What Is Bis(4-tetrahydropyranyl)amine?

Bis(4-tetrahydropyranyl)amine is a secondary amine in which both substituents on the nitrogen atom are tetrahydropyran-4-yl (oxane-4-yl) groups. The tetrahydropyran (THP) ring is a fully saturated six-membered oxygen-containing heterocycle widely recognized in medicinal chemistry for improving aqueous solubility, metabolic stability, and overall drug-likeness compared with purely carbocyclic analogues.

The compound contains a single N–H bond characteristic of secondary amines, enabling it to participate in a broad range of transformations including acylation, sulfonylation, reductive amination, and transition-metal-catalyzed C–N coupling reactions. Its two ring oxygens also provide additional polarity and potential for hydrogen-bond acceptance, features frequently exploited during lead optimization in pharmaceutical research.

Key Properties and Structural Features

The structure of Bis(4-tetrahydropyranyl)amine consists of a central nitrogen flanked symmetrically by two THP rings attached at their 4-position. This symmetric substitution pattern typically results in a well-defined solid or liquid at room temperature with predictable chromatographic behavior. Key structural and physicochemical highlights include:

• Amine nucleophilicity: The secondary amine nitrogen is a competent nucleophile for acyl chlorides, anhydrides, isocyanates, and electrophilic aromatic or aliphatic substrates.
• Polarity and solubility: The two ring oxygens increase the polar surface area relative to dialkyl amines lacking heteroatoms, improving compatibility with protic solvents and aqueous reaction media.
• Conformational rigidity: The THP rings impose moderate conformational constraint, which can be beneficial for structure–activity relationship (SAR) studies.
• Bioisosteric value: The THP group is a recognized bioisostere for tert-butyl and cyclohexyl groups in drug discovery, offering improved metabolic stability.

Note: Specific melting point, boiling point, and exact molecular weight data should be confirmed from the certificate of analysis (CoA) provided with SKU B731737.

Applications in Organic and Medicinal Chemistry

Bis(4-tetrahydropyranyl)amine serves primarily as a nucleophilic amine building block and a nitrogen source in multi-step synthetic sequences. Representative applications include:

1. Amide bond formation: Reaction with activated carboxylic acid derivatives (acid chlorides, active esters, or via coupling reagents such as HATU or EDC) to produce bis-THP amides with improved aqueous solubility.
2. Reductive amination: Condensation with aldehydes or ketones followed by reduction provides tertiary amine products incorporating the bis-THP motif.
3. Buchwald–Hartwig amination: As a secondary amine coupling partner in palladium-catalyzed C–N bond-forming reactions with aryl halides.
4. Urea and carbamate synthesis: Reaction with isocyanates or chloroformates affords urea or carbamate products useful in medicinal chemistry programs.
5. SAR exploration: Introduction of the bis-THP amine fragment into drug candidates to modulate lipophilicity, solubility, and metabolic profile.

These applications make the compound especially attractive in early- to mid-stage pharmaceutical discovery and in the synthesis of reference standards or probe molecules.

Safe Handling, Storage, and Regulatory Notes

As with all secondary amine reagents, appropriate laboratory safety precautions should be observed when working with Bis(4-tetrahydropyranyl)amine:

• Personal protective equipment: Wear nitrile gloves, lab coat, and safety eyewear. Avoid inhalation of dust or vapors.
• Ventilation: Handle in a fume hood, particularly when weighing or dissolving the compound.
• Storage: Store in a tightly sealed container under cool, dry, and well-ventilated conditions, away from strong oxidizers and acids. Specific storage temperature recommendations should be confirmed from the product label and CoA for SKU B731737.
• Disposal: Dispose of waste in accordance with local, national, and institutional regulations for amine-containing chemical waste.
• SDS: Always consult the Safety Data Sheet (SDS) available from Aladdin Scientific prior to use. The SDS contains authoritative hazard classification, first-aid measures, and emergency response information.

Note: Specific GHS hazard classifications and pictograms for this compound should be verified from the current SDS supplied with SKU B731737.

Ordering Bis(4-tetrahydropyranyl)amine from Aladdin Scientific

Bis(4-tetrahydropyranyl)amine is available from Aladdin Scientific under SKU B731737. When placing an order, consider the following:

• Pack sizes: Available pack sizes and pricing are listed on the Aladdin Scientific product page. Contact your regional sales representative or the customer service team for bulk or custom quantity inquiries.
• Purity and specifications: Review the certificate of analysis (CoA) for lot-specific purity data, NMR confirmation, and physical data before use in critical assays.
• Lead time: Standard orders are typically dispatched within normal business processing times; contact Aladdin Scientific customer service for current stock availability and estimated delivery timelines.
• Returns and refunds: Refer to Aladdin Scientific's returns and refund policy for conditions applicable to chemical reagent orders.
• Payment and pricing: Volume discounts and institutional pricing may be available; inquire with the sales team for promotional offers or reward points applicable to your account.

For technical questions about applications or compatibility, the Aladdin Scientific technical support team is available to assist.