Claims
- 1. A process for introducing the aminomethyl moiety (CH.sub.2 NH.sub.2) onto the furan ring of a psoralen or furocoumarin ring structure, said psoralen or furocoumarin ring structure being unsubstituted or substituted with a lower alkyl group at the C-4 position, said process consisting of:
- (1) reacting under anhydrous conditions, a mixture of a psoralen or furocoumarin and an aminomethylating agent selected from the group consisting of N-hydroxymethylphthalimide, N-hydroxymethylbenzamide, N-hydroxymethylacetamide, and N-N'-dimethyl-N-hydroxymethylurea suspended or dissolved in an anhydrous polar solvent with a strong protonic acid, Lewis acid or mixture of such acids, and
- (2) separating the aminomethylated psoralen or furocoumarin by hydrazine cleavage in hydrazine hydrate and ethanol to produce a 4' or 5' aminomethyl psoralen or furocoumarin.
- 2. The process of claim 1 wherein said lower alkyl substituted psoralen is selected from the group consisting of 4,5',8-trimethylpsoralen; 4,4',8-trimethylpsoralen; 4',8-dimethyl-8-ethylpsoralen; 4'-ethyl-4,8-dimethylpsoralen; 5',8-dimethylpsoralen; 4,5'-dimethyl-8-n-propylpsoralen, 4',8-dimethyl-4-m-psopylpsoralen; 4,5'-dimethylpsoralen; and 4-methyl-8-n-propylpsoralen.
- 3. The process of claim 1 wherein said anhydrous polar solvent is selected from the group consisting of chloroform, methylene chloride, acetic acid and formic acid.
- 4. The process of claim 1 wherein said protonic or Lewis acid is selected from the group consisting of trifluoroacetic acid, methane sulfonic acid, trifluoromethane sulfonic acid, boron trifluoride etherate and fuming sulfuric acid.
- 5. The process of claim 1 wherein Step (1) of the reaction sequence is carried out in the temperature range of about 10.degree.-22.degree. C.
- 6. The process of claim 1 wherein the relative quantity of said aminomethylating agent is no more than about 20-45% greater than said psoralen.
- 7. A process for introducing the aminomethyl moiety (--CH.sub.2 NH.sub.2) onto psoralen which consist of:
- (1) reacting, under anhydrous conditions, a mixture of 4,4',8-trimethylpsoralen and N-hydroxymethylphthalimide suspended in methylene chloride treated to dropwise addition of trifluoromethanesulfonic acid dissolved in trifluoroacetic acid, and
- (2) cleaving the resulting 5'-N-phthalimidomethyl-4,4',8-trimethylpsoralen in hydrazine hydrate and 95% ethanol to yield 5'-aminomethyl-4,4',8-trimethylpsoralen.
- 8. A process for introducing the aminomethyl moiety (--CH.sub.2 NH.sub.2) onto psoralen which consist of:
- (1) reacting, under anhydrous conditions, a mixture of 4,5',8-trimethylpsoralen and N-hydroxymethylphthalimide suspended in methylene chloride treated to dropwise addition of trifluoromethane sulfonic acid and trifluoroacetic acid, and
- (2) cleaving the resulting 4'-N-phthalimidomethyl-4,5',8-trimethylpsoralen in hydrazine hydrate and 95% ethanol to yield 4'-aminomethyl-4,5',8-trimethylpsoralen.
- 9. A process for introducing the aminomethyl moiety (--CH.sub.2 NH.sub.2) onto psoralen which consist of:
- (1) reacting, under anhydrous conditions, a mixture of 4,4'-dimethylpsoralen and N-hydroxymethylphthalimide suspended in methylene chloride treated to dropwise addition of trifluoromethanesulfonic acid and trifluoroacetic acid, and
- (2) cleaving the resulting 5'-N-phthalimidomethyl-4,4'-dimethylpsoralen in hydrazine hydrate and 95% ethanol to yield 5'-aminomethyl-4,4'-dimethylpsoralen.
- 10. A process for introducing the aminomethyl moiety (--CH.sub.2 NH.sub.2) onto psoralen which consist of:
- (1) reacting, under anhydrous conditions, a mixture of 4'-methylpsoralen and N-hydroxymethylphthalimide suspended in methylene chloride treated to dropwise addition of trifluoromethanesulfonic acid and trifluoroacetic acid, and
- (2) cleaving the resulting 5'-N-phthalimidomethyl-4'-methylpsoralen in hydrazine hydrate and 95% ethanol to yield 5'-aminomethyl-4'-methylpsoralen.
Parent Case Info
This is a continuation of co-pending application Ser. No. 07/065,077, filed on June 16, 1987, now abandoned and which is a continuation of application Ser. No. 06/706,831, filed 2/28/85 now abandoned.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
4124598 |
Hearst et al. |
Nov 1978 |
|
4294822 |
Kaufman |
Oct 1981 |
|
4465842 |
Desbois et al. |
Aug 1984 |
|
Continuations (2)
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Number |
Date |
Country |
Parent |
65077 |
Jun 1987 |
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Parent |
706831 |
Feb 1985 |
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