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

HRID 1716918Notes

Reaction equation

HRID 1716918 reaction equation
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]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 25517Ammonium ChlorideHCID 58997317HCID 58997317, compound

Product 1

HCID 669390312-Chloro-4-fluoro-N-((2S,4S)-3-(2-methyl-piperidin-4-ylamino)-phenyl)-benzamide hydrochlorideYield 127.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 1140TolueneSolvent

Procedure

Dissolve (2S,4S)-4-(3-(2-chloro-4-fluoro-benzoylamino)-phenylamino)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester (Preparation 58, 137 mg, 0.296 mmol) in toluene (10 mL). Add p-toluenesulfonyl chloride (152 mg, 0.798 mmol) and heat to 100° C. for 2 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%-15% 2 M 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 75 mg (64%) 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 Hz, 18 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 202° C. (dec.).

Workup

  1. washWash the column with methanol
  2. customflush with 2M ammonia in methanol
  3. concentrationconcentrate in vacuo
  4. customPurify by column chromatography (0%-15% 2 M NH3 in methanol/CH2Cl2)
  5. customto yield an oil

Sources & evidence

ORD record
ord-700e4c8086244c7780ad6d739a1e7aa5
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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