Ethylenediamine → 4-[(4-{3-cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperazin-1-yl)carbonyl]benzonitrile

HRID 1772767Notes

Reaction equation

HRID 1772767 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)#[N:2].Cl.[N:13]1([CH2:19][CH:20]([N:24]2[CH:28]=[C:27]([C:29]3[C:30]4[CH:37]=[CH:36][N:35](COCC[Si](C)(C)C)[C:31]=4[N:32]=[CH:33][N:34]=3)[CH:26]=[N:25]2)[CH2:21][C:22]#[N:23])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(N(CC)CC)C.FC(F)(F)C(O)=O.C(N)CN>C(#N)C.CO.C(Cl)Cl>[C:22]([CH2:21][CH:20]([N:24]1[CH:28]=[C:27]([C:29]2[C:30]3[CH:37]=[CH:36][NH:35][C:31]=3[N:32]=[CH:33][N:34]=2)[CH:26]=[N:25]1)[CH2:19][N:13]1[CH2:14][CH2:15][N:16]([C:7]([C:6]2[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)=[O:8])[CH2:17][CH2:18]1)#[N:23]

Participants

9

Reactant 5

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 801724-Cyanobenzoyl chlorideHCID 670549114-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride

Product 1

HCID 509956414-[(4-{3-cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperazin-1-yl)carbonyl]benzonitrile

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

4-Cyanobenzoyl chloride (7.91 mg, 0.0478 mmol), 4-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride (from example 1, step 4; 0.02 g, 0.0398 mol) and triethylamine (16.6 μL, 0.119 mmol) were dissolved in acetonitrile (0.2 mL). The mixture was stirred at RT for 1 h. Solvents were evaporated and the crude product was treated with DCM (0.2 mL) and trifluoroacetic acid (0.2 mL, 0.002 mol) for 30 min. The reaction mixture was concentrated under reduced pressure. To the residue was added methanol (1 mL) and ethylenediamine (0.1 mL, 0.001 mol) and the resultant mixture was stirred at RT for 30 min and evaporated under reduced pressure. The residue was purified on RP-HPLC (XBridge C-18 Column, eluting with a gradient of acetonitrile/water containing 0.15% NH4OH, at flow rate 30 mL/min) to give the desired product. LCMS calculated for C25H24N9O(M+H)+: m/z=466.2; Found 466.0.

Workup

  1. customSolvents were evaporated
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customevaporated under reduced pressure
  4. customThe residue was purified on RP-HPLC (XBridge C-18 Column
  5. washeluting with a gradient of acetonitrile/water containing 0.15% NH4OH, at flow rate 30 mL/min)

Sources & evidence

ORD record
ord-b2d251735f174690aec23cdcf39e8e96
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

Loading…