Ethylenediamine → HCID 58180971, compound

HRID 1772774Notes

Reaction equation

HRID 1772774 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].Cl.[NH:13]1[CH2:18][CH2:17][CH:16]([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])[CH2:15][CH2:14]1.C(N(CC)CC)C.C(Cl)Cl.FC(F)(F)C(O)=O.C(N)CN>C(#N)C.CO>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([N:13]1[CH2:18][CH2:17][CH:16]([CH2:19][CH:20]([N:24]2[CH:28]=[C:27]([C:29]3[C:30]4[CH:37]=[CH:36][NH:35][C:31]=4[N:32]=[CH:33][N:34]=3)[CH:26]=[N:25]2)[CH2:21][C:22]#[N:23])[CH2:15][CH2:14]1)=[O:5]

Participants

9

Reactant 6

HCID 3301EthylenediamineHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 5880812,4-Difluorobenzoyl chlorideHCID 67054933HCID 67054933, compound

Product 1

HCID 58180971HCID 58180971, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

2,4-Difluorobenzoyl chloride (110 mg, 0.621 mmol), 4-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride (from example 5, step 4; 0.26 g, 0.52 mmol), and triethylamine (216 μL, 0.00155 mol) were dissolved in acetonitrile (2.5 mL). The mixture was stirred at RT for 1 h. Solvents were evaporated. The crude product was treated with DCM (3 mL, 0.05 mol) and trifluoroacetic acid (3 mL, 0.04 mol) for 30 min, and evaporated to dryness under reduced pressure. To the resultant residue was added methanol (5 mL) and ethylenediamine (0.5 mL, 0.007 mol). The reaction mixture was stirred at RT for 30 min, and concentrated 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 60 mL/min) to give the desired product. LCMS calculated for C25H24F2N7O(M+H)+: m/z=476.2; Found: 476.0. 1H NMR (400 MHz, CD3OD): δ 8.96 (1H, d, J=10.0 Hz), 8.87 (1H, s), 8.51 (1H, s), 7.84 (1H, m), 7.38 (1H, m), 7.26 (1H, m), 7.06 (2H, m), 4.96 (1H, m), 4.59 (1H, m), 3.49 (2H, m), 3.15 (2H, m), 2.74 (1H, m), 2.23 (2H, m), 2.03 (1H, m), 1.86 (2H, m), 1.39 (1H, m), 1.28 (1H, m) ppm.

Workup

  1. customSolvents were evaporated
  2. customevaporated to dryness under reduced pressure
  3. stirringThe reaction mixture was stirred at RT for 30 min
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified on RP-HPLC (XBridge C-18 Column
  6. washeluting with a gradient of acetonitrile/water containing 0.15% NH4OH, at flow rate 60 mL/min)

Sources & evidence

ORD record
ord-f6a2e8f4cbe34d9f8a5468542a256f77
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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