Ninhydrin → Tacrolimus

HRID 1991024Notes

Reaction equation

HRID 1991024 reaction equation
[CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:65])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51]C(=O)CCCCCCC(O)=O)[CH:47]([O:63][CH3:64])[CH2:46]2)[CH:8]([CH3:66])[CH:7]([OH:67])[CH2:6][C:5]1=[O:68])[CH:2]=[CH2:3].CCN=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O.C(OC(=O)C)(=O)C.CN(C)C=O>C(Cl)Cl.CN1CCCC1=O.C1C=CC=CC=1>[CH3:32][C@H:27]1[CH2:28][C:29]([CH3:31])=[CH:30][C@@H:4]([CH2:1][CH:2]=[CH2:3])[C:5](=[O:68])[CH2:6][C@H:7]([OH:67])[C@@H:8]([CH3:66])[C@@H:9](/[C:43](/[CH3:65])=[CH:44]/[C@H:45]2[CH2:46][C@@H:47]([O:63][CH3:64])[C@H:48]([OH:51])[CH2:49][CH2:50]2)[O:10][C:11](=[O:42])[C@H:12]2[N:17]([CH2:16][CH2:15][CH2:14][CH2:13]2)[C:18](=[O:41])[C:19](=[O:40])[C@:20]2([OH:39])[O:35][C@@H:24]([C@@H:23]([O:36][CH3:37])[CH2:22][C@H:21]2[CH3:38])[C@@H:25]([O:33][CH3:34])[CH2:26]1

Participants

8

Reactant 5

HCID 10236NinhydrinHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 72524391HCID 72524391, compoundHCID 86761394acetic anhydride DMF

Product 1

HCID 445643Tacrolimus

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 19383075dichloromethane N-methyl-2-pyrrolidoneSolvent

Procedure

The syrup obtained in Example 1 was centrifuged with benzene and concentrated under reduced pressure, and dissolved in a mixed solvent of methylene chloride/N-methyl-2-pyrrolidone (4/1) (0.3 ml), and WSC (1.44 mg, 7.5 μmol) and 1-hydroxybenzotriazole (1.01 mg, 7.5 μmol) were added. This solution was added to 10 μl of TOYO-Pearl resin (TSKgel AF-amino; 0.01 mmol amine is present in 100 μl) and shaken at room temperature overnight. After completion of the reaction, the resin was thoroughly washed with a mixed solvent of methylene chloride/N-methyl-2-pyrrolidone (4/1), and DMF, and the percent condensation yield was determined by the ninhydrin test (about 29%). A mixed solution of acetic anhydride/DMF (1/4) (0.3 ml) was added to the resin obtained, and this was followed by shaking at room temperature for 30 minutes. After completion of the reaction, the resin was thoroughly washed with methylene chloride, dimethylformamide (DMF) and 20% aqueous ethanol, and this resin was used as the affinity resin in the subsequent experiments.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionwere added
  3. customAfter completion of the reaction
  4. washthe resin was thoroughly washed with a mixed solvent of methylene chloride/N-methyl-2-pyrrolidone (4/1), and DMF
  5. customthe percent condensation
  6. customyield
  7. customobtained
  8. stirringby shaking at room temperature for 30 minutes
  9. customAfter completion of the reaction
  10. washthe resin was thoroughly washed with methylene chloride, dimethylformamide (DMF) and 20% aqueous ethanol

Sources & evidence

ORD record
ord-667291f776064bb6b6d0d90a4de81add
Source dataset
uspto-grants-2010_01
Patent number
US07645614B2

Reaction notes

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