Picolinic acid → HCID 86737468, compound

HRID 1413104Notes

Reaction equation

HRID 1413104 reaction equation
[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([OH:30])[CH2:24][C:22](=[O:23])[N:21]([CH3:31])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:32])=[CH:9][CH:8]=[CH:7][CH:6]([O:33][CH3:34])[C:5]2([OH:39])[NH:35][C:36]([O:38][CH:3]1[CH2:4]2)=[O:37].[N:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1C(O)=O.C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.ClCCl>[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([OH:30])[CH2:24][C:22](=[O:23])[N:21]([CH3:31])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:32])=[CH:9][CH:8]=[CH:7][CH:6]([O:33][CH3:34])[C:5]2([OH:39])[NH:35][C:36]([O:38][CH:3]1[CH2:4]2)=[O:37].[N:40]1[CH:41]=[CH:42][CH:43]=[C:44]([C:36]([O-:38])=[O:37])[CH:45]=1

Participants

6

Reactant 3

HCID 1018Picolinic acidHCID 10868DicyclohexylcarbodiimideHCID 5358230HCID 5358230, compound

Product 1

HCID 86737468HCID 86737468, compoundYield 68.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

As in Example 8, maytansinol (109.0 mg, 0.193 mmol), picolic acid (144.2 mg, 1.171 mmols), DCC (278.5 mg, 1.352 mmols) and DMAP (50.2 mg, 0.411 mmol) are reacted in 10 ml of dry dichloromethane at room temperature for 6 hours. After the insolubles are filtered off, the filtrate is concentrated to dryness and the residue is dissolved in ethyl acetate, washed with water and dried over anhydrous sodium sulfate. The solvent is then distilled off. The residue is chromatographed on a column of silica gel (80 g) and elution is carried out with H2O-saturated ethyl acetate, the eluate being collected in 16-g fractions. Fractions 24 through 49 are pooled and the solvent is distilled off to recover 98 mg of crude product. This crude product is chromatographed again on a column of silica gel (50 g), elution being carried out with chloroform-methanol (40:1, V/V). Fraction 18 through 33 (16 g each) are pooled, the solvent distilled off and the residue dissolved in ethyl acetate, followed by addition of ether. The resultant crystals are collected by filtration. By the above procedure is obtained 45.4 mg of maytansinol 3-picolinate. m.p. 190°-193° C. (decompn.)

Workup

  1. filtrationAfter the insolubles are filtered off
  2. concentrationthe filtrate is concentrated to dryness
  3. dissolutionthe residue is dissolved in ethyl acetate
  4. washwashed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent is then distilled off
  7. customThe residue is chromatographed on a column of silica gel (80 g) and elution
  8. customthe eluate being collected in 16-g fractions
  9. distillationthe solvent is distilled off
  10. customto recover 98 mg of crude product
  11. customThis crude product is chromatographed again on a column of silica gel (50 g), elution
  12. distillationthe solvent distilled off
  13. dissolutionthe residue dissolved in ethyl acetate
  14. additionfollowed by addition of ether
  15. filtrationThe resultant crystals are collected by filtration

Sources & evidence

ORD record
ord-d9ad207573f441ec98f77b7ec0449a2b
Source dataset
uspto-grants-1981_02
Patent number
US04248870

Reaction notes

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