4-Toluenesulfonyl chloride → 2-Chloro-4-fluoro-N-((2R,4R)-3-(2-methyl-piperidin-4-ylamino)-phenyl)-benzamide hydrochloride

HRID 1591898Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1591898
C(OC([N:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:31])[C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[Cl:30])[CH:16]=2)[CH2:10][C@H:9]1[CH3:32])=O)(C)(C)C.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[Cl-].[NH4+]>C1(C)C=CC=CC=1.CO>[ClH:30].[Cl:30][C:24]1[CH:25]=[C:26]([F:29])[CH:27]=[CH:28][C:23]=1[C:22]([NH:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([NH:14][C@@H:11]2[CH2:12][CH2:13][NH:8][C@H:9]([CH3:32])[CH2:10]2)[CH:16]=1)=[O:31]

Komponenten

6

Edukt 3

HCID 73974-Toluenesulfonyl chlorideHCID 25517Ammonium ChlorideHCID 58997392(2R,4R)-4-(3-(2-Chloro-4-fluoro-benzoylamino)-phenylamino)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 669388242-Chloro-4-fluoro-N-((2R,4R)-3-(2-methyl-piperidin-4-ylamino)-phenyl)-benzamide hydrochlorideAusbeute 77,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittel2×HCID 1140TolueneLösungsmittel

Versuchsvorschrift

Dissolve (2R,4R)-4-(3-(2-chloro-4-fluoro-benzoylamino)-phenylamino)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester (Preparation 59, 119 mg, 0.258 mmol) in toluene (5 mL). Add p-toluenesulfonyl chloride (152 mg, 0.798 mmol) and heat to 100° C. for 3 hr. Cool to room temperature and load onto an SCX column with methanol. Wash the column with methanol, flush with 2M ammonia in methanol, and concentrate in vacuo. Purify by column chromatography (0%–10% 2M NH3 in methanol/CH2Cl2) to yield an oil. Make the hydrochloride salt by sonication with one equivalent of ammonium chloride dissolved in methanol to yield 40 mg (39%) of the title compound: mass spectrum (ion spray): m/z=362.1 (M+1); 1H NMR δ (D2O/DCl, ppm) 7.78 (s, 1H), 7.49 (m, 3H), 7.21 (t, J=9.0 Hz, 18.0 Hz, 2H), 7.07 (t, J=9.0 Hz, 18.0 Hz, 1H), 3.83 (m, 1H), 3.45 (m, 1H), 3.20 (m, 1H), 2.95 (m, 1H), 2.18 (m, 2H), 1.80 (m, 1H), 1.65 (m, 1H), 1.20 (d, J=6.6 Hz, 3H); mp 182–5° C.

Aufarbeitung

  1. washWash the column with methanol
  2. customflush with 2M ammonia in methanol
  3. concentrationconcentrate in vacuo
  4. customPurify by column chromatography (0%–10% 2M NH3 in methanol/CH2Cl2)
  5. customto yield an oil

Quellen und Nachweise

ORD-Eintrag
ord-00a5bfb3334b4f5e87f129674a757a19
Quelldatensatz
uspto-grants-2007_11
Patentnummer
US07291632B2

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