Ethylenediamine → 4-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

HRID 1772769Notes

Reaction equation

HRID 1772769 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[N:3]1.Cl.[N:12]1([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])[CH2:17][CH2:16][NH:15][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:15]2[CH2:14][CH2:13][N:12]([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])[CH2:17][CH2:16]2)(=[O:9])=[O:8])=[N:3]1

Participants

9

Reactant 5

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 134744661-Methyl-1H-pyrazole-3-sulfonyl 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 581808954-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrileYield 90.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

1-Methyl-1H-pyrazole-3-sulfonyl chloride (130 mg, 0.72 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; 300 mg, 0.6 mmol), and triethylamine (250 μL, 0.0018 mol) were dissolved in acetonitrile (3 mL). The mixture was stirred at RT for 1 h, and evaporated to dryness under reduced pressure. The residue was treated with DCM (0.5 mL) and trifluoroacetic acid (0.5 mL, 0.006 mol) for 30 min. The reaction mixture was evaporated under reduced pressure. To the resultant residue was added methanol (2 mL) and ethylenediamine (0.2 mL, 0.003 mol). The reaction mixture was stirred at RT for 30 min, and evaporated under reduced pressure. The crude product 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 (259 mg, 90.4%). LCMS calculated for C21H25N10O2S(M+H)+: m/z=481.2; Found: 481.0. 1H NMR (300 MHz, CD3OD): δ 8.95 (1H, s), 8.90 (1H, s), 8.52 (1H, s), 7.88 (1H, d, J=3.6 Hz), 7.71 (1H, d, J=2.4 Hz), 7.27 (1H, d, J=3.6 Hz), 6.62 (1H, d, J=2.4 Hz), 5.15 (1H, m), 3.89 (3H, s), 3.20˜3.12 (8H, m), 2.94 (2H, m), 2.77 (2H, m) ppm.

Workup

  1. customevaporated to dryness under reduced pressure
  2. customThe reaction mixture was evaporated under reduced pressure
  3. stirringThe reaction mixture was stirred at RT for 30 min
  4. customevaporated under reduced pressure
  5. customThe crude product 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-cf4fe88359f948fa99fc39980bc59cbb
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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