Ninhydrin → Tacrolimus

HRID 1991027Notes

Reaction equation

HRID 1991027 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].C(Cl)CCl.Cl.ON1C2C=CC=CC=2N=N1.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>CN(C=O)C>[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

6

Reactant 4

HCID 10236NinhydrinHCID 757711-HydroxybenzotriazoleHCID 22619321HCID 22619321, compoundHCID 72524391HCID 72524391, compound

Product 1

HCID 445643Tacrolimus

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the 17-allyl-1,14-dihydroxy-12-{2-[4-(7-carboxy-heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraone prepared in Reference Production Example 2 (38.4 mg, 0.04 mmol), TOYO-Pearl resin (TSKgel AF-amino, 100 μl, free amino group (available amino group) 0.01 mmol), EDC/HCl (9.2 mg, 0.048 mol), 1-hydroxybenzotriazole (HOBt; 6.5 mg, 0.048 mmol) and DMF (1 ml) was stirred at room temperature for 6 hours. The reaction end point was confirmed as the time when no residual amino group became visually observable by the ninhydrin reaction. The reaction rate at this time was calculated to be about 82%. After confirmation of completion of the reaction, the resin was washed with DMF five times. Acetic anhydride (100 μl) and DMF (400 μl) were added thereto, and this was followed by stirring at room temperature for 1 hour. Subsequently, the resin was thoroughly washed with DMF, and the TOYO-Pearl resin with FK506 obtained was used as the control affinity resin in the binding experiments described below.

Workup

  1. customAfter confirmation of completion of the reaction
  2. washthe resin was washed with DMF five times
  3. additionAcetic anhydride (100 μl) and DMF (400 μl) were added
  4. stirringby stirring at room temperature for 1 hour
  5. washSubsequently, the resin was thoroughly washed with DMF

Sources & evidence

ORD record
ord-54a22424150f48e69847b7301763220b
Source dataset
uspto-grants-2010_01
Patent number
US07645614B2

Reaction notes

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