Trifluoroacetic acid → HCID 178496721, compound

HRID 2087058Notes

Reaction equation

HRID 2087058 reaction equation
[NH2:1][CH2:2][CH:3]1[O:7][CH:6]([O:8][CH:9]([CH:49]2[CH:53]([OH:54])[CH:52]([OH:55])[CH:51]([N:56]3[CH:61]=[CH:60][C:59](=[O:62])[NH:58][C:57]3=[O:63])[O:50]2)[CH:10]([C:46]([OH:48])=O)[NH:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:45])[CH:17]([CH:40]([OH:44])[CH:41]([CH3:43])[CH3:42])[NH:18][C:19](=[O:39])[CH:20]([CH:32]2[CH2:37][CH2:36][NH:35][C:34](=[NH:38])[NH:33]2)[NH:21][C:22](=[O:31])[NH:23][CH:24]([CH:28]([CH3:30])[CH3:29])[C:25]([OH:27])=[O:26])[CH:5]([O:64][CH3:65])[CH:4]1[OH:66].CC(=O)CC(=O)C.[F:74][C:75]1[CH:80]=[CH:79][C:78]([N:81]=[C:82]=[O:83])=[CH:77][CH:76]=1.FC(F)(F)C(O)=O>O.CO.O1CCOCC1.N1C=CC=CC=1>[NH2:1][CH2:2][C@H:3]1[O:7][CH:6]([O:8][C@@H:9]([C@@H:49]2[C@@H:53]([OH:54])[C@@H:52]([OH:55])[C@H:51]([N:56]3[CH:61]=[CH:60][C:59](=[O:62])[NH:58][C:57]3=[O:63])[O:50]2)[CH:10]2[N:11]([CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:45])[CH:17]([CH:40]([OH:44])[CH:41]([CH3:42])[CH3:43])[NH:18][C:19](=[O:39])[CH:20]([CH:32]3[CH2:37][CH2:36][NH:35][C:34](=[NH:38])[NH:33]3)[NH:21][C:22](=[O:31])[NH:23][CH:24]([CH:28]([CH3:29])[CH3:30])[C:25]([OH:27])=[O:26])[C:82](=[O:83])[N:81]([C:78]3[CH:79]=[CH:80][C:75]([F:74])=[CH:76][CH:77]=3)[C:46]2=[O:48])[C@H:5]([O:64][CH3:65])[C@H:4]1[OH:66]

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 31261AcetylacetoneHCID 709554-Fluorophenyl isocyanateHCID 17849389816-({[5-(aminomethyl)-4-hydroxy-3-methoxytetrahydro-2-furanyl]oxy}{5-[2,4-dioxo-3,4-dihydro-1 (2H)-pyrimidinyl]-3,4-dihydroxytetrahydro-2-furanyl}methyl)-9-(1-hydroxy-2-methylpropyl)-6-(2-iminohexahydro-4-pyrimidinyl)-2-isopropyl-4,7,10-trioxo-3,5,8,11, 15-pentaazaheptadecane-1,17-dioic acid

Product 1

HCID 178496721HCID 178496721, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 47.3 mg (50 μmol) of 16-({[5-(aminomethyl)-4-hydroxy-3-methoxytetrahydro-2-furanyl]oxy}{5-[2,4-dioxo-3,4-dihydro-1 (2H)-pyrimidinyl]-3,4-dihydroxytetrahydro-2-furanyl}methyl)-9-(1-hydroxy-2-methylpropyl)-6-(2-iminohexahydro-4-pyrimidinyl)-2-isopropyl-4,7,10-trioxo-3,5,8,11, 15-pentaazaheptadecane-1,17-dioic acid λmax nm in water=259) in 2.5 ml of methanol is added 200 μl of pyridine and 200 μl of 2,4-pentanedione at room temperature. The reaction mixture is stirred overnight (the reaction is monitored by mass spectroscopy (MS)). After the reaction is complete, the volatile materials are removed under reduced pressure. N,N-dimethylformamide (DMF) (3 ml) is added to the residue, followed by addition of 13.0 mg (95 μmol) of 4-fluorophenyl isocyanate. The reaction mixture is stirred at room temperature for 50 hours (the reaction was monitored by MS). The volatile materials are removed under reduced pressure to afford a residue to which is added 5 ml of 0.5% trifluoroacetic acid (TFA) in a 1:1 mixture of water and p-dioxane. The mixture is stirred at room temperature for 2 hours. The reaction is monitored by MS and the desired product is identified by liquid chromatography/mass spectrum (LC/MS). After concentration of volatiles to about one ml, 24 mg (44% yield) of the desired product is obtained as a colorless solid using preparative high pressure liquid chromatography (HPLC).

Workup

  1. customthe volatile materials are removed under reduced pressure
  2. additionN,N-dimethylformamide (DMF) (3 ml) is added to the residue
  3. stirringThe reaction mixture is stirred at room temperature for 50 hours (the reaction
  4. customThe volatile materials are removed under reduced pressure
  5. customto afford a residue to which
  6. stirringThe mixture is stirred at room temperature for 2 hours

Sources & evidence

ORD record
ord-d6dfea7549264b269c08fd0750e941d2
Source dataset
uspto-grants-2004_04
Patent number
US06727232B2

Reaction notes

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