Water → HCID 58180872, compound

HRID 1772773Notes

Reaction equation

HRID 1772773 reaction equation
[CH:1]1([S:4](Cl)(=[O:6])=[O:5])[CH2:3][CH2:2]1.Cl.[NH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH:16]([N:20]2[CH:24]=[C:23]([C:25]3[C:26]4[CH:33]=[CH:32][N:31](COCC[Si](C)(C)C)[C:27]=4[N:28]=[CH:29][N:30]=3)[CH:22]=[N:21]2)[CH2:17][C:18]#[N:19])[CH2:11][CH2:10]1.C(N(CC)CC)C.O>C(#N)C>[CH:1]1([S:4]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][CH:16]([N:20]3[CH:24]=[C:23]([C:25]4[C:26]5[CH:33]=[CH:32][NH:31][C:27]=5[N:28]=[CH:29][N:30]=4)[CH:22]=[N:21]3)[CH2:17][C:18]#[N:19])[CH2:11][CH2:10]2)(=[O:6])=[O:5])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 2760919Cyclopropanesulfonyl chlorideHCID 67054933HCID 67054933, compound

Product 1

HCID 58180872HCID 58180872, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Cyclopropanesulfonyl chloride (77.0 mg, 0.548 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 (250 mg, 0.498 mmol), and triethylamine (208 μL, 0.00149 mol) were dissolved in acetonitrile (1.0 mL). The mixture was stirred at RT for 1 h, water was added to make a homogeneous solution and purified with preparative LCMS (pH=10) to provide the desired product. The product 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 resulting residue was added methanol (5 mL) and ethylenediamine (0.5 mL, 0.007 mol) and the resultant mixture was stirred at RT for 30 min. The reaction mixture was 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 (185 mg, 84.5%). LCMS calculated for C21H26N7O2S(M+H)+: m/z=440.2; Found: 440.0. 1H NMR (300 MHz, CD3OD): δ 8.98 (1H, s), 8.88 (1H, s), 8.53 (1H, s), 7.85 (1H, d, J=3.6 Hz), 7.28 (1H, d, J=3.6 Hz), 4.98 (1H, m), 3.68 (2H, m), 3.15 (2H, m), 2.73 (2H, m), 2.37 (1H, m), 2.23 (1H, m), 1.98 (1H, m), 1.87 (1H, m), 1.62 (1H, m), 1.29 (3H, m), 0.97 (4H, m) ppm.

Workup

  1. custompurified with preparative LCMS (pH=10)

Sources & evidence

ORD record
ord-390f32c7b8f9482d8a5e4517a517cfbb
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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