Ethylenediamine → HCID 58180949, compound

HRID 1772776Notes

Reaction equation

HRID 1772776 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.Cl.[NH:12]1[CH2:17][CH2:16][CH:15]([CH2:18][CH:19]([N:23]2[CH:27]=[C:26]([C:28]3[C:29]4[CH:36]=[CH:35][N:34](COCC[Si](C)(C)C)[C:30]=4[N:31]=[CH:32][N:33]=3)[CH:25]=[N:24]2)[CH2:20][C:21]#[N:22])[CH2:14][CH2:13]1.C(N(CC)CC)C.FC(F)(F)C(O)=O.C(N)CN>C(#N)C.CO.C(Cl)Cl>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:12]2[CH2:17][CH2:16][CH:15]([CH2:18][CH:19]([N:23]3[CH:27]=[C:26]([C:28]4[C:29]5[CH:36]=[CH:35][NH:34][C:30]=5[N:31]=[CH:32][N:33]=4)[CH:25]=[N:24]3)[CH2:20][C:21]#[N:22])[CH2:14][CH2:13]2)=[O:7])=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 678794-Fluorobenzoyl chlorideHCID 67054933HCID 67054933, compound

Product 1

HCID 58180949HCID 58180949, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

4-Fluoro benzoyl chloride (94.7 mg, 0.597 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; 0.250 g, 0.498 mmol), and triethylamine (208 μL, 0.00149 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) 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) and the resulting mixture was stirred at RT for 30 min. After being 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 C25H25FN7O(M+H)+: m/z=458.2; Found: 458.0. NMR (300 MHz, CD3OD) δ 9.01 (1H, s), 8.90 (1H, s), 8.54 (1H, s), 7.89 (1H, d, J=3.6 Hz), 7.42 (2H, m), 7.31 (1H, d, J=3.6 Hz), 7.17 (2H, m), 4.98 (1H, m), 4.55 (1H, m), 3.52 (2H, m), 3.16 (2H, m), 2.73 (1H, m), 2.25 (2H, m), 2.03 (1H, m), 1.88 (2H, m), 1.38 (1H, m), 1.28 (1H, m) ppm.

Workup

  1. customSolvents were evaporated
  2. customevaporated to dryness under reduced pressure
  3. stirringthe resulting mixture was stirred at RT for 30 min
  4. concentrationAfter being concentrated 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-7b49f25c526a4f53ae1af432d2a47952
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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