Hydrochloric Acid → 4-(morpholin-4-yl)-5-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

HRID 1750283Notes

Reaction equation

HRID 1750283 reaction equation
[N:1]1([C:7]2[C:8]3[C:15]([C:16]4[CH:17]=[N:18][N:19](C5CCCCO5)[CH:20]=4)=[CH:14][N:13]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:9]=3[N:10]=[CH:11][N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>ClCCl.O1CCOCC1>[N:1]1([C:7]2[C:8]3[C:15]([C:16]4[CH:20]=[N:19][NH:18][CH:17]=4)=[CH:14][N:13]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:9]=3[N:10]=[CH:11][N:12]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 867069564-(morpholin-4-yl)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 867069574-(morpholin-4-yl)-5-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-(morpholin-4-yl)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (C19) (4.0 g, 8.2 mmol) in dichloromethane (20 mL) was added a solution of hydrogen chloride in 1,4-dioxane (4 M, 100 mL). The reaction mixture was stirred at room temperature for 2 hours, then poured into a mixture of ethyl acetate (300 mL) and saturated aqueous sodium bicarbonate solution (300 mL). The aqueous layer was extracted with ethyl acetate (2×300 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (Gradient: 10% to 80% ethyl acetate in petroleum ether) afforded the product as a yellow oil. Yield: 2.18 g, 5.44 mmol, 66%. LCMS m/z 401.3 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.78 (s, 2H), 7.19 (s, 1H), 5.64 (s, 2H), 3.56-3.66 (m, 6H), 3.34-3.40 (m, 4H), 0.91-0.98 (m, 2H), −0.03 (s, 9H).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (2×300 mL)
  2. washthe combined organic layers were washed with saturated aqueous sodium chloride solution (100 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification via silica gel chromatography (Gradient: 10% to 80% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-288885d15cd14ff69c23471f4b91255f
Source dataset
uspto-grants-2015_10
Patent number
US09156845B2

Reaction notes

Loading…