반응식
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][S:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[CH:8]=[CH:7][C:5]=2[N:6]=1.[C:22](O)(=[O:25])[CH2:23][CH3:24].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C>CN(C)C=O.CS(C)=O>[C:22]([NH:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][S:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)(=[O:13])=[O:14])[CH:8]=[CH:7][C:5]=2[N:6]=1)(=[O:25])[CH2:23][CH3:24]

참가 물질

7

반응물 4

HCID 1032Propionic AcidHCID 7912DiisopropylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579808144-Fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester2회

생성물 1

HCID 579808244-Fluorobenzenesulfonic acid 2-propionylaminobenzothiazol-6-yl ester수율 69.2%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 6228Dimethylformamide용매

실험 절차

A solution of 4-fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester (intermediate 16) (500 mg, 1.14 mmol), propionic acid (253 mg, 3.42 mmol), HBTU (1.23 g, 3.42 mmol) and N,N-diisopropylamine (737 mg, 5.7 mmol) in 6.5 ml of dimethylformamide is stirred overnight at room temperature. The reaction medium is evaporated to dryness. The dry residue is extracted twice with 50 ml of ethyl acetate and washed with water. The organic phase is then washed with saturated sodium chloride solution. The organic phase is dried over magnesium sulfate and then evaporated. The oil obtained is dissolved in 35 ml of dimethyl sulfoxide and then purified 7 times by preparative HPLC on a Nucléodur C18, 100′10 μm reverse-phase column with a gradient over 52 minutes of 5% to 95% acetonitrile supplemented with 0.07% trifluoroacetic acid in water, supplemented with 0.07% trifluoroacetic acid. The flow rate is 70 ml/min. The fractions containing the clean product are concentrated to give 300 mg of 4-fluorobenzenesulfonic acid 2-propionylaminobenzothiazol-6-yl ester in a yield of 69%.

후처리

  1. customThe reaction medium is evaporated to dryness
  2. extractionThe dry residue is extracted twice with 50 ml of ethyl acetate
  3. washwashed with water
  4. washThe organic phase is then washed with saturated sodium chloride solution
  5. dry with materialThe organic phase is dried over magnesium sulfate
  6. customevaporated
  7. customThe oil obtained
  8. custompurified 7 times by preparative HPLC on a Nucléodur C18, 100′10 μm reverse-phase column with a gradient over 52 minutes of 5% to 95% acetonitrile
  9. additionThe fractions containing the clean product
  10. concentrationare concentrated

출처 및 근거

ORD 기록
ord-ad8249cdd216415aa205fd3ade20c991
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07632952B2

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