1160295-21-5

Basic information

• Product Name: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester hydrochloride
• Synonyms: MLN-4924 hydrochloride;Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester hydrochloride;MLN4924 (HCl salt);MLN4924 HCl
• CAS NO: 1160295-21-5
• Molecular Formula: C₂₁H₂₅N₅O₄S*ClH
• Molecular Weight: 479.98024
• EINECS: 200-258-5
• Mol File: 1160295-21-5.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester hydrochloride(1160295-21-5)
• EPA Substance Registry System: Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester hydrochloride(1160295-21-5)

Safety Data

• Hazardous Substances Data: 1160295-21-5(Hazardous Substances Data)

Usage

General Description

Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester hydrochloride is a chemical compound that is a hydrochloride salt form of a methyl ester of a cyclopentyl derivative. It is a potential inhibitor of protein kinase C (PKC) that may have a role in cancer therapy. This complex compound consists of various molecular structures including an indenyl group, a pyrrolopyrimidine ring, and a hydroxycyclopentyl group, all combined with a sulfamic acid moiety. Its molecular formula is C26H30ClN5O3S.

Synthetic route

(1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-(hydroxymethyl)-cyclopentanol (905580-90-7) + (1,4-diazabicyclo[2.2.2]octan-1-ium-1-ylsulfonyl)(tert-butoxycarbonyl)amide (1375958-75-0) → ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)-methyl sulfamate hydrochloride (1160295-21-5)

Conditions	Yield
Stage #1: (1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-(hydroxymethyl)-cyclopentanol; (1,4-diazabicyclo[2.2.2]octan-1-ium-1-ylsulfonyl)(tert-butoxycarbonyl)amide In acetonitrile at 55℃; for 8h; Stage #2: With hydrogenchloride In water; acetonitrile at 20℃; for 2h;	42%

((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)-methyl sulfamate → ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)-methyl sulfamate hydrochloride (1160295-21-5)

Conditions	Yield
With hydrogenchloride In ethanol at 50℃; Product distribution / selectivity; Reflux;

C20H20O5 → ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)-methyl sulfamate hydrochloride (1160295-21-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: di-tert-butyl-diazodicarboxylate; phosphorous acid trimethyl ester / toluene / 3 h / 12 °C 2.1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 24 h / 25 °C 3.1: hydrogenchloride; water / tetrahydrofuran / 4.5 h / 40 °C 4.1: acetonitrile / 8 h / 55 °C 4.2: 2 h / 20 °C View Scheme

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)-methyl sulfamate hydrochloride (1160295-21-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: di-tert-butyl-diazodicarboxylate; phosphorous acid trimethyl ester / toluene / 3 h / 12 °C 2.1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 24 h / 25 °C 3.1: hydrogenchloride; water / tetrahydrofuran / 4.5 h / 40 °C 4.1: acetonitrile / 8 h / 55 °C 4.2: 2 h / 20 °C View Scheme

C26H22ClN3O4 → ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)-methyl sulfamate hydrochloride (1160295-21-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 24 h / 25 °C 2.1: hydrogenchloride; water / tetrahydrofuran / 4.5 h / 40 °C 3.1: acetonitrile / 8 h / 55 °C 3.2: 2 h / 20 °C View Scheme

Upstream product

• 905580-90-7 (1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-(hydroxymethyl)-cyclopentanol 
• 1375958-75-0 (1,4-diazabicyclo[2.2.2]octan-1-ium-1-ylsulfonyl)(tert-butoxycarbonyl)amide 
• 3680-69-1 4-chloro-1H-pyrrolo[2,3-d]pyrimidine 
• 905579-51-3 ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)-methyl sulfamate 

Relevant articles and documents

Tumor inhibitor MLN4924 synthetic method (by machine translation)

The invention discloses tumor inhibitor MLN4924 synthetic method, which belongs to the field of chemical synthesis, the method to compound A and compound E as the starting material, by mitsunobu reaction, amination reaction, deprotected base and sulphur esterification four-step reaction can synthesize the target product MLN4924, has the advantage of short synthetic route, and the raw material source is wide, low cost, mild reaction conditions, the operation is safe, friendly to the environment, high yield, can be up to 40% more than, is suitable for industrial large-scale production. (by machine translation)