Chloroacetyl chloride → HCID 58254974, compound

HRID 1897685Notes

Reaction equation

HRID 1897685 reaction equation
[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1.Cl[CH2:31][C:32](Cl)=[O:33].C(N(CC)CC)C.[CH3:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[C:10]([F:22])=[CH:11][C:12]([CH:16]3[CH2:17][CH2:18][N:19]([C:32](=[O:33])[CH2:31][N:46]4[CH2:47][CH2:48][N:43]([CH3:42])[CH2:44][CH2:45]4)[CH2:20][CH2:21]3)=[C:13]([CH3:15])[CH:14]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 446126165-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 58254974HCID 58254974, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To the solution of 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (100.0 mg, 0.24 mmol) in 4 mL of DCM was added 2-chloroacetylchloride (23.0 uL, 0.29 mmol) and triethylamine (67.0 uL, 0.48 mmol) sequentially. The reaction was stirred at room temperature for 1 h then washed by brine. The organic extract was dried over Na2SO4, followed by concentration in vacuo to afford a crude product. The crude product was mixed with 1-methylpiperazine (116.0 mg, 1.16 mmol) in 3 mL of DMF and the reaction was stirred overnight at room temperature. The reaction mixture was purified by preparative HPLC to afford 1-(4-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-5-fluoro-2-methylphenyl)piperidin-1-yl)-2-(4-methylpiperazin-1-yl)ethanone. ESMS m/z 556.3 (M+H+).

Workup

  1. washthen washed by brine
  2. extractionThe organic extract
  3. dry with materialwas dried over Na2SO4
  4. concentrationfollowed by concentration in vacuo
  5. customto afford a crude product
  6. stirringthe reaction was stirred overnight at room temperature
  7. customThe reaction mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-22c09e83e1f3494294b6e9cde38f9cf3
Source dataset
uspto-grants-2013_08
Patent number
US08519129B2

Reaction notes

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