Hydrazine → HCID 24900216, compound

HRID 390084Notes

Reaction equation

HRID 390084 reaction equation
O.NN.[NH2:4][C:5]1[C:6]2[N:13](COCC3C=CC=CC=3)[CH:12]=[C:11]([CH2:23][N:24]([CH3:33])[C@H:25]([C@@H:28]([OH:32])[CH2:29][S:30][CH3:31])[CH2:26][OH:27])[C:7]=2[N:8]=[CH:9][N:10]=1.NN>[Pd].C(O)C>[NH2:4][C:5]1[C:6]2[NH:13][CH:12]=[C:11]([CH2:23][N:24]([CH3:33])[C@H:25]([C@@H:28]([OH:32])[CH2:29][S:30][CH3:31])[CH2:26][OH:27])[C:7]=2[N:8]=[CH:9][N:10]=1

Participants

6

Reactant 3

HCID 9321HydrazineHCID 24654Hydrazine hydrate (1:1)HCID 66953642HCID 66953642, compound

Product 1

HCID 24900216HCID 24900216, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolvent

Procedure

Hydrazine hydrate (0.56 ml, 11.6 mmol) was added dropwise to a suspension of (2S,3R)-2-(((4-amino-5-(benzyloxymethyl)-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)(methyl)amino)-4-(methylthio)butane-1,3-diol (50 mg, 116 μmol), palladium black (50 mg, 47.0 μmol) and ethanol (2 ml). Upon complete addition of the hydrazine the palladium went from a fine suspension to a granular form. The reaction was warmed to 60 C at which point TLC analysis indicated the reaction was complete therefore the reaction was cooled to ambient temperature, the palladium black removed by filtration and the filtrate concentrated in vacuo, and the crude residue co-distilled with ethanol and toluene (50 ml, 2:1 v/v). The resulting residue was purified by flash chromatography on silica gel eluting with 20% 7N NH3 in MeOH/DCM to afford (2S,3R)-2-(((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)(methyl)amino)-4-(methylthio)butane-1,3-diol (30 mg, 96 μmol, 83% yield) as a colourless syrup. 1H NMR (CD3OD) δ 8.16 (s, 1H), 7.43 (s, 1H), 4.11 (d, J=13.4 Hz, 1H), 3.86 (m, 3H), 3.73 (dd, J=11.5, 5.0 Hz, 1H), 2.88 (m, 1H), 2.77 (dd, J=13.7, 3.9 Hz, 1H), 2.54 (dd, J=13.6, 7.0 Hz, 1H), 2.43 (s, 3H), 2.07 (s, 3H). 13C NMR (CD3OD) 152.4, 151.0, 147.6, 129.8, 116.1, 115.4, 70.8, 67.2, 60.1, 50.3, 40.2, 38.8, 16.7.

Workup

  1. temperatureThe reaction was warmed to 60 C at which point TLC analysis
  2. customthe palladium black removed by filtration
  3. concentrationthe filtrate concentrated in vacuo
  4. customThe resulting residue was purified by flash chromatography on silica gel eluting with 20% 7N NH3 in MeOH/DCM

Sources & evidence

ORD record
ord-213e452c3af94c8dbf687c51f0e4330a
Source dataset
uspto-grants-2013_02
Patent number
US08383636B2

Reaction notes

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