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(Diethylamino)sulfur trifluoride → (S)-4-(2-chloro-8-(3-fluorooxetan-3-yl)-9-methyl-9H-pur-in-6-yl)-3-methylmorpholine

HRID 2063367
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2063367
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:12]3(O)[CH2:15][O:14][CH2:13]3)[N:8]2[CH3:11])=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]2[CH3:23])[N:3]=1.C(N(S(F)(F)[F:30])CC)C>C(Cl)Cl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:12]3([F:30])[CH2:15][O:14][CH2:13]3)[N:8]2[CH3:11])=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]2[CH3:23])[N:3]=1
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Komponenten

4

Edukt 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 58222531(S)-3-(2-chloro-9-methyl-6-(3-methylmorpholino)-9H-purin-8-yl)oxetan-3-ol

Produkt 1

HCID 58222529(S)-4-(2-chloro-8-(3-fluorooxetan-3-yl)-9-methyl-9H-pur-in-6-yl)-3-methylmorpholineAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of (S)-3-(2-chloro-9-methyl-6-(3-methylmorpholino)-9H-purin-8-yl)oxetan-3-ol (127.6 mg, 0.364 mmol) in anhydrous DCM (8.0 mL) at −78° C. under N2 was added diethylaminosulfur trifluoride (59.5 μL, 0.436 mmol, 1.2 eq.). The reaction mixture was warmed to 0° C. over 3 h, stirred at RT for 2 h, and quenched with 1N sodium hydroxide solution. The reaction mixture was diluted with ethyl acetate. The two phases were separated, and the organic layer was washed with water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in hexane) to give the product as a foam (79.6 mg, 62.0%). 1H NMR (CDCl3, 500 MHz) δ ppm 6.10 to 4.40 (broad s, 2H), 5.30 to 5.19 (m, 2H), 5.10 (dd, J=20.7, 7.8 Hz, 2H), 4.04 to 3.98 (m, 1H), 3.83 to 3.73 (m, 2H), 3.68 (d, J=1.5 Hz, 3H), 3.61 (td, J=11.6, 2.8 Hz, 1H), 3.48 (broad s, 1H), 1.40 (d, J=6.8 Hz, 3H); LC-MS m/z (method A)=342 [M+H]+, RT=2.36 min.

Aufarbeitung

  1. customquenched with 1N sodium hydroxide solution
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. customThe two phases were separated
  4. washthe organic layer was washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-56b97a0cc7d04ff1bd7d799d07329977
Quelldatensatz
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08288381B2

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