L-Proline → HCID 53672916, compound

HRID 1607099Notes

Reaction equation

[C:1]1([C:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[NH:8][CH2:9][CH2:10][S:11][C:12]([O:14]C2C=CC([N+]([O-])=O)=CC=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:36]1[CH2:43][CH2:42][CH2:41][C@H:37]1[C:38]([OH:40])=[O:39]>>[C:24]1([C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[NH:8][CH2:9][CH2:10][S:11][C:12]([N:36]2[CH2:43][CH2:42][CH2:41][C@H:37]2[C:38]([OH:40])=[O:39])=[O:14])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

Reactant 2

HCID 145742L-Proline

HCID 15616513HCID 15616513, compound

Product 1

HCID 53672916HCID 53672916, compoundYield 50%

Procedure

N-triphenylmethyl-2-paranitrophenoxycarbonylthioethylamine (1.0 g) and L-proline (713 mg) were subjected to a similar reaction described in Reference 2 to give N-triphenylmethyl-2-[(S)-2-carboxypyrrolidino)carbonylthioethylamine (475 mg) which was then dissolved in a mixture of anhydrous dimethylformamide (1.5 ml) and anhydrous acetonitrile (4 ml). After addition of dicyclohexylcarbodiimide (256 mg) and 4-aminohenol (256 mg), the reaction solution was stirred at room temperature for 5 hours and was then concentrated under reduced pressure. The concentrated solution was dissolved in chloroform (50 ml), followed by washing in turns with an aqueous solution of 10% citric acid, a saturated sodium bicarbonate solution, water and a saturated solution of sodium chloride. The chloroform layer was dried by use of anhydrous sodium sulfate and was then concentrated under reduced pressure. The residual substance was purified by silica gel column chromatography using a solvent system of chloroform/methanol (20:1 v/v) to obtain N-triphenylmethyl-2-[(S)-2-(4-hydroxyphenyl)aminocarbonylpyrrolidino]carbonylthioethylamine (0.45 g: yield 79.0%). From the product triphenylmethyl was removed in a similar manner to that described in Example 4 to produce 2-(S)-2-4-hydroxyphenyl)aminocarbonylpyrrolidino]carbonylthioethylamine (crude formate: 445 mg). This product was dissolved in anhydrous methanol (7 ml). To the reaction solution were added triethylamine (873 μl) and mitomycin A (380 mg: 0.87 molar equivalent). The mixture was treated in a similar manner to that described in Example 1 to obtain Compound 45 (160 mg) in the form of grayish blue powders with a yield of 39%.

Sources & evidence

ORD record: ord-42761becea604397a80b8485dca13ed3
Source dataset: uspto-grants-1989_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04863935

Reaction notes

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