Hydrochloric Acid → cis-3-[4'-(6-Chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acid

HRID 907762노트

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HRID 907762 반응식
C[O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)=[O:12])[CH2:6]1)=[O:4].Cl[C:27]1[S:28][C:29]2[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:30]=2[N:31]=1.[OH-].[Na+].Cl>C(O)CCC.Cl.O1CCOCC1.CO>[Cl:36][C:34]1[CH:33]=[CH:32][C:30]2[N:31]=[C:27]([NH:25][C:22]3[CH:21]=[CH:20][C:19]([C:16]4[CH:17]=[CH:18][C:13]([C:11]([C@@H:7]5[CH2:8][CH2:9][CH2:10][C@H:5]([C:3]([OH:4])=[O:2])[CH2:6]5)=[O:12])=[CH:14][CH:15]=4)=[CH:24][CH:23]=3)[S:28][C:29]=2[CH:35]=1

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 771762,6-Dichlorobenzothiazole2회HCID 235493393-(4'-Amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester

생성물 1

HCID 11698838cis-3-[4'-(6-Chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acid수율 23.4%

시약·촉매·용매 4

HCID 313Hydrochloric Acid촉매2회HCID 2631-Butanol용매HCID 887Methanol용매HCID 312751,4-Dioxane용매2회

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온도
90 °C

실험 절차

To a solution of 3-(4′-amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester (100 mg, 0.3 mmol) in butanol (5 mL), 2,6-dichloro-benzothiazole (60 mg, 0.3 mmol) and 5 drops of 4 M HCl in dioxane were added, and the reaction mixture was heated at 90° C. for 5 h. An additional sample of 2,6-dichlorobenzothiazole (60 mg, 0.3 mmol) and 5 drops of 4 M HCl in dioxane were then added, and the reaction mixture was heated overnight at 90° C. The solvent was removed by rotary evaporation, the residue was dissolved in DMF (2 mL), 1 N aqueous NaOH (0.3 mL, 0.3 mmol) was added, and the mixture was heated at 75° C. overnight A solution of 1 N aqueous HCl (0.3 mL, 0.3 mmol) and methanol (5 mL) were added to the reaction mixture, and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford cis-3-[4′-(6-chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acid as a white solid (12.6 mg, yield 23.4%). 1H NMR (300 MHz, DMSO) δ 8.05 (d, 2H), 7.75-8.00 (m, 7H), 7.50 (d, 1H), 7.35 (d, 1H), 3.25 (m, 1H), 2.50 (m, 1H), 2.20-1.90 (m, 4H), 1.70-1.50 (m, 4H); LC-MS ret. time 3.99 min (method 2), m/z 491.11 (MH+).

후처리

  1. temperaturethe reaction mixture was heated overnight at 90° C
  2. customThe solvent was removed by rotary evaporation
  3. dissolutionthe residue was dissolved in DMF (2 mL)
  4. additionwere added to the reaction mixture
  5. customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

출처 및 근거

ORD 기록
ord-d350306092df444eb1083c9609cc8d6e
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08013166B2

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