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Structure of 13725-38-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 13725-38-7 |
Formula : | C5H11NO |
M.W : | 101.15 |
SMILES Code : | NC1CCC(O)C1 |
MDL No. : | MFCD14705160 |
InChI Key : | YHFYRVZIONNYSM-UHFFFAOYSA-N |
Pubchem ID : | 14299310 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P301+P330+P331-P303+P361+P353-P363-P304+P340-P310-P321-P260-P264-P280-P305+P351+P338-P405-P501 |
Class: | 8 |
UN#: | 3259 |
Packing Group: | Ⅲ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1 For preparation of 3-cis-hydroxycyclopentylamine, see EP-A-322242. 4-(3,4-trans-dihydroxycyclopentyl)amino-5,6-diinethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine.1 1H NMR (200 MHz, CDCl3) delta-1.92-1.99 (br, 2H), 2.14 (s, 3H), 2.20 (br, 2H), 2.30 (s, 3H), 2.41-2.52 (br, 2H), 4.35 (m, 2H), 4.98 (m, 2H), 7.38-7.47 (m, 3H), 8.38-8.42 (m, 2H), 9.53 (s, 1H); MS (ES): 339.2 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 23 Preparation of (Z/E)-3-aminocyclopentanol 10 g of 1-nitro-3-O-acetyl-4-cyclopentene was hydrogenated in acetic acid over 1 g of 10% Pd/C at 1000 lb H2 50 overnight. After filtration and evaporation a crude oily residue of 18 g was obtained. This residue was hydrolyzed in 75 ml 3n NaOH at 85-100 for one hour. Cooling, followed by extraction with n-butanol yielded 7.4 g of crude 1,3-aminobutanol. The product was further purified via column chromatography over silica gel. The mass spectrum of the viscous material showed the molecular ion at m/e 101 and the ir spectrum showed strong absorptions in the NH and OH region at 3200-3400 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; | Step 1: synthesis of tert-butyl (3-hydroxycyclopentyl)carbamate A mixture of <strong>[13725-38-7]3-aminocyclopentanol</strong> (1.0 g, 7.3 mmol), Boc2O (2.0 g, 9.25 mmol) and TEA (3.0 g, 30. 0 mmol) in DCM (25 mL) was stuffed at RT overnight. The resulting mixture was thenconcentrated in vacuo. The residue was purified by silica-gel chromatography (EA:PE= 1:4 to1:1) to afford tert-butyl (3-hydroxycyclopentyl)carbamate as a yellow gum.A mixture of <strong>[13725-38-7]3-aminocyclopentanol</strong> (1.0 g, 7.3 mmol), Boc2O (2.0 g, 9.25 mmol) and TEA (3.0 g, 30. 0 mmol) in DCM (25 mL) was stuffed at RT overnight. The resulting mixture was thenconcentrated in vacuo. The residue was purified by silica-gel chromatography (EA:PE= 1:4 to1:1) to afford tert-butyl (3-hydroxycyclopentyl)carbamate as a yellow gum. | |
With triethylamine; In dichloromethane; at 20℃; | Step 1: synthesis of tert-butyl(3-hydroxycyclopentyl)carbamate A mixture of <strong>[13725-38-7]3-aminocyclopentanol</strong> (1.0 g, 7.3 mmol), Boc2O (2.0 g, 9.25 mmol) and TEA (3.0 g, 30.0 mmol) in DCM (25 mL) was stirred at RT overnight. The resulting mixture was then concentrated in vacuo. The residue was purified by silica-gel chromatography (EA:PE=1:4 to 1:1) to afford tert-butyl(3-hydroxycyclopentyl)carbamate as a yellow gum. | |
With trifluoroacetic acid; In dichloromethane; at 20℃; | A mixture of <strong>[13725-38-7]3-aminocyclopentanol</strong> (1.0 g, 7.3 mmol), Boc2O (2.0 g, 9.25 mmol) and TEA (3.0 g, 30.0 mmol) in DCM (25 mL) was stirred at RT overnight. The resulting mixture was then concentrated in vacuo. The residue was purified by silica-gel chromatography (EA:PE=1:4 to 1:1) to afford tert-butyl (3-hydroxycyclopentyl)carbamate as a yellow gum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 3.0h; | Compound 145 Synthesis following procedure S4 with <strong>[13725-38-7]3-aminocyclopentanol</strong> as amine, after completion, the reaction mixture was directly loaded on a silica gel column for purification, using a heptane to EtOAc gradient yielding compound 145 as a 83 (145a, 145b): 17 (145c, 145d) mixture of diastereomers. Method F; Rt: 0.82 and 0.86 min. m/z: 410.2 (M+NH4)+ Exact mass: 392.1. Compound 145 was separated in it's isomers by preparative SFC (Stationary phase: Chiralpak Diacel AD 30 x 250 mm), Mobile phase: C02, MeOH with 0.4% iPrNH2), the desired fractions were collected, evaporated, dissolved in MeOH and evaporated again yielding compound 145a (238 mg) and 145b (236 mg) and a mixture of compound 145c and 145d. The mixture of 145c and 145d was further purified by Preparative SFC (Stationary phase: Chiralpak Diacel AD 30 x 250 mm), Mobile phase: C02, EtOH with 0.4% iPrNH2), the desired fractions were collected, evaporated, dissolved in MeOH and evaporated again yielding 145c (29 mg) and 145d (27 mg). 145a and 145b: N-(4-fluoro-3-methyl-phenyl)-3- [[(li?,35)-3-hydroxycyclopentyl]sulfamoyl]benzamide or N-(4-fluoro-3-methyl- phenyl)-3 - [ [( 1 S,3R)-3 -hydroxy cyclopentyl] sulfamoyl]benzamide . Method F; Rt: 0.85 min. m/z: 410.2 (M+NH4)+ Exact mass: 392.1. 1H NMR (400 MHz, DMSO- g) delta ppm 1.21 (ddd, J=13.3, 7.8, 6.1 Hz, 1 H), 1.36 - 1.64 (m, 4 H), 1.84 - 1.95 (m, 1 H), 2.25 (d, J=l . l Hz, 3 H), 3.37 - 3.47 (m, 1 H), 3.85 - 3.96 (m, 1 H), 4.25-5.00 (1H, br. s), 7.14 (t, J=9.2 Hz, 1 H), 7.35-7.75 (1H, br. s), 7.54 - 7.63 (m, 1 H), 7.68 (dd, J=7.0, 2.2 Hz, 1 H), 7.75 (t, J=7.8 Hz, 1 H), 8.01 (d, J=7.9 Hz, 1 H), 8.19 (d, J=7.7 Hz, 1 H), 8.36 (s, 1 H), 10.46 (br. s., 1 H) 145c and 145d: N-(4-fluoro-3-methyl-phenyl)-3-[[(15',35)-3-hydroxycyclopentyl]- sulfamoyl]benzamide or N-(4-fluoro-3-methyl-phenyl)-3-[[(li?,3i?)-3-hydroxycyclo- pentyl]sulfamoyl]benzamide. Method F; Rt: 0.82 min. m/z: 410.2 (M+NH4) Exact mass: 392.1. 1H NMR (400 MHz, DMSO-d6 ) delta ppm 1.17 - 1.35 (m, 2 H), 1.41 (ddd, J=13.4, 8.0, 5.7 Hz, 1 H), 1.56 (ddd, J=13.2, 7.3, 2.6 Hz, 1 H), 1.69 - 1.83 (m, 2 H), 2.25 (d, J=1.8 Hz, 3 H), 3.59 - 3.72 (m, 1 H), 3.99 - 4.09 (m, 1 H), 4.43 (d, J=3.5 Hz, 1 H), 7.14 (t, J=9.2 Hz, 1 H), 7.55 - 7.63 (m, 1 H), 7.68 (dd, J=7.0, 2.2 Hz, 1 H), 7.73 - 7.84 (m, 2 H), 7.96 - 8.02 (m, 1 H), 8.20 (dt, J=7.9, 1.2 Hz, 1 H), 8.36 (t, J=1.7 Hz, 1 H), 10.48 (br. s., 1 H) 145a: [a] : +5.2 (c 0.56 w/v %, DMF); 145b: [a] : -5.4 (c 0.60 w/v %, DMF); 145c: [a] : -3.5 (c 0.46 w/v %, DMF); 145d: [a] : +2.5 (c 0.44 w/v %, DMF) Procedure S4: 3-[(4-fluoro-3-methyl-phenyl)carbamoyl]benzenesulfonyl chloride (250 mg, 0.76 mmol) and DIPEA (329 mu, 1.9 mmol, 2.5 eq) dissolved in CH2C12 (5 mL) were added to a tube containing an amine (1.1 eq). The reaction mixture was stirred for 3 hours. 1M HC1 (5 mL) was added. Workup W4: The organic layer was separated and loaded on a silica gel column. The mixture was purified using gradient elution from heptane to EtOAc. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In 1,4-dioxane; dichloromethane; at 0℃; for 1.0h; | solution of tert-butyl (3-hydroxycyclopentyl)carbamate (1.6 g, 1 equiv.) in DCM (2 mL) was cooled to 0 C. Next, 4 M HC1 in dioxane (6 mL) was added to the reaction mixture and stirred for 1 h. Dioxane was removed under vacuum to give 3-aminocyclopentanol hydrochloride. ?HNMR 400 MHz, DMSO-d6: oe 8.02-8.19 (m, 1H), 4.12-4.23 (m, 2H), 3.43-3.58 (m, 1H),2.04-2.10 (m, 1H), 1.88-1.94 (m, 2H), 1.66-1.75 (m, 2H), 1.49-1.60 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26.9 mg | To a solution of 5-cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopentapyrimidin-4-yl]-benzoic acid (intermediate 6)(50.0 mg, 0.08 mmol) in N,N-dimethylformamide (2.0 mL) triethylamine (32.1 muL, 0.23 mmol) is added and the reaction mixture is stirred at room temperature. After 5 min N,N,N?,N?-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (24.7 mg, 0.08 mmol) is added and the vi reaction is stirred at room temperature for 5 min. Then 3-amino-cyclopentanole (10.6 mg, 0.08 mmol) is added and stirring is continued at room temperature overnight. The reaction mixture is purified by reversed phase. Yield: 26.9 mg; ESI mass spectrum [M+H]+=539; Retention time HPLC: 0.73 min (method 003_CA04). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 120 - 130℃; for 44.0h; | (3S)-Oxolan-3-amine hydrochloride (83 mg, 0.67 mmol) was added at room temperature to a stirred suspension of 8 -bromo- 1 -(3 ,4-dichlorob enzyl)-3 , 7-dimethyl- 1H- purine-2,6(3H,71])-dione (70 mg, 0.17 mmol) and DIEA (233 pi, 1.34 mmol) in nBuOH (5 ml). The resulting mixture was heated at 120C and stirred for 20h. Further (3S)-oxolan-3- amine hydrochloride (83 mg, 0.67 mmol) and DIEA (233 pi, 1.34 mmol) were added. The temperature was increased to 130C and stirring was continued. After 24h the solvent was removed in vacuo and the residue was purified by prep-HPLC to obtain the title compound. The title compounds were synthesized in a similar fashion as described in Procedure 7B using 1 -(benzo[b]thiophen-5-ylmethyl)-8-bromo-3 ,7-dimethyl-3 ,7-dihydro- 1H- purine-2,6-dione and <strong>[13725-38-7]3-aminocyclopentan-1-ol</strong>. The c/s and trans diastereomers were separated by flash chromatography. (±)- 1 -(1 -benzothiophen-5-ylmethyl)-8-{ [(cis)-3hydroxycyclopentyl]amino} -3 ,7-dimethyl-2,3 ,6,7-tetrahydro- 1H-purine-2,6-dione or (±)- 1- (1 -benzothiophen-5 -ylmethyl)-8- { [(trans)-3 -hydroxycyclopentyl] amino } -3, 7-dimethyl- 2,3,6,7-tetrahydro-1H-purine-2,6-dione; ?H NIVIR (500 IVIHz, CDC13) 7.94 (d, J = 1.3 Hz, 1H), 7.79 (d, J= 8.3 Hz, 1H), 7.51 (dd, J= 8.3, 1.6 Hz, 1H), 7.38 (d, J 5.4 Hz, 1H), 7.28 (dd, J 5.4, 0.5 Hz, 1H), 5.29 (s, 2H), 4.58 - 4.41 (m, 2H), 3.97 (d, J= 6.7 Hz, 1H), 3.66 (s, 3H), 3.51 (s, 3H), 2.40 (td, J= 13.9, 7.8 Hz, 1H), 2.29 -2.18 (m, 1H), 2.18 -2.06 (m, 1H),1.80- 1.63 (m, 2H), 1.52 - 1.45 (m, 1H); ESI: m/z 426.1 (M+H)t Example 75: (±)- 1 -(1 -benzothiophen-5-ylmethyl)-8-{ [(cis)-3 -hydroxycyclopentyl]amino} -3 ,7-dimethyl-2,3 ,6,7-tetrahydro- 1H-purine-2,6-dione or (±)- 1- (1 -benzothiophen-5 -ylmethyl)-8- { [(trans)-3 -hydroxycyclopentyl] amino } -3, 7-dimethyl- 2,3,6,7-tetrahydro-1H-purine-2,6-dione; ?H NIVIR (500 IVIHz, CDC13) 7.94 (d, J = 1.3 Hz, 1H), 7.79 (d, J= 8.3 Hz, 1H), 7.51 (dd, J= 8.3, 1.5 Hz, 1H), 7.38 (d, J 5.4 Hz, 1H), 7.29 (d, J 5.4 Hz, 1H), 5.29 (s, 2H), 5.04 (d, J 8.5 Hz, 1H), 4.54 -4.43 (m, 1H), 4.43 -4.34 (m, 1H), 3.63 (s, 3H), 3.51 (s, 3H), 2.67 (d, J= 3.8 Hz, 1H), 2.16- 1.94 (m, 3H), 1.93 - 1.79 (m, 3H); ESI: m/z 426.0 (M+H)t |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In tetrahydrofuran; at 80℃; for 4.0h; | (0554) To a solution of compound Int-2j (1.0 g, 3.06 mmol) in THF (15 mL) was added <strong>[13725-38-7]3-aminocyclopentanol</strong> (0.927 g, 9.17 mmol) and AcOH (0.3 mL). The mixture was stirred at 80 C. for 4 h. The solvent was removed under vacuum, the residue was purified by a silica gel column eluting with 5% MeOH/dichloromethane to afford compound Int-29a. MS (M+H)+: 379.1 |
A187952 [1184919-69-4]
3-Aminocyclopentanol hydrochloride
Reason: Free-salt