Methanol → 4-[4-(methylsulfonyl)piperazin-1-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

HRID 1772766Notes

Reaction equation

HRID 1772766 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].Cl.[N:7]1([CH2:13][CH:14]([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:31]=[CH:30][N:29](COCC[Si](C)(C)C)[C:25]=4[N:26]=[CH:27][N:28]=3)[CH:20]=[N:19]2)[CH2:15][C:16]#[N:17])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.C(N(CC)CC)C.FC(F)(F)C(O)=O.CO.C(N)CN>C(#N)C.C(Cl)Cl>[CH3:1][S:2]([N:10]1[CH2:9][CH2:8][N:7]([CH2:13][CH:14]([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:31]=[CH:30][NH:29][C:25]=4[N:26]=[CH:27][N:28]=3)[CH:20]=[N:19]2)[CH2:15][C:16]#[N:17])[CH2:12][CH2:11]1)(=[O:4])=[O:3]

Participants

9

Reactant 6

HCID 887MethanolHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl 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 509956404-[4-(methylsulfonyl)piperazin-1-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrileYield 27%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (137 mg, 0.00119 mol), 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 (0.5 g, 0.994 mmol) and triethylamine (416 μL, 0.00298 mol) were mixed in acetonitrile (5 mL). The mixture was stirred at RT for 1 h. The completion of the reaction was checked with LC/MS. Solvents were evaporated. The crude product was treated with DCM (1 mL) and trifluoroacetic acid (1 mL, 0.01 mol) for 30 min. The reaction mixture was evaporated under reduced pressure. To the resultant residue was added methanol (3 mL, 0.07 mol) and ethylenediamine (0.3 mL, 0.004 mol) and stirred at RT for 30 min, and concentrated to dryness 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 110 mg (27%) of the desired product. LCMS calculated for C18H23N8O2S(M+H)+: m/z=415.2; Found: 415.0. 1H NMR (400 MHz, CD3OD): δ 8.66 (1H, s), 8.63 (1H, s), 8.37 (1H, s), 7.51 (1H, d, J=3.6 Hz), 6.95 (1H, d, J=4.0 Hz), 4.95 (1H, m), 3.19-3.14 (6H, m), 2.95 (2H, m), 2.77 (3H, s), 2.67 (2H, m), 2.65 (2H, m) ppm.

Workup

  1. customSolvents were evaporated
  2. customThe reaction mixture was evaporated under reduced pressure
  3. stirringstirred at RT for 30 min
  4. concentrationconcentrated to dryness 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-e7b6469406b04736b4a321e8e43a259d
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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