Morpholine → HCID 44829125, compound

HRID 1475127Notes

Reaction equation

HRID 1475127 reaction equation
[P:1]([O:5][CH2:6][C@H:7]1[O:11][C@@H:10]([N:12]2[CH:19]=[C:18]([I:20])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[C@H:9]([OH:21])[C@@H:8]1[OH:22])([OH:4])([OH:3])=O.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.N1C=CC=CC=1SSC1C=CC=CN=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CS(C)=O.CN(C=O)C>[CH2:24]1[N:23]([P:1]([O:5][CH2:6][C@H:7]2[O:11][C@@H:10]([N:12]3[C:13](=[O:14])[NH:15][C:16](=[O:17])[C:18]([I:20])=[CH:19]3)[C@H:9]([OH:21])[C@@H:8]2[OH:22])([OH:3])=[O:4])[CH2:28][CH2:27][O:26][CH2:25]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11776TriphenylphosphineHCID 650932,2'-Dipyridyl disulfideHCID 44829127HCID 44829127, compound

Product 1

HCID 44829125HCID 44829125, compoundYield 104.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6228DimethylformamideSolvent

Procedure

5-Iodouridine-5′-monophosphate 1 (292 mg, 0.65 mmol) was dissolved in dry DMSO, co-evaporated (3×) with dry DMF, and finally dissolved in 0.5 mL of dry DMSO. Morpholine (400 μL, 4.6 mmol) was added and the reaction mixture was stirred at room temperature for 5 min. Dipyridyl disulfide (500 mg, 2.3 mmol) and triphenylphosphine (600 mg, 2.3 mmol) were added in 5 min intervals, and the reaction mixture was stirred for another 60 minutes at room temperature. Upon quenching of the reaction with 0.1 M NaI in acetone a precipitate formed. The supernatant was removed, and the precipitate was washed repeatedly with cold acetone, to give 354 mg (99% yield) of 5-Iodouridine-5′-phosphoromorpholidate as a white powder. This material was used in the next step without further purification. δH (400 MHz, D2O) 3.04-3.16 (4H, m, H-Morpholine), 3.65-3.73 (4H, m, H-Morpholine), 4.00-4.15 (2H, m, H-5′), 4.24-4.26 (1H, m, H-4′), 4.27-4.32 (1H, m, H-3′), 4.36 (1H, t, J=5.4 Hz, H-2′), 5.94 (1H, d, J=5.8 Hz, H-1′), 8.17 (1H, s, H-6). δC (75.5 MHz, D2O) 64.3 (morpholine), 63.3 (d, J=5.4 Hz, C-5′), 66.3 (morpholine), 67.8 (C-5), 68.6 (C-3′), 73.2 (C-2′), 83.0 (d, J=8.4 Hz, C-4′), 88.2 (C-1′), 145.0 (C-6), 153.3 (C-2), 161.9 (C-4); OP (121.5 MHz, D2O) 11.0 ppm. m/z (ESI) 519.9968 [M+H]+, C13H19IN3O9P requires 519.9976.

Workup

  1. stirringthe reaction mixture was stirred for another 60 minutes at room temperature
  2. customUpon quenching of the reaction with 0.1 M NaI in acetone a precipitate
  3. customformed
  4. customThe supernatant was removed
  5. washthe precipitate was washed repeatedly with cold acetone

Sources & evidence

ORD record
ord-f20479686e18449fa70386ad5e829495
Source dataset
uspto-grants-2015_04
Patent number
US09018370B2

Reaction notes

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