Acetyl chloride → HCID 56598362, compound

HRID 711230Notes

Reaction equation

HRID 711230 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([CH3:30])[CH:25]=1)[CH2:5][NH:6][C:7](=[O:20])[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[N:10][CH:9]=1.CCN(C(C)C)C(C)C.[C:40](Cl)(=[O:42])[CH3:41]>ClCCl.C(OCC)(=O)C>[C:40]([N:17]1[CH2:18][CH2:19][N:14]([C:11]2[CH:12]=[CH:13][C:8]([C:7]([NH:6][CH2:5][C:4]3[CH:21]=[CH:22][C:23]([C:24]4[CH:29]=[CH:28][N:27]=[C:26]([CH3:30])[CH:25]=4)=[C:2]([F:1])[CH:3]=3)=[O:20])=[CH:9][N:10]=2)[CH2:15][CH2:16]1)(=[O:42])[CH3:41]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 67208671HCID 67208671, compound

Product 1

HCID 56598362HCID 56598362, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of crude N-(3-fluoro-4-(2-methylpyridin-4-yl)benzyl)-6-(piperazin-1-yl)nicotinamide 20-3 (10 mg, 0.025 mmol) and DIEA (21.8 μL, 0.125 mmol) in dichloromethane (1.0 mL) was added acetyl chloride (3.6 μL, 0.05 mmol), and the solution was stirred 30 minutes at room temperature. The solution was diluted with ethyl acetate (30 mL) and washed with 10% Na2CO3 aqueous solution and water. After the organic phase was dried over Na2SO4, the solvent was evaporated under reduced pressure and the residue subjected to preparative reverse phase HPLC to give 6-(4-acetylpiperazin-1-yl)-N-(3-fluoro-4-(2-methylpyridin-4-yl)benzyl)nicotinamide 20 as a solid. MS m/z 448.2 (M+1). 1H NMR 400 MHz (CDCl3) δ 8.63 (d, 1H), 8.54 (d, 1H), 7.98 (dd, 1H), 7.42 (dd, 1H), 7.33 (bs, 1H), 7.29-7.25 (m, 1H), 7.22 (dd, 1H), 7.16 (dd, 1H), 6.64 (d, 1H), 6.61 (t, 1H), 4.67 (d, 2H), 3.78-3.70 (m, 4H), 3.65-3.54 (m, 4H), 2.61 (s, 3H), 2.14 (s, 3H).

Workup

  1. washwashed with 10% Na2CO3 aqueous solution and water
  2. dry with materialAfter the organic phase was dried over Na2SO4
  3. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bf1cda535eed4b9aa53185539f4b4c9d
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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