Chlorosuccinimide → N-(1-(5-chloro-4-(pyridin-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanesulfonamide

HRID 2172870Notes

Reaction equation

HRID 2172870 reaction equation
C1C(=O)N([Cl:8])C(=O)C1.[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([N:21]2[CH2:26][CH2:25][CH:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:23][CH2:22]2)[N:16]=1>CC(O)=O>[Cl:8][C:20]1[C:15]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][N:9]=2)=[N:16][C:17]([N:21]2[CH2:22][CH2:23][CH:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:25][CH2:26]2)=[N:18][CH:19]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 67508213N-(1-(4-(pyridin-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanesulfonamide

Product 1

HCID 67509701N-(1-(5-chloro-4-(pyridin-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanesulfonamideYield 29%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

NCS (370 mg, 2.83 mmol) was added to a solution of N-(1-(4-(pyridin-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanesulfonamide (180 mg, 2.36 mmol) in AcOH (10 mL) at 60° C. and the reaction solution was stirred for 2 h. LC-MS indicated the reaction was almost complete. The reaction solution was concentrated and purified by chromatography, eluted with CH2Cl2:MeOH (6:1) to give crude product, which was further purified by Prep-HPLC to give title compound (251 mg, 29%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.68-8.70 (d, 1H), 8.29 (s, 1H), 7.75-7.79 (m, 1H), 7.70-7.72 (d, 1H), 7.31-7.34 (t, 1H), 4.60-4.63 (d, 2H), 4.18-4.20 (d, 1H), 3.53-3.57 (t, 1H), 2.94 (s, 3H), 1.99-2.02 (d, 1H), 1.39-1.49 (m, 1H); m/z for C15H18ClN5O2S 390.1 (M+Na)+.

Workup

  1. concentrationThe reaction solution was concentrated
  2. custompurified by chromatography
  3. washeluted with CH2Cl2:MeOH (6:1)
  4. customto give crude product, which
  5. customwas further purified by Prep-HPLC

Sources & evidence

ORD record
ord-739a9258a8a045bbb2195662fb81f039
Source dataset
uspto-grants-2015_06
Patent number
US09056865B2

Reaction notes

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