Triethylamine → HCID 24995241, compound

HRID 1684890Notes

Reaction equation

HRID 1684890 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]([C@@H:8]2[O:16][C@H:15]3[C@@H:10]([O:11][P:12]([NH:18][C@@H:19]([CH2:25][CH3:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21])(=[O:17])[O:13][CH2:14]3)[C@:9]2([OH:28])[CH3:27])[C:4](=[O:29])[N:3]=1.CCN(CC)CC.[CH2:37]([CH:40]([CH2:44][CH2:45][CH3:46])[C:41](Cl)=[O:42])[CH2:38][CH3:39]>C1COCC1.CN(C=O)C.CN(C1C=CN=CC=1)C>[OH:28][C@:9]1([CH3:27])[C@@H:10]2[O:11][P:12]([NH:18][C@@H:19]([CH2:25][CH3:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21])(=[O:17])[O:13][CH2:14][C@H:15]2[O:16][C@H:8]1[N:5]1[CH:6]=[CH:7][C:2]([NH:1][C:41](=[O:42])[CH:40]([CH2:44][CH2:45][CH3:46])[CH2:37][CH2:38][CH3:39])=[N:3][C:4]1=[O:29]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 762402-Propylvaleryl chlorideHCID 24994610HCID 24994610, compound

Product 1

HCID 24995241HCID 24995241, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl (2S)-2-{[(4aR,6R,7R,7aR)-6-(4-amino-2-oxopyrimidin-1(2H)-yl)-7-hydroxy-7-methyl-2-oxidotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-yl]amino}butanoate, prepared according the procedure described for Example 6, was diluted with a solution THF:DMF (5:2, 0.03 M). Et3N (4.0 eq.) and DMAP (0.2 eq.) were added then the mixture was cooled to 0° C. and 2-propylpentanoyl chloride (2.5 eq.) was added drop-wise. The mixture was immediately warmed to room temperature and stirred for 2 hours. The reaction was quenched by the addition of 1N HCl (aq) to bring the pH to 6, and then the solvent was removed in vacuum. The crude was purified by RP-HPLC (stationary phase: column Symmetry C18, 7 μm, 19×300 mm. Mobile phase: acetonitrile/H2O buffered with 0.1% TFA) to afford the title compound as white powder (36%).

Workup

  1. temperatureThe mixture was immediately warmed to room temperature
  2. customThe reaction was quenched by the addition of 1N HCl (aq)
  3. customthe solvent was removed in vacuum
  4. customThe crude was purified by RP-HPLC (stationary phase: column Symmetry C18, 7 μm, 19×300 mm. Mobile phase: acetonitrile/H2O buffered with 0.1% TFA)

Sources & evidence

ORD record
ord-bc6a452f3f224c378d3826ebd986f44b
Source dataset
uspto-grants-2012_04
Patent number
US08148349B2

Reaction notes

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