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

HRID 2063367Notes

Reaction equation

HRID 2063367 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-56b97a0cc7d04ff1bd7d799d07329977
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

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