951382-34-6

Basic information

• Product Name: L-Proline compd. with (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol (1:1)
• Synonyms: L-Proline compd. with (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol (1:1);l-prolinecompd
• CAS NO: 951382-34-6
• Molecular Formula: C₅H₉NO₂*C₂₁H₂₁FO₅S
• Molecular Weight: 519.5823032
• Mol File: 951382-34-6.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• CAS DataBase Reference: L-Proline compd. with (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol (1:1)(CAS DataBase Reference)
• NIST Chemistry Reference: L-Proline compd. with (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol (1:1)(951382-34-6)
• EPA Substance Registry System: L-Proline compd. with (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol (1:1)(951382-34-6)

Safety Data

• Hazardous Substances Data: 951382-34-6(Hazardous Substances Data)

Usage

General Description

L-Proline compd. with (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol (1:1) is a chemical compound that consists of L-proline and (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol in a 1:1 ratio. L-Proline is an amino acid that is important for the synthesis of collagen and other proteins, while (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol is a synthetic compound with potential antidiabetic and antineoplastic activities. When combined, this compound could potentially exhibit a combination of the individual properties of L-proline and (1S)-1,5-anhydro-1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-D-glucitol, with potential applications in medicine and biotechnology.

Synthetic route

(2S,3R,4R,5S,6R)-2-(3-(benzo[b]thiophen-2-ylmethyl)-4-fluorophenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (761423-87-4) + L-proline (147-85-3) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
In dichloromethane at 35℃; for 3h;	99%
In ethanol; water at 100℃; for 0.5h;	83.7%
In ethanol at 100℃; for 0.5h;

2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide (81058-27-7) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; dibutyl ether / 3 h / -20 °C 1.2: 1 h / 0 °C 1.3: 3 h / 100 °C 2.1: sodium methylate; methanol / 3 h / 65 °C 3.1: ethanol; water / 0.5 h / 100 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; hexane; dibutyl ether / 3.33 h / -20 °C / Inert atmosphere 1.2: 1.33 h / 0 °C / Inert atmosphere 1.3: 3 h / 100 °C / Inert atmosphere 2.1: sodium methylate; methanol / 3 h / 65 °C 3.1: ethanol; water / 0.5 h / 100 °C View Scheme

(2R,3R,4S,5R,6R)-2-chloro-6-(pivaloyloxymethyl)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; dibutyl ether / 3 h / -20 °C 1.2: 1 h / 0 °C 1.3: 3 h / 100 °C 2.1: sodium methylate; methanol / 3 h / 65 °C 3.1: ethanol; water / 0.5 h / 100 °C View Scheme

2-[(5-iodo-2-fluorophenyl)methyl]-1-benzothiophene → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; dibutyl ether / 3 h / -20 °C 1.2: 1 h / 0 °C 1.3: 3 h / 100 °C 2.1: sodium methylate; methanol / 3 h / 65 °C 3.1: ethanol; water / 0.5 h / 100 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; hexane; dibutyl ether / 3.33 h / -20 °C / Inert atmosphere 1.2: 1.33 h / 0 °C / Inert atmosphere 1.3: 3 h / 100 °C / Inert atmosphere 2.1: sodium methylate; methanol / 3 h / 65 °C 3.1: ethanol; water / 0.5 h / 100 °C View Scheme

2-[(5-bromo-2-fluorophenyl)methyl]-1-benzothiophene (1034305-17-3) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; dibutyl ether / 3 h / -20 °C 1.2: 1 h / 0 °C 1.3: 3 h / 100 °C 2.1: sodium methylate; methanol / 3 h / 65 °C 3.1: ethanol; water / 0.5 h / 100 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 1.2: 2 h / 20 - 90 °C 2.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 3.1: dichloromethane / 3 h / 35 °C View Scheme

(1S)-1,5-anhydro-1-{3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl}-2,3,4,6-tetra-O-pivaloyl-D-glucitol → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium methylate; methanol / 3 h / 65 °C 2: ethanol; water / 0.5 h / 100 °C View Scheme

α-D-glucopyranose peracetylate (604-68-2) → Ipragliflozin L-proline (951382-34-6)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: hydrogen bromide; acetic acid / dichloromethane / 0.67 h / 0 °C 2.1: Acidic conditions 3.1: iron(II) sulfate / methanol / 12 h 4.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 4.2: 2 h / 20 - 90 °C 5.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 6.1: dichloromethane / 3 h / 35 °C View Scheme

2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (572-09-8) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: Acidic conditions 2.1: iron(II) sulfate / methanol / 12 h 3.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 3.2: 2 h / 20 - 90 °C 4.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 5.1: dichloromethane / 3 h / 35 °C View Scheme

Benzo[b]thiophene (95-15-8) → Ipragliflozin L-proline (951382-34-6)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran / 1.5 h / -78 °C 1.2: 2 h / -78 °C 2.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane / 0.5 h / -20 °C 3.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 3.2: 2 h / 20 - 90 °C 4.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 5.1: dichloromethane / 3 h / 35 °C View Scheme

5-bromo-2-fluorobenzaldehyde (93777-26-5) → Ipragliflozin L-proline (951382-34-6)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran / 1.5 h / -78 °C 1.2: 2 h / -78 °C 2.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane / 0.5 h / -20 °C 3.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 3.2: 2 h / 20 - 90 °C 4.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 5.1: dichloromethane / 3 h / 35 °C View Scheme

1-bromo-α-D-glucopyranose (61403-85-8) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: iron(II) sulfate / methanol / 12 h 2.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 2.2: 2 h / 20 - 90 °C 3.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 4.1: dichloromethane / 3 h / 35 °C View Scheme

2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl bromide (4196-35-4) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 1.2: 2 h / 20 - 90 °C 2.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 3.1: dichloromethane / 3 h / 35 °C View Scheme

(1-benzothiophen-2-yl)(5-bromo-2-fluorophenyl)methanol (1034305-11-7) → Ipragliflozin L-proline (951382-34-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane / 0.5 h / -20 °C 2.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 2.2: 2 h / 20 - 90 °C 3.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 4.1: dichloromethane / 3 h / 35 °C View Scheme

alpha-D-glucopyranose (492-62-6) → Ipragliflozin L-proline (951382-34-6)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium acetate / 0.17 h / 140 °C 2.1: hydrogen bromide; acetic acid / dichloromethane / 0.67 h / 0 °C 3.1: Acidic conditions 4.1: iron(II) sulfate / methanol / 12 h 5.1: n-butyllithium / dibutyl ether; toluene; n-heptane / 2 h / -40 °C / Inert atmosphere 5.2: 2 h / 20 - 90 °C 6.1: pentamethylbenzene,; boron trichloride / dichloromethane / 4 h / -78 °C 7.1: dichloromethane / 3 h / 35 °C View Scheme

Upstream product

• 604-68-2 α-D-glucopyranose peracetylate 
• 572-09-8 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 
• 95-15-8 Benzo[b]thiophene 
• 93777-26-5 5-bromo-2-fluorobenzaldehyde 
• 61403-85-8 1-bromo-α-D-glucopyranose 
• 4196-35-4 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl bromide 
• 1034305-11-7 (1-benzothiophen-2-yl)(5-bromo-2-fluorophenyl)methanol 
• 492-62-6 alpha-D-glucopyranose 
• 1034305-17-3 2-[(5-bromo-2-fluorophenyl)methyl]-1-benzothiophene 
• 81058-27-7 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide 
• 761423-87-4 (2S,3R,4R,5S,6R)-2-(3-(benzo[b]thiophen-2-ylmethyl)-4-fluorophenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol 
• 147-85-3 L-proline 

Relevant articles and documents

Method for synthesizing ipragliflozin

The invention discloses a method for synthesizing ipragliflozin. The method comprises the following steps: (1) generating alkylation reaction by formula-4 compound and formula-5 compound to generate aformula-6 compound; (2) carrying out deprotection on the formula-6 compound to generate a formula-7 compound, i.e., ipragliflozin. Compared with the prior art, the preparation method disclosed by theinvention is characterized in that adopted starting raw materials are cheap and can be easily obtained, a synthesis route is short, operation is convenient, cost is lower and general yield is high. The method conforms to the concept of green chemistry and is suitable for industrial production. (The formulas are shown in the description.).

COCRYSTAL OF C-GLYCOSIDE DERIVATIVE AND L-PROLINE

A cocrystal of (1S)-1,5-anhydro-1-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-D-glucitol and L-proline. It is a cocrystal of known compound A, which has a constant quality, is superior in storage stability, has no moisture absorptivity, and is suitable as a crystal of a drug substance used for preparing pharmaceuticals.