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Hydrochloric Acid → 6-[3-({[3-(1-Cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylic acid

HRID 455234
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HRID 455234 반응식
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([C:12]([NH:14][C:15]2[CH:16]=[C:17]([CH:38]=[CH:39][CH:40]=2)[O:18][C:19]2[CH:33]=[CH:32][C:22]3[N:23]=[C:24]([NH:26][C:27]([CH:29]4[CH2:31][CH2:30]4)=[O:28])[S:25][C:21]=3[C:20]=2[C:34]([O:36]C)=[O:35])=[O:13])[CH:9]=[CH:10][CH:11]=1)([CH3:5])[CH3:4])#[N:2].O.[OH-].[Li+].Cl>O1CCCC1.CO.O.C(OCC)(=O)C>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([C:12]([NH:14][C:15]2[CH:16]=[C:17]([CH:38]=[CH:39][CH:40]=2)[O:18][C:19]2[CH:33]=[CH:32][C:22]3[N:23]=[C:24]([NH:26][C:27]([CH:29]4[CH2:30][CH2:31]4)=[O:28])[S:25][C:21]=3[C:20]=2[C:34]([OH:36])=[O:35])=[O:13])[CH:9]=[CH:10][CH:11]=1)([CH3:5])[CH3:4])#[N:2]
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참가 물질

8

반응물 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 59454479Methyl 6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylate

생성물 1

HCID 594544926-[3-({[3-(1-Cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylic acid수율 54.4%

시약·촉매·용매 4

HCID 887Methanol용매
HCID 962Water용매
HCID 8028Tetrahydrofuran용매2회
HCID 8857Ethyl Acetate용매

실험 절차

Methyl 6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylate (570 mg, 1.02 mmol) produced in Example 46(iv) was dissolved in a mixed solvent of tetrahydrofuran (6 mL)/methanol (2 mL)/water (2 mL), lithium hydroxide monohydrate (150 mg, 3.66 mmol) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was neutralized with 1N hydrochloric acid, diluted with ethyl acetate (100 mL)/tetrahydrofuran (100 mL) and washed with water (100 mL). The organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/n-hexane to give the title compound (300 mg, 54%) as a white powder.

후처리

  1. additionwas added
  2. washwashed with water (100 mL)
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90)
  5. concentrationthe obtained solution was concentrated under reduced pressure
  6. customThe residue was crystallized from ethyl acetate/n-hexane

출처 및 근거

ORD 기록
ord-96c7eb76fc824dcb982f4808ee1be398
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08497274B2

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