Methanesulfonyl chloride → 6-(1-Methanesulfonyl-piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

HRID 1049026노트

반응식

HRID 1049026 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:25][CH:26]([CH3:28])[CH3:27])[S:9]([C:12]2[CH:13]=[N:14][C:15]([NH:18][CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[CH:16][CH:17]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40].C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:25][CH:26]([CH3:28])[CH3:27])[S:9]([C:12]2[CH:13]=[N:14][C:15]([NH:18][CH:19]3[CH2:24][CH2:23][N:22]([S:39]([CH3:38])(=[O:41])=[O:40])[CH2:21][CH2:20]3)=[CH:16][CH:17]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 867218776-(Piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

생성물 1

HCID 762841856-(1-Methanesulfonyl-piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 4-{5-[(4-fluoro-phenyl)-isobutyl-sulfamoyl]-pyridin-2-ylamino}-piperidine-1-carboxylic acid tert-butyl ester (66 mg, 130 μmol) in DCM (8 mL) was added TFA (2 mL) and the reaction was stirred at room temperature for 30 minutes. The reaction was concentrated and purified by SCX column eluting with 2M NH3 in MeOH to give 6-(piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (41 mg, 101 μmol). To a solution of 6-(piperidin-4-ylamino)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (41 mg, 101 μmol) in DCM (5 mL) was added DIPEA (35 μL, 202 μmol) followed by methane sulfonylchloride (1 mL of a 78 μL, 1 mmol solution in 10 mL of DCM) and the reaction stirred at room temperature for 30 minutes. Water and saturated NaHCO3 were then added, extracted, filtered through a phase separator, concentrated and purified by silica gel column chromatography (0-50% EtOAc in cyclohexane) to give the title compound (49 mg). 1H NMR (400 MHz, DMSO): δ 8.03 (d, J=2.52 Hz, 1H), 7.54 (d, J=7.47 Hz, 1H), 7.35 (dd, J=8.95, 2.54 Hz, 1H), 7.17 (t, J=8.01 Hz, 4H), 6.51 (d, J=8.98 Hz, 1H), 3.91 (br s, 1H), 3.51 (d, J=11.88 Hz, 2H), 3.25 (d, J=7.31 Hz, 2H), 2.86 (m, 5H), 1.97 (d, J=12.65 Hz, 2H), 1.44-1.49 (m, 2H), 0.82 (d, J=6.63 Hz, 6H). LCMS (m/z, Method B) ES+ 485.0 [M+1]+.

후처리

  1. extractionextracted
  2. filtrationfiltered through a phase separator
  3. concentrationconcentrated
  4. custompurified by silica gel column chromatography (0-50% EtOAc in cyclohexane)

출처 및 근거

ORD 기록
ord-4d8b0ad1f087420093ff7e6b05d2be6f
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382222B2

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