Diisopropylethylamine → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(3-fluoro-piperidin-1-yl)-4-(4-methyl-piperazin-1-yl)-phenyl]-amide

HRID 646952Notes

Reaction equation

HRID 646952 reaction equation
[K+].[C:2]([C:4]1[N:5]=[C:6]([C:17]([O-:19])=O)[N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[CH:8]=1)#[N:3].CCN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[F:53][CH:54]1[CH2:59][CH2:58][CH2:57][N:56]([C:60]2[CH:65]=[C:64]([N:66]3[CH2:71][CH2:70][N:69]([CH3:72])[CH2:68][CH2:67]3)[CH:63]=[CH:62][C:61]=2[NH2:73])[CH2:55]1>C(Cl)Cl>[F:53][CH:54]1[CH2:59][CH2:58][CH2:57][N:56]([C:60]2[CH:65]=[C:64]([N:66]3[CH2:67][CH2:68][N:69]([CH3:72])[CH2:70][CH2:71]3)[CH:63]=[CH:62][C:61]=2[NH:73][C:17]([C:6]2[N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:15])[CH3:16])[CH:8]=[C:4]([C:2]#[N:3])[N:5]=2)=[O:19])[CH2:55]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 586385442-(3-Fluoro-piperidin-1-yl)-4-(4-methyl-piperazin-1-yl)-phenylamineHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 586385284-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(3-fluoro-piperidin-1-yl)-4-(4-methyl-piperazin-1-yl)-phenyl]-amideYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A suspension of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 3, step (d), 48 mg, 0.16 mmol) in CH2Cl2 (5 mL) was treated with DIEA (68 μL, 0.39 mmol) and PyBroP (0.11 g, 0.24 mmol). The reaction stirred at room temperature for 10 min. A solution of 2-(3-fluoro-piperidin-1-yl)-4-(4-methyl-piperazin-1-yl)-phenylamine (as prepared in the previous step, 46 mg, 0.16 mmol) in CH2Cl2 (4 mL) was added, and the reaction was stirred at room temperature for 19.5 h. The reaction was diluted with CH2Cl2 and washed with saturated aqueous NaHCO3 and water. The organic layer was dried over MgSO4 and concentrated in vacuo to afford the title compound (62 mg, 70%) as an off-white solid, which was used directly in the next reaction. LC-MS (ESI, m/z): Calcd. for C27H40FN7O2Si, 542.3 (M+H), found 542.4.

Workup

  1. additionwas added
  2. stirringthe reaction was stirred at room temperature for 19.5 h
  3. washwashed with saturated aqueous NaHCO3 and water
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-356257e2a7414f6f9355eb6559fdf8ca
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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