Ethylenediamine → HCID 58180899, compound

HRID 1772775Notes

Reaction equation

HRID 1772775 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[N: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>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([S:7]([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:9])=[O:8])=[N:3]1

Participants

9

Reactant 5

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 134744661-Methyl-1H-pyrazole-3-sulfonyl chlorideHCID 67054933HCID 67054933, compound

Product 1

HCID 58180899HCID 58180899, compoundYield 76.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

1-Methyl-1H-pyrazole-3-sulfonyl chloride (108 mg, 0.597 mmol), 4-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilypethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride (from example 5, step 4; 250 mg, 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 (4 mL) and trifluoroacetic acid (4 mL, 0.05 mol) for 30 min, evaporated under reduced pressure. To the resultant residue was added methanol (5 mL) and ethylenediamine (0.5 mL, 0.007 mol). The resulting 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 (183 mg, 76.6%). LCMS calculated for C22H26N9O2S(M+H)+: m/z=480.2; Found: 480.0. 1H NMR (300 MHz, CD3OD): δ 8.92 (1H, s), 8.86 (1H, s), 8.49 (1H, s), 7.83 (1H, d, J=3.6 Hz), 7.69 (1H, d, J=2.1 Hz), 7.23 (1H, d, J=3.6 Hz), 6.59 (1H, d, J=2.1 Hz), 4.94 (1H, m), 3.89 (3H, s), 3.70 (2H, m), 3.12 (2H, m), 2.33 (2H, m), 2.19 (1H, m), 1.94 (1H, m), 1.82 (1H, m), 1.58 (1H, m), 1.32 (2H, m), 1.05 (1H, m) ppm.

Workup

  1. customSolvents were evaporated
  2. customevaporated under reduced pressure
  3. stirringThe resulting 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-27d199d3a2d24590bcf32c4db5db55bb
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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