4-Toluenesulfonyl chloride → Toluene-4-sulfonic acid 3-[4-(1-tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)-phenyl]-1-methylpropyl ester

HRID 1751838노트

반응식

HRID 1751838 반응식
C([N:5]1[C:10](=[O:11])[C:9]([Cl:12])=[C:8]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH:23]([OH:25])[CH3:24])=[CH:17][CH:16]=2)[CH:7]=[N:6]1)(C)(C)C.[C:26]1([CH3:36])[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>N1C=CC=CC=1.C(OCC)(=O)C>[C:15]([CH:14]([O:13][C:8]1[CH:7]=[N:6][NH:5][C:10](=[O:11])[C:9]=1[Cl:12])[C:15]1[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][CH:23]([O:25][S:32]([C:29]2[CH:30]=[CH:31][C:26]([CH3:36])=[CH:27][CH:28]=2)(=[O:34])=[O:33])[CH3:24])=[CH:19][CH:20]=1)([CH3:20])([CH3:16])[CH3:14]

참가 물질

5

반응물 2

HCID 73974-Toluenesulfonyl chlorideHCID 596786062-tert-butyl-4-chloro-5-[4-(3-hydroxybutyl)benzyloxy]-2H-pyridazin-3-one

생성물 1

HCID 86600388Toluene-4-sulfonic acid 3-[4-(1-tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)-phenyl]-1-methylpropyl ester수율 52%

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of the product of Example 7B (200 mg, 0.548 mmol) in pyridine (10 mL) was added p-toluenesulfonyl chloride (209 mg, 1.096 mmol). The reaction was stirred at room temperature overnight under nitrogen atmosphere. Monitoring by LC-MS showed a 1:1 mixture of starting material and product. The reaction was diluted with ethyl acetate and washed with 5% CuSO4 until a light blue aqueous solution was maintained. The organic layer was then dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash column chromatography (3:1 hexane:ethyl acetate to 100% ethyl acetate) to recover the starting material (90 mg) and the product as a clear oil (74 mg, 47% yield based on recovered starting material). 1H NMR (600 MHz, CDCl3): 7.80 (d, 2H, J=8.3 Hz), 7.72 (s, 1H), 7.33 (d, 2H, J=8.0 Hz), 7.30 (d, 2H, J=8.1 Hz), 7.13 (d, 2H, J=8.1 Hz), 5.27 (s, 2H), 4.66 (m, 1H), 2.65 (m, 1H), 2.54 (m, 1H), 2.45 (s, 3H), 1.94 (m, 1H), 1.81 (m, 1H), 1.63 (s, 9H), 1.26 (s, 3H).

후처리

  1. additiona 1:1 mixture of starting material and product
  2. washwashed with 5% CuSO4 until a light blue aqueous solution
  3. temperaturewas maintained
  4. dry with materialThe organic layer was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash column chromatography (3:1 hexane:ethyl acetate to 100% ethyl acetate)
  8. customto recover the starting material (90 mg)

출처 및 근거

ORD 기록
ord-50f45c0483554b61977e17edf3b2e11b
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09161997B2

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