Triethylamine → 4-[1-(1-methyl-2-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}ethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

HRID 1772789Notes

Reaction equation

HRID 1772789 reaction equation
[CH3:1][CH:2]([N:10]1[CH:14]=[C:13]([C:15]2[C:16]3[CH:23]=[CH:22][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:17]=3[N:18]=[CH:19][N:20]=2)[CH:12]=[N:11]1)[CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.C(N(CC)CC)C.[CH3:39][N:40]1[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[N:41]1>ClCCl>[CH3:1][CH:2]([N:10]1[CH:14]=[C:13]([C:15]2[C:16]3[CH:23]=[CH:22][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:17]=3[N:18]=[CH:19][N:20]=2)[CH:12]=[N:11]1)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([S:45]([C:42]2[CH:43]=[CH:44][N:40]([CH3:39])[N:41]=2)(=[O:47])=[O:46])[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 134744661-Methyl-1H-pyrazole-3-sulfonyl chlorideHCID 670549204-[1-(1-methyl-2-piperazin-1-ylethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 670549524-[1-(1-methyl-2-{4-[(1-methyl-1H-pyrazol-3-yl)sulfonyl]piperazin-1-yl}ethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidineYield 87.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-[1-(1-methyl-2-piperazin-1-ylethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (1.1 g, 2.5 mmol) in dichloromethane (20 mL) was added triethylamine (0.52 mL, 3.7 mmol) followed by 1-methyl-1H-pyrazole-3-sulfonyl chloride (0.54 g, 3.0 mmol). The reaction was stirred at RT for 1 h, then quenched with saturated sodium bicarbonate, and extracted with dichloromethane. The combined organic layers were washed with brine and dried over sodium sulfate. After being concentrated to dryness, the residue was purified on silica gel, eluting with 0 to 10% methanol in dichloromethane to provide the product (1.28 g, 87.7%). LCMS calculated for C26H40N9O3SSi (M+H)+: m/z=586.3; Found: 586.2. The product was separated on a ChiralCel OD-H column (3×25 cm, 5 μM), eluting with a gradient of ethanol in hexanes at flow rate 28 mL/min, to give the two enantiomers. First peak with retention time 20.76 min and second peak with retention time 24.72 min.

Workup

  1. customquenched with saturated sodium bicarbonate
  2. extractionextracted with dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationAfter being concentrated to dryness
  6. customthe residue was purified on silica gel
  7. washeluting with 0 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-1eb17faf4aa741e8bdaeeac800ddae51
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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