Acetic Anhydride → N-(5-(4-chlorophenyl)-2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenylethynyl}pyridin-3-yl)acetamide

HRID 734851Notes

Reaction equation

HRID 734851 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]([NH2:39])[C:18]([C:21]#[C:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH:35]([CH3:38])[CH2:34][CH2:33]4)=[CH:25][CH:24]=3)=[N:19][CH:20]=2)=[CH:11][CH:10]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]([NH:39][C:1](=[O:3])[CH3:2])[C:18]([C:21]#[C:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH:35]([CH3:38])[CH2:34][CH2:33]4)=[CH:25][CH:24]=3)=[N:19][CH:20]=2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 114960185-(4-Chlorophenyl)-2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenylethynyl}pyridin-3-ylamine

Product 1

HCID 57845319N-(5-(4-chlorophenyl)-2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenylethynyl}pyridin-3-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

125 μL (1.345 mmol) of acetic anhydride was added at RT to a solution of 100 mg (0.224 mmol) of 5-(4-chlorophenyl)-2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenylethynyl}pyridin-3-ylamine (Example 19.1d) and 62 μL (0.448 mmol) of triethylamine in 5 mL of DCM and the mixture was refluxed for 72 hours. The reaction mixture was diluted with DCM, and the organic phase was washed with saturated aqueous sodium bicarbonate solution, water, and 12% aqueous HCl, dried over magnesium sulfate, and evaporated down in vacuo. The residue was triturated with DIPE, and the precipitate was filtered off and dried in vacuo. The crude product was purified by HPLC-MS (Zorbax Stable Bond C18, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v). Yield: 23 mg (21% of theoretical); C29H30ClN3O2 (M=488.020); calc.: molpeak (M+H)+: 488/490 (Cl); found: molpeak (M+H)+: 488/490 (Cl); HPLC-MS: 5.01 minutes (method B).

Workup

  1. temperaturethe mixture was refluxed for 72 hours
  2. washthe organic phase was washed with saturated aqueous sodium bicarbonate solution, water, and 12% aqueous HCl
  3. dry with materialdried over magnesium sulfate
  4. customevaporated down in vacuo
  5. customThe residue was triturated with DIPE
  6. filtrationthe precipitate was filtered off
  7. customdried in vacuo
  8. customThe crude product was purified by HPLC-MS (Zorbax Stable Bond C18, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v)
  9. custom5.01 minutes (method B)

Sources & evidence

ORD record
ord-504d4f93d612424eb6d5a2599ea51cd9
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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