Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 136030-00-7 | MDL No. : | MFCD00216656 |
Formula : | C9H11NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 149.19 | Pubchem ID : | - |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.33 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 42.94 |
TPSA : | 46.25 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.05 cm/s |
Log Po/w (iLOGP) : | 1.58 |
Log Po/w (XLOGP3) : | 0.23 |
Log Po/w (WLOGP) : | 0.28 |
Log Po/w (MLOGP) : | 0.87 |
Log Po/w (SILICOS-IT) : | 1.04 |
Consensus Log Po/w : | 0.8 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.31 |
Solubility : | 7.25 mg/ml ; 0.0486 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.76 |
Solubility : | 25.9 mg/ml ; 0.173 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.81 |
Solubility : | 2.29 mg/ml ; 0.0154 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.08 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
26.5 % ee | at 60℃; | Crude (S) -3-cyclohexane-1-carboxylic acid / (1R, 2S) -1-amino-3-cyclohexane-1-carboxylic acid (4.55 g), (1R, 2S) -1-amino-2-indanol (4.30 g) was added to water containing 2-propanol (45 mL), heated to 60 ° C. To dissolve the precipitate. The reaction solution was cooled to 50 ° C. and stirred for 2 hours after crystallization. It was gradually cooled to room temperature at 5 ° C / h and stirred for 12 hours. The precipitate was collected by filtration, washed with 2-propanol (10 mL), and dried under reduced pressure at 40 ° C. to obtain the title compound (5.05 g, 50.9percent, 26.5percent ee) as a white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | at 0 - 20℃; for 96 h; | A 3 L round bottom flask was charged with diethyl MALONIMIDATE dihydrochloride (25.8 g, 0.112 moles, 1.0 equiv. ) and DIMETHYLFORMAMIDE (DMF) (320 mL). The mixture was cooled in an ice bath. To this suspension was added (LR, 2S)- (+)-CIS-L-AMINO-2- indanol (40 G, 0.268 moles, 2.4 equivalents), in portions, over twenty minutes. The ice bath then was removed, and the reaction allowed to warm to room temperature, during which time the reaction product precipitated from the reaction. After four days stirring at room temperature, the reaction was filtered. The collected white solid was suspended in CH2Cl2 (450 ML). The mixture then was washed with water (260 ML) and brine (260 mL). The organic lay- er was dried over sodium sulfate (NA2SO4), filtered, and concentrated to an off-white solid. Drying overnight under vacuum provided 23.9 g (65percent yield) of the bis (oxazoline) (4). 1H NMR (300 MHZ/CDCL3) : 6 7. 45 (m, 2H, Ar-H); 7.27-7. 21 (m, 6H, AR-H) ; 5.56 (d, J=7.9 Hz, 2H, N-CH); 5.34 (M, 2H, O-CH) ; 3.39 (DD, J=7.0, 18. 0 Hz, 2H, Ar-CHH); 3 : 26 (S, 2H, -CH2-0); 3.16 (d, J=18.0 Hz, 2H, 14-CHH). The'NMR is consistent with the peak assignments made in WO 00/15599. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium carbonate In tetrahydrofuran; water; ethyl acetate at 20℃; | |
With dmap; triethylamine In dichloromethane at 23℃; Yield given; | ||
With triethylamine In tetrahydrofuran; water at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium carbonate In tetrahydrofuran; water; ethyl acetate at 20℃; | |
88.5% | With dmap; triethylamine In dichloromethane at 23℃; for 12h; | |
With dmap; triethylamine In dichloromethane at 23℃; Yield given; |
With triethylamine In tetrahydrofuran; water at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With hydrogen In ethanol for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In dichloromethane for 48h; | |
60% | In N,N-dimethyl-formamide at 23℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With hydrogen In tetrahydrofuran; methanol for 4h; Ambient temperature; Title compound not separated from byproducts; | |
With hydrogen In tetrahydrofuran; methanol for 4h; Ambient temperature; Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In dichloromethane at 20℃; for 5h; | 41.a Example 41; [(1S,2S,4R)-2-Hydroxy-4-(4-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]-amino}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentyl]methyl sulfamate (Compound I-52); Step a: tert-Butyl [(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamate; (1R,2S)-1-Aminoindan-2-ol (1.83 g, 12.3 mmol) was dissolved in DCM (70.0 mL) and TEA (3.42 mL, 24.5 mmol) was added. Di-tert-butyldicarbonate (2.81 g, 12.9 mmol) was added at rt and the reaction mixture was stirred for 5 h. The solution was concentrated in vacuo and purified via silica gel chromatography eluting with a gradient of 0 to 100% EtOAc in hexanes to afford the title compound (3.12 g, 100%). LC/MS: Rt=1.55 min, ES+ 250. (AA standard). |
100% | With Sodium hydrogenocarbonate In tetrahydrofuran; lithium hydroxide monohydrate at 20℃; for 18h; Inert atmosphere; | |
100% | With triethylamine In dichloromethane for 5h; | 12.a (1R,2S)-1-Aminoindan-2-ol (1.83 g, 12.3 mmol) was dissolved in DCM (70.0 mL) and TEA (3.42 mL, 24.5 mmol) was added. Di-tert-butyldicarbonate (2.81 g, 12.9 mmol) was added and the reaction mixture was stirred for 5 h. The solution was concentrated in vacuo and purified via silica gel chromatography eluting with a gradient of 0 to 100% EtOAc in hexanes to afford the title compound (3.12 g, 100%). LC/MS: Rt=1.55 min, ES+ 250. (AA standard). |
99% | With triethylamine In tetrahydrofuran | |
99% | With triethylamine In tetrahydrofuran at 0 - 20℃; | 31.A To a solution of (lR, 2S)-l-amino-indan-2-ol (5.04 g, 33. 8 mmol) in THF (50 mL) cooled at 0°C were sequentially added triethylamine (5.65 MOL, 40. 6 mmol) and (Boc) 20 (7. 37 G, 33. 8 MMOL). The reaction mixture was stirred overnight at room temperature, quenched with H2O, and extracted with EtOAc (3 x 50 mL). The organic extracts were combined, washed with water and brine, and dried (MGSO4). Removal of the solvent gave the (1R, 2S)-(2-hydroyx-indan-1-yl)-carbamic acid tert- butyl ester (8.39 g, 99%) as a white solid, which was taken to the next step without purification. MS M/Z 250 [(M+H) +J. |
99% | With triethylamine In tetrahydrofuran at 0 - 20℃; | 8.A Part A ; To a solution of (1R, 2S)-L-AMINO-INDAN-2-OL (5.04 g, 33.8 mmol) in THF (50 mL) cooled at 0°C was added triethylamine (5.65 mL, 40.6 mmol) and (BOC) 20 (7.37 g, 33.8 mmol) sequentially. The reaction mixture was stirred overnight at room temperature, quenched with H2O, and extracted with EtOAc (3 x 50 mL). The organic extracts were combined, washed with water, brine, and dried (MgSO4). Removal of the solvent gave the desired product (1R, 2S)- (2-HYDROXY- INDAN-L-YL)-CARBAMIC acid tert-butyl ester (8.39 g, 99%) as a white solid that was taken to the next step without purification. |
98% | In methanol at 20℃; | 7.1.1. (1R,2S)-1-(tertio-Butyloxycarbonylamino)indan-2-ol ((-)-7b) To a solution of (+)-7a (400 mg, 2.68 mmol) in MeOH (10 mL) was added Boc2O (662 mg, 3.0 mmol, 1.1 equiv). After 3-5 h stirring at room temperature, the solvent was evaporated and the residue (0.9 g) recrystallised in cyclohexane to give pure (-)-7b (634 mg, 98%) as colorless crystals, mp = 77-79 °C [lit.24 for the (1S,2R)-enantiomer, mp 76.1-76.8 °C], inlMMLBox = -13 (c 1, CHCl3). 1H and 13C NMR (CDCl3) data were identical with those reported in the lit.24 |
96% | With triethylamine In dichloromethane; ethyl acetate at 20℃; for 20h; | 41 Method #41 (1R,2S)-1-[(1,1-dimethylethoxy)carbonylamino]-2 hydroxyindan (1R,2S)-1-Amino-2-hydroxyindan (10.0 g, 67.1 mmol) was dissolved in dichloromethane (550 ml) and triethylamine (18.7 ml, 134.2 mmol). Di-tert-butyl dicarbonate (18.3 g, 83,9 mmol) in dichloromethane (50 ml) was added and the mixture stirred at room temperature for 20 hours then evaporated.ethyl acetate (200 ml) was added, the solution washed with water, dried over magnesium sulphate and evaporated.The crude product was purified by chromatography on silica with 4:1 iso-hexane:ethyl acetate as eluent to give the title compound as a white solid (16.1 g, 96%); NMR 1.42 (9H, s), 2.78 (1H, dd), 3.0 (1H, dd), 4.3-4.42 (1H, m), 4.78-4.9 (1H, m), 4.9-5.0 (1H, m), 6.3 (1H, d), 7.0-7.25 (4H, m). |
96% | With triethylamine In dichloromethane at 20℃; for 20h; | (LR, 2S)-1-AMINO-2, 3-dihydro-lH-inden-2-ol (CAS Reg. No. 136030-00-7; 10 g, 67.1 mmol) was dissolved in DCM (550 mL) and Et3N (18.7 mL, 134.2 MMOL). Di-tert-butyl dicarbonate (18.3 g, 83.9 mmol) in DCM (50 mL) was added and the mixture stirred at ambient temperature for 20 hours, anf then evaporated. EtOAc (200 mL) was added, the solution washed with water (200 mL), dried (MGS04) and the volatiles removed under reduced pressure. The crude product was purified by flash column chromatography (SI02, 4: 1, iso- hexane: EtOAc eluent) to provide the title compound (16.1 g, 96%) as a white solid. 'H NMR 8 : 1.42 (m, 9H), 2.78 (dd, 1H), 3.00 (dd, 1H), 4.36 (m, 1H), 4.84 (m, 1H), 4.95 (m, 1H), 6.3 (d, 1H), 7.13 (m, 4H). |
96% | With triethylamine In dichloromethane at 18 - 25℃; for 20h; | 9 (1R, 2S)-1-Amino-2, 3-DIHYDRO-LH-INDEN-2-OL (CAS Reg. No. 136030-00-7; 10 g, 67.1 mmol) was dissolved in DCM (550 mL) and triethylamine (18.7 mL, 134.2 mmol). Di-tert-butyl dicarbonate (18.3 g, 83.9 mmol) in DCM (50 mL) was added and the mixture stirred at ambient temperature for 20 hours, and then evaporated. EtOAc (200 mL) was added, the solution washed with water (200 ML), dried (MGS04) and the volatiles removed under reduced pressure. The crude product was purified by flash column chromatography (SI02, 4: 1, iso-hexane : EtOAc eluent) to provide the title compound (16.1 g, 96%) as a white solid. H NMR 8 : 1.42 (m, 9H), 2.78 (dd, 1H), 3.00 (dd, 1H), 4.36 (m, 1H), 4.84 (m, 1H), 4.95 (m, 1H), 6.3 (d, 1H), 7.13 (m, 4H). |
96% | Stage #1: (1R,2S)-(+)-cis-1-amino-2-indanol With triethylamine In dichloromethane at 0℃; for 0.333333h; Inert atmosphere; Stage #2: di-<i>tert</i>-butyl dicarbonate In dichloromethane at 0℃; Inert atmosphere; | |
92% | With anhydrous sodium carbonate In tetrahydrofuran; lithium hydroxide monohydrate at 0 - 20℃; for 3h; | 61.1 Step 1. tert-butyl ((lR,2S)-2-hydroxy-2,3- dihydro-lH-inden-l-yl)carbamate. Step 1. tert-butyl ((lR,2S)-2-hydroxy-2,3- dihydro-lH-inden-l-yl)carbamate. To a stirring uspension of (1R, 2S)-(+)-cis-amino-2- indanol (115 mg, 0.77 mmol) and sodium carbonate (183 mg, 1.72 mmol) in THF (2.9 mL) and water (1.3 mL) was added a solution of di-tert-butyl dicarbonate (190 mg, 0.88 mmol) in THF (0.7 mL) and stirred at 0 °C for lh, then rt for 2h. The reaction mixture was diluted with water (50 mL), extracted with EtOAc (3 x 50 mL), and the combined organic phase was washed with brine and dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography using 25% EtOAc/Hexanes eluent to afford tert-butyl ((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)carbamate as a white solid (117 mg, 92%). NMR (500MHz, CDC ) δ ppm 7.11 - 7.25 (m, 5H), 5.32 - 5.44 (m, 1H), 4.85 - 5.00 (m, 1H), 4.35 - 4.50 (m, 1H), 3.31 (bs, 1H), 2.99 (dd, J= 16.4, 4.6 Hz, 1H), 2.82 (dd, J= 10.3, 8.8 Hz, 1H), 1.47 (s, 9H). |
90% | With triethylamine In dichloromethane at 20℃; for 20h; | Intermediate 8: (1R, 2S)-L-[(L. L-DIMETHVLETHOXV) CARBONVLAMINOL-2 HVDROXVINDAN (1R, 2S)-1-Amino-2-hydroxyindan (12. 0g, 80. 5MMOL) was dissolved in DCM (500 ml) and triethylamine (22.4 ml, 161MMOL). Di-tert-butyl dicarbonate (22. 0g, 100MMOL) in DCM (50 ml) was added and the mixture stirred at room temperature for 20 hours then evaporated. EtOAc (200 ml) was added, the solution washed with water, dried over magnesium sulphate and evaporated. The crude product was purified by chromatography on silica with 4: 1 iso- hexane: EtOAc as eluent to give the title compound (17.9 g, 90%) as a white solid. HNMR 8 : 1.42 (s, 9H), 2.78 (dd, 1H), 3.00 (dd, 1H), 4.40 (m, 1H), 4.85 (M, 1H), 4.95 (m, 1H), 6.30 (d, 1H), 7.10 (m, 4H). |
90% | With triethylamine In dichloromethane at 18 - 25℃; for 20h; | 10 (1R, 2S)-CIS-L-AMINO-2-HYDROXYINDAN (12.0 g, 80.5 mmol) was dissolved in DCM (500 mL) and triethylamine (22.4 mL, 161 mmol). Di-tert-butyl dicarbonate (22.0 g, 100 mmol) in DCM (50 mL) was added and the mixture stirred at room temperature for 20 h then evaporated. EtOAc (200 mL) was added, the solution washed with water, dried over magnesium sulphate and evaporated. The crude product was purified by chromatography on silica with 4: 1 iso-hexane: EtOAc as eluent to give the title compound (17.9 g, 90%) as a white solid. 1H NMR S : 1.42 (s, 9H), 2.78 (dd, 1H), 3.00 (dd, 1H), 4.40 (m, 1H), 4. 85 (m, 1H), 4.95 (m, 1H), 6. 30 (d, 1H), 7.10 (m, 4H). |
In methanol for 1h; Heating; | ||
With anhydrous sodium carbonate In tetrahydrofuran; lithium hydroxide monohydrate for 1.5h; | Step (i): tert-butyl N- [(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-i-yij carbamate Di-tert-butyl dicarbonate (3.42 mL, 14.75 mmoi) as a solution in THF (4 mL) was added to a stirred suspension of (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol (2.0 g, 13.41 mmol) and Na2CO3 (2.84.g, 26.8 mmol) in THF (12 mL) and water (12 mL). After stirring for 1.5hours the reaction mixture was partitioned between water and EtOAc. The organics were separated, dried (phase separator) and concentrated in vacuo to afford the title compound. 1H NMR (300 MHz, DMSO-d6) ö ppm 1.45 (s, 9 H), 2.69 - 2.86 (m, 1 H), 2.94 - 3.08 (m, 1 H), 4.33 - 4.47 (m, 1 H), 4.82 - 5.04 (m, 2 H), 6.28 - 6.42 (m, 1 H), 7.12 - 7.24 (m, 4 H) | |
With triethylamine In acetonitrile at 20℃; for 3h; | Preparation of Compound S10 The Compound 10-1 was dissolved in acetonitrile, then triethylamine (2 eq) and BOC anhydride (1.05 eq) were added to the solution. After stirring at room temperature for 3 hours, the raw materials were completely reacted. Then the solvent was dried by rotary evaporation, and Compound 10-2 was obtained by silica gel column chromatography (DCM : MeOH = 30 : 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium carbonate In dichloromethane; water at -5 - 25℃; for 1h; | 9.B Step B: Preparation of 21B Na2CO3 (MW 105.99, 1.5 equ, 8.8 g) dissolved in 82 mL water. Add a solution of (1R,2S)-aminoindanol 21A (MW 149.19, 55.0 mmol, 8.2 g) in 160 mL CH2Cl2. Cool to -50 C. and add propionyl chloride (MW 92.53, d 1.065, 1.3 equ, 6.2 mL). Warm to 250 C. and age 1 h. Separate layers and dry organic (magnesium sulfate). Concentrate in vacuo to afford 21B (MW 205.26, 10 g) in 89% isolated yield. |
With triethylamine In tetrahydrofuran at 45 - 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With triethylamine In dichloromethane at 0℃; for 1.5h; | |
95% | With triethylamine In dichloromethane at 0℃; for 1.5h; | |
1.15 g | With triethylamine In dichloromethane at -60 - 20℃; for 1h; |
With triethylamine In dichloromethane | N-(3'-methanethiosulfonatopropyl)-(3aR-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]-oxazol-2-one((R)-1i) (1R,2S)-cis-1-amino-2-indanol (0.980 g, 6.569 mmol) was placed in a round-bottomed flask and a dry Ar atmosphere was established. Dry CH2Cl2 (50 mL) and Et3N (1.9 mL, 13.63 mmol) were added, and the resulting solution was cooled to -60° C. On addition of triphosgene (0.64 g, 2.157 mmol), the cooling bath was removed, and the reaction was allowed to warm to 20° C. over one hour. The reaction was then poured into CH2Cl2 (100 mL) and H2O (50 mL) and the aqueous phase was extracted with CH2Cl2 (3*100 mL). After drying with MgSO4, the organic layer was evaporated under reduced pressure to give (3aR-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]-oxazol-2-one, (R)-24 (1.15 g, quantitative) as white crystals, which was of sufficient purity for the next step in the reaction sequence. An analytical sample was recrystallized from CH2Cl2/hexanes. mp 205.5-206.5° C.; [Ghosh et al. (1992) J. Chem. Soc. Chem. Commun. 1673-1674 for enantiomer mp 205° C.]; [α]25D=+107.7 (c 1.25, CHCl3); [Id. for enantiomer [α]25D=-79.4 (c 1.4, CHCl3)]. IR (KBr) 3255, 1752, 1707 cm-1; 1H NMR (acetone-d6) δ 7.24-7.43 (4H, m), 5.39 (1H, t, J=7.5 Hz), 5.21 (1H, d, J=7.0 Hz), 3.42 (1H, dd, J=17.7, 6.2 Hz), 3.20 (1H, d, 17.9 Hz), 2.90 (1H, br s); 13C NMR (acetone-d6) δ 159.1, 142.5, 141.0, 129.7, 128.3, 126.2, 125.8, 80.8, 61.7, 39.3; HRMS (FAB+) m/z: calcd for C10H9NO2+H, 176.0771; found, 176.0681. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With sodium acetate In acetonitrile at 20℃; Electrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With magnesium sulfate In ethanol for 16h; | |
In dichloromethane at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With zinc trifluoromethanesulfonate In toluene for 48h; Heating; | |
71% | Stage #1: 2,2-dimethylmalononitrile With zinc trifluoromethanesulfonate In toluene for 0.0833333h; Inert atmosphere; Stage #2: (1R,2S)-1-Amino-2-indanol In toluene for 24h; Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In dichloromethane at 45℃; for 24h; Inert atmosphere; | |
67% | In dichloromethane at 45℃; for 18h; Inert atmosphere; | |
67% | In dichloromethane at 45℃; for 18h; Inert atmosphere; |
65% | In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 96h; | 1 Preparation of [3AR- [2 (3'aR*, 8'aS*), 3 AP, 8 AP]]- (+) -2, 2'-methylene BIS- [3A, 8a-dihydro-8H-indeno- [1, 2-d]-oxazole (bis (oxazoline) (4) ) A 3 L round bottom flask was charged with diethyl MALONIMIDATE dihydrochloride (25.8 g, 0.112 moles, 1.0 equiv. ) and DIMETHYLFORMAMIDE (DMF) (320 mL). The mixture was cooled in an ice bath. To this suspension was added (LR, 2S)- (+)-CIS-L-AMINO-2- indanol (40 G, 0.268 moles, 2.4 equivalents), in portions, over twenty minutes. The ice bath then was removed, and the reaction allowed to warm to room temperature, during which time the reaction product precipitated from the reaction. After four days stirring at room temperature, the reaction was filtered. The collected white solid was suspended in CH2Cl2 (450 ML). The mixture then was washed with water (260 ML) and brine (260 mL). The organic lay- er was dried over sodium sulfate (NA2SO4), filtered, and concentrated to an off-white solid. Drying overnight under vacuum provided 23.9 g (65% yield) of the bis (oxazoline) (4). 1H NMR (300 MHZ/CDCL3) : 6 7. 45 (m, 2H, Ar-H); 7.27-7. 21 (m, 6H, AR-H) ; 5.56 (d, J=7.9 Hz, 2H, N-CH); 5.34 (M, 2H, O-CH) ; 3.39 (DD, J=7.0, 18. 0 Hz, 2H, Ar-CHH); 3 : 26 (S, 2H, -CH2-0); 3.16 (d, J=18.0 Hz, 2H, 14-CHH). The'NMR is consistent with the peak assignments made in WO 00/15599. |
40% | In dichloromethane Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In tetrahydrofuran at 0 - 20℃; | |
88% | In dichloromethane at 20℃; | |
In tetrahydrofuran at 0 - 20℃; |
In dichloromethane at 20℃; | ||
In tetrahydrofuran for 0.5h; Cooling with ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With zinc(II) chloride In chlorobenzene for 48h; Heating; | |
58% | With zinc(II) chloride In chlorobenzene for 24h; Reflux; | General procedure for the synthesis of 2-(o-aminophenyl)oxazolines 12a-b and 13 General procedure: An oven dried two-necked flask was washed with argon and charged with 2-aminobenzonitrile (118 mg, 1 mmol), the appropriate amino alcohol, freshly flame dried ZnCl2 (405 mg, 3 mmol) and anhydrous chlorobenzene (6 mL). The mixture was stirred at reflux for 24 h. The solvent was then removed under reduced pressure and the residue was stirred with 30% NaOH for 0.5 h. The product was extracted with dichloromethane and purified by flashcolumn chromatography on silica gel. |
54% | With zinc(II) chloride In chlorobenzene for 24h; Reflux; | General procedure for the synthesisof 2-(o-aminophenyl)oxazolines 8a-8h General procedure: An oven-dried two-necked flask was washed with argonand charged with 118 mg 2-aminobenzonitrile (1 mmol) or136 mg 2-amino-5-fluorobenzonitrile (1 mmol) or 163 mg2-amino-5-nitrobenzonitrile (1 mmol), the appropriateamino alcohol (1.5 mmol), 405 mg freshly flame dried ZnCl2(3 mmol), and 10 cm3anhydrous chlorobenzene. The mixturewas stirred under reflux for 24 h. The solvent was thenremoved under reduced pressure and the residue was stirredwith 30% NaOH for 0.5 h. The product was extracted withethyl ether and purified by flash column chromatographyon silica gel. 2-[(4S)-4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl]aniline(8a) Compound 8a was prepared from 118 mg 2-aminobenzonitrile(7a, 1 mmol) and 205 mg S-phenylglycinol(6a, 1.5 mmol). White crystals; yield 203 mg (85%). All thephysical and spectroscopic data are with agreement with theones published in Ref. [29]. |
With zinc(II) chloride In chlorobenzene for 24h; Reflux; | 4.2. Synthesis of 2-[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2-d]-oxazol-2-yl]aniline 7 and 2-[(4R,5S)-4,5-diphenyl-4,5-dihydrooxazol-2-yl]aniline 8 General procedure: An oven dried two-necked flask was washed with argon and charged with 2-aminobenzonitrile (118mg, 1mmol), (1R,2S)-1-amino-2-indanol 5 or (1S,2R)-2-amino-1,2-diphenylethanol 6 (1.2mmol), freshly flame dried ZnCl2 (405mg, 3mmol), and anhydrous chlorobenzene (6mL). The mixture was stirred at reflux for 24h. The solvent was then removed under reduced pressure and the residue was stirred with 30% NaOH for 0.5h. The product was extracted with dichloromethane and purified by flash column chromatography on silica gel (hexane/EtOAc, 5:1); 4.2.1 2-[(3aR,8aS)-8,8a-Dihydro-3aH-indeno[1,2-d]oxazol-2-yl]aniline 7; All the physical and spectroscopic data of compound 7 are in agreement with the published ones.14 | |
With zinc(II) chloride In chlorobenzene for 24h; Inert atmosphere; Reflux; | 2.1.1. Synthesis of 4-fluoro-2-[(4S)-4-isopropyl-4,5-dihydro-1,3-oxazol-2-yl]aniline (3b). General procedure: An oven-dried two-necked flaskwas flushed with argon and charged with 2-amino-5-fluorobenzonitrile(349 mg, 2.6 mmol), (S)-valinol (309 mg, 3.0 mmol),freshly flame-dried ZnCl2 (1005 mg, 7.7 mmol) and anhydrouschlorobenzene (20 ml). Themixture was stirred under reflux for24 h. The solvent was then removed under reduced pressureand the residue stirred with 30% NaOH for 0.5 h. The productwas extracted with ethyl ether and purified by flash columnchromatography on silica gel (CH2Cl2/hexanes, 5:3.5 v/v) andrecrystallized from ethanol to give a white solid.Analytical data for 3b: yield 535 mg (2.4 mmol), 94%; whitecrystals | |
With zinc(II) chloride In chlorobenzene at 130℃; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In dichloromethane for 17h; | |
96% | In dichloromethane for 17h; Molecular sieve; | 3 Synthesis of (1R,2S)-cis-1-Amino-2-indanol-derived oxazolidine Example 3 Synthesis of (1R,2S)-cis-1-Amino-2-indanol-derived oxazolidine A mixture of (1R,2S)-1-aminoindan-2-ol (150 mg, 1 mmol) and cyclohexanone (98 mg, 1 mmol) was stirred in CH2Cl2 in the presence of molecular sieve (4 Å) for 17 h. Filtration and removal of the solvent under reduced pressure gave a colorless oil (220 mg, 96%). 1H NMR (300 MHz, CDCl3) δ=1.35-1.74 (m, 10H), 2.38 (bs, 1H), 3.06 (dd, J=1.2 Hz, 18.8 Hz, 1H), 3.23 (dd, J=6.4 Hz, 18.8 Hz, 1H), 4.81 (ddd, J=1.2 Hz, 6.4 Hz, 6.4 Hz, 1H), 4.87 (d, J=6.4 Hz, 1H), 7.18-7.26 (m, 3H), 7.38 (m, 1H). 13C NMR (75 MHz, CDCl3) δ=22.6, 22.9, 24.4, 34.3, 36.4, 38.2, 67.2, 78.5, 97.1, 124.2, 124.5, 126.1, 127.3, 140.5, 142.0. Anal. Calcd C15H19NO: C, 78.56; H, 8.35; N, 6.11. Found: C, 78.42; H, 8.32; N, 6.13. For comparison, we prepared a (1R,2S)-cis-1-amino-2-indanol-derived oxazolidine 2 using cyclohexanone instead of cyclohexanedione and tested its catalytic performance under the same reaction conditions. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With formic acid In toluene Heating; | |
90% | In toluene Heating / reflux; | 1 Synthesis and Characterization of 1 A mixture of cis-(1R,2S)-1-aminoindan-2-ol (5.0 g, 33.6 mmol) and 1,2-cyclohexanedione (1.8 g, 16.3 mmol) was refluxed in toluene using a Dean-Stark trap in the presence of catalytic amounts of formic acid until no water was formed. After cooling to room temperature, the solvent was removed under reduced pressure. The crude residue was dissolved in small amounts of dichloromethane and purified by crystallization upon addition of acetonitrile. Three crystallizations gave 5.5 g (14.5 mmol, 90%) of the product as a white powder. 1H NMR (300 MHz, CDCl3) δ=0.87 (d, J=12.0 Hz, 2H), 1.26-1.46 (m, 6H), 2.83 (bs, 2H), 3.13 (d, J=2.9 Hz, 4H), 4.69-4.74 (m, 2H), 5.01 (d, J=5.3 Hz, 2H), 7.17-7.26 (m, 6H), 7.37-7.43 (m, 2H). 13C NMR (75 MHz, CDCl3) δ=23.9, 37.2, 39.6, 69.9, 81.9, 102.1, 125.9, 126.0, 127.7, 128.6, 141.8, 144.6. Anal. Calcd C24H26N2O2: C, 76.98; H, 7.00; N, 7.48. Found: C, 76.66; H, 6.86; N, 7.40.; For example, employing (1R,2S)-cis-1-amino-2-indanol in the acid-promoted reaction with 1,2-cyclohexanedione, bisoxazolidine 1 was obtained in 90% yield and 99% de (FIG. 1B). It was shown that compound 1 was produced with excellent diastereoselectivity and exclusive formation of the (S,S)-N,O-diketal by crystallographic analysis: careful evaporation of a solution of 1 in chloroform gave the single crystal suitable for crystallographic analysis (CDCC602445). (Crystal structure data: C24H26N2O2, monoclinic, space group P21, a=16.9199(16) , b=5.5487(5) , c=23.585(2) , α=90.00°, β=108.5190(10)°, γ=90.00°, V=2099.6(3) 3, Z=4, ρcalcd=1.367 g cm-3, T=173 K.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.8 % ee | Stage #1: ethyl 4-[2-(difluoromethoxy)-4-(trifluoromethyl)phenoxy]-1a,6b-dihydro-1H-cyclopropa[b][1]benzofuran-1-exo-carboxylate With lithium hydroxide; water In tetrahydrofuran; methanol at 20℃; for 3h; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water; toluene Stage #3: (1R,2S)-1-Amino-2-indanol In tetrahydrofuran; methanol; water; toluene at 75 - 85℃; for 0.25h; | 2 THF (30 L), water (15 L), and LiOH (5 equiv.) were added to a 100 L RBF containing the solution of the ester from the previous step in MeOH. The mixture immediately became dark and exothermed to 38° C. The reaction was aged for 3 h at ambient temperature and was then transferred to a cylindrical reaction vessel. Toluene (30 L) and 5 N HCl (1.1 equiv.) were added, and the layers were separated. The organic layer was washed with water (2×30 L). The organic layer was then concentrated to -29L with azeotropic removal of water. LiCl precipitate formed during the concentration. Ecosorb C905 (50 wt %, 2.89 kg) was added to the thin slurry, and the mixture was then aged at ambient temperature for 2 h, filtered through solka floc, and rinsed with toluene (23 L). The filtrate was concentrated to 29 L, and (R,S)-CAI, (R,S)-cis-aminoindanol (0.96 equivalents compared with the assayed amount of hydrolyzed ester) was added. The mixture was warmed to 85° C. to dissolve all solids. The mixture was then cooled to 75° C., and the CAI salt began to crystallize. The mixture was aged 15 min at 75° C., and then heptane (13.5 L) was added over 1 h. The mixture was allowed to slowly cool to rt. The mixture was filtered. The solid product was washed with 2:1 toluene/heptane (18 L), and was then dried under nitrogen for 5 days. The isolated product was 98.6% pure solid, 98.0% ee.The CAI salt (5900 g of 98.6 wt.% product from above) was dissolved in toluene (53 L) at 85° C. and was then cooled to 70° C. to give a thin slurry. Heptane (18L) was added over 1 h while maintaining the temperature at 65-70° C. The mixture was allowed to cool to rt over 3 h and was then filtered. The filter cake was dried under nitrogen for 2 days. The isolated product purity was >99A % and 98.8% ee. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane at 0℃; for 0.5h; | 39.A To a mixture of (1R,2S)-1-amino-2-indanol (500 mg, 3.35 mmol) and triethylamine (0.51 mL, 3.69 mmol) in anhydrous CH2Cl2 at 0° C. was added chloroacetyl chloride (0.295 mL, 3.69 mmol) dropwise. The resulting mixture was stirred for 30 min, quenched with saturated aqueous NaHCO3 (15 mL) and then extracted with EtOAc (2×75 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc 70:30 to 0:100, to give the title compound. MS: m/z=226 (M+1). | |
With triethylamine In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With caesium carbonate In toluene at 20 - 110℃; for 2h; | 1 EXAMPLES; Preparation 1; (1R,2S)-1-(3,6-Diethyl-pyrazin-2-ylamino)-indan2-ol; To a nitrogen purged 200 Liter glass lined reactor was added (1R,2S)-(+)-cis-1-amino-2-indanol (2.5 kg, 16.1 moles, 1.5 eq), palladium (II) acetate (72 g, 0.3 moles, 3 mole % ), 2,2'-bis(diphenylphosphino)-1,1'-binapthyl (200 g, 0.3 moles, 3 mole % ) and cesium carbonate (7.0 kg, 21.5 moles, 2.0 eq) followed by toluene (65 L, drum stock). To the stirring white suspension was added 3-Chloro-2,5-diethyl-pyrazine (1.83 kg, 10.7 moles, 1.0 eq) at room temperature and the contents were heated to reflux (110° C.) for 2 h, at which time the reaction was judged complete by HPLC (4 drops of reaction mixture quenched into water and then extracted into 1 mL MTBE, remove solvent and dilute with 1.5 mL CH3CN/water). To the ambient reaction mixture was added methyl-t-butyl ether (45 L, drum stock) and water (45 L) and the layers separated. The organic layer was washed a second time with water (45 L) then extracted with methyl-t-butyl ether (45 L, drum stock). The combined organic layers were then concentrated under vacuum to a minimum volume. Dimethyl formamide (4 gal, E&M Science) was added and the resultant black solution was transferred into a 20-L bottle. A yield for (1R,2S)-1-(3,6-Diethyl-pyrazin-2-ylamino)-indan2-ol using quantitative HPLC (2.27 kg, 73%) was determined. This material was used without further purification. HPLC retention time of the title compound is 2.1 min. Column 150 mm×4.6 mm, Luna 5μphenyl-hexyl; 50/50 CH3CN/water+0.1% TFA with gradient to 75/25+0.1% CH3CN/water+0.1% TFA.IR (diffuse reflectance) 3435, 3241, 2962, 2935, 2912, 2873, 1581, 1547, 1500, 1453, 1184, 1163, 1047, 744, 733 cm-1; OAMS supporting ions at: ESI+384.0; MS (Cl ) m/z 284 (MH+); HRMS (FAB) calcd for C17H21N3O+H1 284.1763, found 284.1754. [[25D=12(c 0.55, methylene chloride); Anal. Calcd for C17H21N3O: C, 72.06; H, 7.47; N, 14.83. Found: C, 72.15; H, 7.53 N, 14.42. |
65% | With sodium t-butanolate In toluene at 100℃; for 2h; | 1 Example 1 The preparation of (lR, [2S)-1- ( {3, 6-DIETHYL-5- [ (4-METHYLPYRIDIN-2-YL)] oxy] pyrazin-2- [YL} AMINO)-2, 3-DIHYDRO-LH-INDEN-2-OL] (Chart F, Step 3); (lR, [2S)-1-[(3,] 6-diethylpyrazin-2-yl) amino]-2, [3-DIHYDRO-LH-INDEN-2-OL] (Chart F, Step 1) Example 1 The preparation of (lR, [2S)-1- ( {3, 6-DIETHYL-5- [ (4-METHYLPYRIDIN-2-YL)] oxy] pyrazin-2- [YL} AMINO)-2, 3-DIHYDRO-LH-INDEN-2-OL] (Chart F, Step 3) (lR, [2S)-1-[(3,] 6-diethylpyrazin-2-yl) amino]-2, [3-DIHYDRO-LH-INDEN-2-OL] (Chart F, Step 1) A solution of 3-chloro-2,5-diethylpyrazine (171 mg, 1.0 mmol), [(1R,] [2S)- (+)-] [CIS-L-AMINO-2-INDANOL] (298 mg, 2.0 mmol), tris (dibenzylideneacetone) dipalladium (0) (28 mg, 0.03 mmol), and 2- (di-tertbutylphosphino) biphenyl (18 mg, 0.06 mmol) in toluene (2.0 mL) was purged with nitrogen and treated with sodium t-butoxid (135 mg, 1.4 [MMOL).] The resulting brown suspension was heated to [100 °C] for 2 hours. At this time, the reaction was quenched with a saturated water solution of [NAHC03] and extracted twice with ethyl acetate (20 [ML).] The combined organics were washed with brine (15 [ML),] dried over [MGS04,] filtered, and concentrated to give a black solid. This material was purified by Biotage MPLC (40 g column, 25% ethyl acetate/heptane) to afford 184 mg (65%) of [(LR,] [2S)-1- [ (3,] 6-diethylpyrazin-2- yl) amino]-2, [3-DIHYDRO-LH-INDEN-2-OL] as a light purple solid. MS (ESI+) for [CL7H2LN3O] [M/Z] 284.0 (M+H) [+.] |
With sodium t-butanolate In toluene at 100℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triethylamine In tetrahydrofuran at 10 - 25℃; for 20h; | 2 Method 2; N-r (lR 2R)-2-Amino-2, 3-dihydro-lH-inden-1-yllmethanesulfonamide; (lR, 2S)-1-Amino-2-hydroxyindan (3. 0g, 20mmol) was dissolved in dry THF (40 ml) and triethylamine (8.4 ml, 60. 0mmol) at 10°C. Methane sulphonyl chloride (5. 0g, 44. 0mmol) dissolved in THF (10ml) was added at such a rate that the internal temperature remained below 15°C. Following the addition the mixture was stirred at room temperature for 20hours and then evaporated. To the residue was added EtOAc (100 ml) and the mixture washed with saturated aqueous sodium bicarbonate and then water. The organic solution was dried over magnesium sulphate and evaporated to give (lR, 2S)-1-methanesulphonamido-2- methylsulphonyloxyindan (5.7g, 93%) as a pale yellow solid. 'H NMR : 3.25 (m, 2H), 3.10 (s, 3H, ), 3.20 (s, 3H), 5. 15 (m, 1H), 5. 35 (m, 1H), 7.3 (m, 4H), 7.90 (m, 1H) ; m/z 304.2. |
With triethylamine In dichloromethane at 0 - 20℃; | e e) (1 R,2S)-1-methanesulphonylamino-indan-2-yl methanesulphonate (B-1a)B-1a(1 R,2S)-1-amino-2-indanol (300 mg, 2.01 mmol) is in suspended 10 ml. DCM, combined with triethylamine (1.68 ml_, 12.1 mmol) and cooled to 0°C. Then methanesulphonic acid chloride (467 μl_, 6.03 mmol) is added dropwise and the reaction mixture is left to warm up to RT. The reaction mixture is stirred for 1 h at RT and once the reaction is complete it is mixed with water and extracted with DCM. The organic phase is dried on MgSO4, filtered, the filtrate is evaporated down and the crude product B-1a (HPLC-MS: tRet = 1.03 min; MS (M-H)" = 304) is used in the subsequent reactions without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
184 mg (65%) | With sodium hydrogencarbonate; In water; ethyl acetate; toluene; | Preparation 1 (1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol A solution of 3-chloro-2,5-diethylpyrazine (171 mg, 1.0 mmol), (1R,2S)-(+)-cis-1-amino-2-indanol (298 mg, 2.0 mmol), tris(dibenzylideneacetone)dipalladium (0) (28 mg, 0.03 mmol), and 2-(di-tertbutylphosphino)biphenyl (18 mg, 0.06 mmol) in toluene (2.0 mL) was purged with nitrogen and treated with sodium tertbutoxide (135 mg, 1.4 mmol). The resulting brown suspension was heated to 100° C. for 2 hours. At this time, the reaction was quenched with a saturated water solution of NaHCO3 and extracted twice with ethyl acetate (20 mL). The combined organics were washed with brine (15 mL), dried over MgSO4, filtered, and concentrated to give a black solid. This material was purified by biotage MPLC (40 g column, 25percent ethyl acetate/heptane) to afford 184 mg (65percent) of the title compound as a light purple solid. IR (diffuse reflectance) 3435, 3241, 2962, 2935, 2912, 2873, 1581, 1547, 1500, 1453, 1184, 1163, 1047, 744, 733 cm-1; OAMS supporting ions at: ESI+384.0; MS (CI) m/z 284 (MH+); HRMS (FAB) calcd for C17H21N3O +H1 284.1763, found 284.1754. [alpha]25D=12 (c 0.55, methylene chloride); Anal. Calcd for C17H21N3O: C, 72.06; H, 7.47; N, 14.83. Found: C, 72.15; H, 7.53; N, 14.42. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: (1R,2S)-1-Amino-2-indanol With sodium hydride In tetrahydrofuran at 0 - 70℃; Inert atmosphere; Stage #2: (E)-1-Bromo-2-butene In tetrahydrofuran at 70℃; for 2.16667h; | |
64% | With sodium hydride In tetrahydrofuran at 70℃; for 0.666667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran | 107.A Step A. To a solution of 7-methyl-pyrazolo[l,5-a]pyrimidine-2,5-dicarboxylic acid 2-methyl ester (47 mg, 0.2 mmol) and (IR, 2S)- 1 -amino-2-hydroxyindane (30 mg, 0.2 mmol) in THF (3 mL) were added triethylamine (42 μL, 0.21 mmol), EDCI (40 mg, 0.21 mmol) and HOAt (15 mg, 0.21 mmol). The mixture was stirred overnight and then concentrated. The remaining residue was purified by chromatography to give (IR, 2S)-5-(2-hydroxy-indan-l-ylcarbamoyl)-7-methyl- pyrazolo[l,5-a]pyrimidine-2-carboxylic acid methyl ester (60 mg, yield 82%). MS (M + H): 367. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In tetrahydrofuran at 20℃; | General procedure: A solution of the 7 in THF (0.6 M) was added to a stirred solution of the isothiocyanate 6 in THF (0.6 M) at room temperature. After 48 h, the solvent was removed under reduced pressure. And finally, the residue was purified by column chromatography to yield the desired product 2a (yield 81%). 2b and 2c are known compounds, which were synthesized according to the similar procedure. |
61% | In tetrahydrofuran at 20℃; | |
In dichloromethane at 25℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | Stage #1: carbonic acid 4-nitrophenyl ester pyridin-4-ylmethyl ester; (1R,2S)-1-Amino-2-indanol With dmap; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h; Stage #2: With hydrogenchloride In diethyl ether; dichloromethane | 10 To a solution of (li?,2S)-(+)-c-l-amino-2-indanol (149 mg, 1.0 mmol), 4-nitrophenyl (pyridin-4-yl)methyl carbonate (Intermediate 1; 274 g, 1.0 mmol) and DIPEA (354 μL, 2.0 mmol) in DMF (5 mL) was added DMAP (catalytic amount). The reaction mixture was stirred at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (50 mL) and washed with IM aq Na2CO3 solution (5 x 30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase chromatography (gradient eluting with MeOH in DCM from 0% to 3%). The residue was dissolved in DCM (30 mL) and excess 2M ηCI in Et2O was added. The resulting precipitate was collected by filtration and dried in vacuo to give (pyridin-4-yl)methyl (li?,25)-2,3-dihydro-2-hydroxy-l/f-inden-l-ylcarbamate hydrochloride (70 mg, 22%) as a white solid.Analytical ηPLC: purity 97.1% (System A, Rτ = 5.61 min); Analytical LCMS: purity 100% (System C, Rτ = 4.07 min), ES+: 285.0 [MH]+. HRMS calcd for Ci6Hi6N2O3: 284.1161, found 284.1164. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With dicarbonylacetylacetonato rhodium(I); hydrogen; toluene-4-sulfonic acid; 6,6′-[(3,3′-di-tert-butyl-5,5′-dimethoxy-1,1′-biphenyl-2,2′-diyl)bis(oxy)]bis(di-benzo[d,f][1,3,2]dioxaphosphepin) In tetrahydrofuran at 70℃; for 1h; Microwave irradiation; Sealed tube; optical yield given as %de; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With dicarbonylacetylacetonato rhodium(I); hydrogen; toluene-4-sulfonic acid; 6,6′-[(3,3′-di-tert-butyl-5,5′-dimethoxy-1,1′-biphenyl-2,2′-diyl)bis(oxy)]bis(di-benzo[d,f][1,3,2]dioxaphosphepin) In tetrahydrofuran at 70℃; for 1h; Microwave irradiation; Sealed tube; optical yield given as %de; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 20℃; Cooling with ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With nitric acid In water at 20℃; for 0.333333h; | 1 Aq. Nitric acid (69%, 3.38 rnL, 1 eq)), was added dropwise to a stirred suspension of (IR, 2S)-cis- l-Aminoindan-2-ol (6.65 g, 44.57 mmol) in water (25 rnL) for 20 min.Heterogeneous reaction mixture slowly turned to a clear solution. The reaction mixture was concentrated under reduce pressure without heating the contents above 35 0C. The crude viscous residue was treated with Et2O (100 mL) followed by the addition of water (0.5 mL) and stirred the contents to form a nice white crystalline solid. The solid formed collected by filtration and dried under vacuum over P2O5 to provide (IR, 2S)-C/*- l-Aminoindan-2-ol nitrate salt (9.2 g, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In isopropyl alcohol; at 0℃; for 9h;Reflux; | General procedure: Compounds 2-5 were synthesized using a modified procedure originally reported by Roehrig et al.28 To a cooled solution of <strong>[181140-34-1](R)-(-)-N-(2,3-epoxypropyl)phthalimide</strong> 1 (102 mg, 0.50 mmol) in 10 mL of 2-propanol, amine or aminoalcohol (0.6 mmol, 1.2 equiv) in 10 mL of 2-propanol was added at 0 C and stirred for 1 h. It was then refluxed for 8 h. After the completion of the reaction, the solvent was removed under reduced pressure and the crude product was purified by flash chromatography on silica gel (CHCl3/MeOH 1:20 as eluent) to afford 2-5 as white crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: L-N-Boc-Ala With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: (1R,2S)-1-Amino-2-indanol In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72%; 15% | General procedure: Constant current electrolyses (I = 25 mA cm-2) were performed under a nitrogen atmosphere, at 20C, using an Amel Model 552 potentiostat equipped with an AmelModel 731 integrator. All the experiments were carried out in a divided glass cell separated through a porous glass plug filled up with a layer of gel (i.e., methylcellulose 0.5% vol dissolved in DMF-Et4NPF6 1.0 mol dm-3); Pt spirals (apparent areas 0.8 cm2) were used both as cathode and anode. MeCN-Et4NPF6 0.1 mol dm-3 was used as solvent-supporting electrolyte system (catholite: 20 cm3; anolite: 5 cm3).1 mmol of substrate was present in the catholyte (except for D-cycloserine, which was added to the catholyte after the end of the electrolysis). After 145 C (if not otherwise stated) were passed, the current was switched off and 1 mmol of alkylating agent was added to the catholyte. The solution was kept under stirring at room temperature for 2 hours, than the solvent was evaporated under reduced pressure and the residue was extracted three times with diethyl ether. The products were purified by flash column chromatography, using a mixture of ethyl acetate/light petroleum ether 2/8 in volume. The reactions on D-cycloserine were carried out following the general method, but the substrate was added to the catholyte after the end of the electrolysis. After 15 minutes at room temperature, the alkylating agent was added and the solution was kept under stirring at rt for 2 hours. The solvent was evaporated under reduced pressure and the residue was treated with 1 cm3 of saturated acqueous NaHCO3 and 1 mmol of ethyl chloroformate, at 0C, for 2 h. The solution was then acidified with diluted HCl (pH 4) and extracted with diethyl ether. The products were purified by flash column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In 1,4-dioxane for 72h; Inert atmosphere; Reflux; | 9 N1-(4-chloro-3-fluorophenyl)-N2-((lR,2S)-2-hydroxy-2,3-dihydro-lH-inden-l- yl)oxalamide (TK-II-103). To a solution containing ethyl 2-(4-chloro-3- fluorophenylamino)-2-oxoacetate (1) (1.73 g, 7.05 mmol) in 20 mL dioxane in a round- bottom flask was added (lR,2S)-l-amino-2,3-dihydro-lH-inden-2-ol (1.16 g, 7.76 mmol) and both a stir bar and a reflux condenser were equipped. The reaction was heated to reflux for 72 hours and then allowed to cool to room temperature. The crude reaction mixture was concentrated in vacuo. The solid was collected by filtration with a 1 : 1 mixture of hexanes and dichloromethane to give 2.04 g (83%) of TK-II-103 as an off-white flakey solid; [α]29D = -1 12.1° (c = 0.48, DMSO); H NMR (500 MHz, DMSO-ifc) δ 1 1.19 (s, 1H), 8.36 (d, J = 8.7 Hz, 1H), 7.97, (dd, J = 2, 1 1.7 Hz, 1H), 7.77, (d, J = 8.8 Hz, 1H), 7.59, (t, J = 8.7 Hz, 1H), 7.28-7.18, (m, 4H), 5.46, (d, J= 4.9 Hz, 1H), 5.25, (dd, J= 5.2, 8.6 Hz, 1H), 4.52, (dd, J = 4.6, 8.6 Hz, 1H), 3.14, (dd, J = 4.9, 16.2 Hz, 1H), 2.88, (d, J = 16.1 Hz, 1H); 13C NMR (125 MHz, DMSO-i/e) δ 159.3, 158.8, 156.8, (d, JCF = 242.5 Hz), 141.0, 140.8, 138.2, (d, JCF = 10 Hz), 131.6, 127.7, 126.5, 125.0, 124.1, 1 17.5 (d, JCF = 2.9 Hz), 1 14.5 (d, JCF = 17.5 Hz), 108.6, (d, JCF = 25 Hz), 71.6, 56.9. HRMS (ES+) m/z 371.0572 [(M+Na)+; calcd for C17H14CIFN2O3: 371.0575]. |
In ethanol at 150℃; for 1h; sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With triethylamine In ethanol; dichloromethane at 20℃; for 72h; | 4.2 Representative procedure for the synthesis of squaramides catalysts 1a-d and 4 General procedure: To a solution of 7 (0.1 mmol) in DCM (10 mL) with TEA (0.12 mmol) was added a solution of amine 8 in ethanol at room temperature. After 72 h, the reaction mixture was concentrated and subjected to column chromatography to afford product 1a (72%) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With N-Bromosuccinimide; sulfuric acid; at 0℃; | Example 26: Kinetic Resolution of Racemic N- Heterocycles with a Recyclable , Polymer- Supported Reagent This refers to the synthesis of a robust and recyclable polystyrene supported reagent and its use for the facile resolution of chiral amines. The resolutions are conducted simply by mixing the racemic amine and this reagent (~0.6 equiv) followed by aqueous extraction or column chromatography to separate the acylated product from the enantioenriched recovered amine. The reagent can be recycled dozens of times without loss of efficiency or selectivity. This approach is useful for obtaining enantiopure amines from their racemates, as well as preparing enantioenriched amides with groups that can be cleaved under mild conditions.Preparation of solid-supported amine resolving agent 9. Reagents and conditions: a) TFA:H2S0„ (3:1) 0 C, then NBS (1.01 equiv), 80%; b) N, O-bis ( trimethylsilyl ) acetamide (1.1 equiv), CH3CN, 23 C to 75 C , then Mo05*PyHMPA (MoOPH) (1.2 equiv), CH2C12, 23 C, 73%; c) benzylacrylate (1.50 equiv), Pd(OAc)2 (0.10 equiv), P(o-tolyl)3 (0.21 equiv) , Et3N (5.00 equiv) , CH3CN, 23 C to 75 C, 65%; d) Ac20 (1.10 equiv), EtOAc, 23 C to 45 C, then Pd/C (10 wt%), H2; then 1 M LiOH, 73%; e) 7(0.50 equiv), HATU (0.95 equiv), DMAP (1.00 equiv), Hiinig' s base (3.00 equiv), DMF; f) 3-phenylpropanoic anhydride, DMF, 45 C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of <strong>[2365-85-7]3-amino-4-fluorobenzoic acid</strong> (14) (1 .0 g, 6.4 mmol) in DMF (20 ml_) was added diisopropylethylamine (3.4 ml, 19.3 mmol) and HATU (2.45 g, 6.4 mmol). The reaction was stirred at room temperature for 30 minutes then (1 R,2S)-1 -amino-2,3- dihydro-1 H-inden-2-ol (15) (0.96 g, 0.64 mmol) was added and the stirring continued for 1 .5 hours. The reaction mixture was diluted with ethyl acetate and washed with sat NaHC03, water and brine. The organic layer was dried over magnesium sulfate, filtered and reduced to dryness. The crude product was purified by preparative mass trigger LCMS to afford 3-amino-4-fluoro-N-((1 R,2S)-2-hydroxy-2,3-dihydro-1 H-inden-1 - yl)benzamide (16) as a white yellow solid. 1 H NMR (400MHz, c/6-MeOH) delta 8.74 (dd, J = 4.8, 1 .6 Hz, 1 H), 8.44 (dd, J = 4.4, 1 .2 Hz, 1 H), 7.98 (s, 1 Hz), 7.15-7.55 (m, 4H), 5.55 (d, J = 5.2 Hz, 1 H), 4.69 (td, J = 8.4, 2.0 Hz, 1 H), 3.23 (dd, J = 16, 5.2 Hz,1 H), 3.01 (dd, J = 16.4, 2.0 Hz,1 H ), (MS m/z 287.1 (M+1 )+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: 4-(dimethylamino)picolinic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: (1R,2S)-1-Amino-2-indanol With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere; | 4-(Dimethylamino)-N-((1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)picolinamide Anhydrous DMF (25 mL) was charged to a dried reactor charged with 4-(dimethylamino)picolinic acid (1.80 g, 12.1 mmol) and O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (4.26 g, 13 mol) under nitrogen at normal room temperature. Agitation was started and isopropyl ethylamine (2.31 mL, 13 mmol) was charged to the slurry. After agitating the slurry for 30 minutes, a homogeneous solution was obtained. (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol (2.05 g) was charged to the reactor as a solid followed by diisopropyl ethylamine (2.31 mL, 13 mmol). The reaction was agitated at normal room temperature under argon for 18 hours. 40 mL of water was charged to the reactor dropwise over 1 hour. The resulting slurry was agitated at normal room temperature for 1 hour. The solids were collected by filtration and washed with water followed by heptane. The solids were dried in a vacuum oven with a nitrogen stream at 70° C. for 2 days to provide the intended product 4-(dimethylamino)-N-((1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)picolinamide as an off white solid (2.74 g, 76% yield). 1H NMR (400 MHz, DMSO-D6) δ 8.77 (d, J=8.58 Hz, 1H), 8.15 (d, J=5.8 9 Hz, 1H), 7.37 (d, J=2.8 Hz, 1H), 7.29-7.13 (m, 4H), 6.76 (dd, J=5.9, 2.8 Hz, 1H), 5.45 (d, J=4.7 Hz, 1H), 5.34 (dd, J=8.7, 5.1 Hz, 1H), 4.51 (dd, J=4.71, 4.71, 4.71 Hz, 1H), 3.14 (dd, J=16.2, 4.8 Hz, 1H), 3.05 (s, 6H), 2.86 (d, J=16.2 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium sulfate In methanol for 4h; Reflux; | |
With acetic acid In ethanol Reflux; | 4.4. General procedure for the preparation of hemisalenligands General procedure: The metallic precursors and the chiral ligands were obtained according to the procedure described by Riant et al. [17]. A round-bottomed flask was loaded with the appropriate amino-alcohol (1equiv.) in 5mL of ethanol. Next, 1equiv of the aldehyde and a few drops of acetic acid were added. The reaction was refluxed overnight. At the end of the reaction, the mixture was concentrated in vacuo. Purification by flash chromatography on silica gel or re-crystallization was carried out if necessary. | |
In chloroform at 25℃; for 1h; |
In ethanol Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In ethanol;Reflux; | General procedure: The metallic precursors and the chiral ligands were obtained according to the procedure described by Riant et al. [17]. A round-bottomed flask was loaded with the appropriate amino-alcohol (1equiv.) in 5mL of ethanol. Next, 1equiv of the aldehyde and a few drops of acetic acid were added. The reaction was refluxed overnight. At the end of the reaction, the mixture was concentrated in vacuo. Purification by flash chromatography on silica gel or re-crystallization was carried out if necessary. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In ethanol;Reflux; | General procedure: The metallic precursors and the chiral ligands were obtained according to the procedure described by Riant et al. [17]. A round-bottomed flask was loaded with the appropriate amino-alcohol (1equiv.) in 5mL of ethanol. Next, 1equiv of the aldehyde and a few drops of acetic acid were added. The reaction was refluxed overnight. At the end of the reaction, the mixture was concentrated in vacuo. Purification by flash chromatography on silica gel or re-crystallization was carried out if necessary. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In ethanol at 20℃; for 10h; Reflux; Inert atmosphere; | Synthesis of C2-symmertric chiral shift reagent 2. To a solution of compound 6 (230 mg, 0.5mmol) in ethanol with triethylamine (158 uL, 1.1 mmol) was added (1R, 2S)-1-amino-2-indanol(163 mg, 1.1 mmol) at one time, after stirred in room temperature for 6 h, the reaction mixture was refluxed for another 4 h, a white precipitate was obtained. After the mixture was cooled to room temperature, it was filtered and the residue was washed with ethanol (3 × 5 mL).Compound 2 was obtained as a white solid, 90% yield, (mp > 360 C). 1H NMR (400 MHz,DMSO-d6) δ 8.31 (br, 2H, N5H), 8.13 (d, J 8 Hz, 2H, N7H), 7.27-7.06 (m, 18H), 5.65 (br, 2H),5.59 (br, 2H), 5.41 (br, 2H, OH), 4.51 (s, 2H), 3.10 (d, J 12, 2H), 2.83 (d, J 16 Hz, 2H). 13CNMR (100 MHz, DMSO-d6) δ 182.89, 182.50, 167.54, 167.41, 141.51, 140.53, 138.21, 128.72,127.98, 127.70, 127.18, 126.65, 124.94, 124.06, 72.96, 63.30, 61.11. HRMS Calcd. forC40H34N4O6 Na [M+ Na]+ 689.2376, Found: 689.2364. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate; sodium iodide In acetonitrile at 80℃; for 8h; | 199.5 Step 5 tert-butyl 5-cyclopropyl-2-fluoro-4- ( (1- ( (1R, 2S) -2-hydroxy-2, 3-dihydro-1H-inden-1-yl) piperidin-4-yl) methoxy) benzoate A mixture of tert-butyl 4- (4-bromo-2- (2-bromoethyl) butoxy) -5-cyclopropyl-2-fluorobenzoate (0.84 g, 1.7 mmol) , (1R, 2S) -1-amino-2, 3-dihydro-1H-inden-2-ol (0.253 g, 1.7 mmol) , potassium carbonate (0.47 g, 3.4 mmol) and sodium iodide (0.026 g, 0.17 mmol) in acetonitrile (10 mL) was stirred at 80 for 8 h. The reaction mixture was quenched with brine (40 mL) , extracted with ethyl acetate (10 mL×3) , dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (eluting with 15 ethyl acetate in petroleum ether) to afford the target compound as a white solid (0.712 g, 87) . MS (ESI) : m/z: 482.3 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With copper(l) iodide; copper(ll) bromide In acetonitrile at 60℃; for 0.5h; Microwave irradiation; Sealed tube; | Generalprocedure for the synthesis of 1,4-diheterocycle-2-butynes 4 General procedure: A mixture of aminoalcohol 1 (1.4 mmol), 37%formaldehyde solution (3.2 mmol) 2,and propiolic acid 3 (0.6 mmol) wasdissolved in CH3CN (1.0 mL) applying a microwave vial along with amagnetic stir bar, and then CuI (0.09 mmol) and CuBr2 (0.06 mmol)was added. The reaction vessel was sealed and irradiated in the cavity ofBiotage microwave reactor at a ceiling temperature of 60 °C and a maximum powerof 100 W for 30 min. The resulting reaction mixture was loaded on a silica gelcolumn and ashed with 4-10% EtOAc in hexane to aordthe desired product 4 as a lightyellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With copper(l) iodide; copper(ll) bromide In acetonitrile at 60℃; for 0.5h; Microwave irradiation; Sealed tube; | General procedure for the synthesis of terminal N-propargyl heterocycles5. General procedure: A mixtureof amino alcohol 1 (0.7 mmol), 37%formaldehyde solution (1.6 mmol) 2,and propiolic acid 3 (1.0 mmol) wasdissolved in CH3CN (1.0 mL) applying a microwave vial along with amagnetic stir bar, and then CuI (0.105 mmol) and CuBr2 (0.07 mmol) wasadded. The reaction vessel was sealed and irradiated in the cavity of Biotagemicrowave reactor at a ceiling temperature of 60 °C and a maximum power of 100W for 30 min. The resulting reaction mixture was loaded on a silica gel columnand ashed with 15-40% EtOAc in hexane to aord the desired product 5 as a light yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at -15 - 20℃; Inert atmosphere; | 2.1 3-Hydroxy-N-[(1R,2S)-cis-2-hydroxy-2,3-dihydro-1H-inden-1-yl]naphthalene-2-carboxamide 7 General procedure: 3-Hydroxy-2-naphthoic acid (1.0g, 5.31mmol) was dissolved in dry THF (10mL). The mixture was cooled to -15°C, then N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) (1.53g, 7.965mmol), and HOBt (0.83g, 5.416mmol) were added. A solution of (2S)-2-amino-2-phenylethanol (0.80g, 5.841mmol) in dry THF (5mL) was then introduced by the dropwise addition over a period of 0.5h under an argon atmosphere at the same temperature. After the addition was completed, the mixture was allowed to the warm to room temperature and stirred for an appropriate time (monitored by TLC). When the reaction was completed, the THF was removed under reduced pressure. Water (10mL) was then added. The mixture was extracted with CHCl3 (2×10mL) and dried over anhydrous Na2SO4. Amide 7 was prepared as described above for 1 starting from 3-hydroxy-2-naphthoic acid (1.00g, 5.31mmol), dry THF (5mL), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) (1.52g, 7.96mmol), HOBt (0.83g, 5.42mmol) and (1R,2S)-(+)-cis-1-amino-2-indanol (0.87g, 5.84mmol). The crude product was recrystallized from toluene:ethyl acetate (1/1) mixture to give amide 7 as a yellow solid (1.2g, 73%) yield. Mp: 175.7-178.8°C, [α]D20=+63.0° (c 1, CH3CN). IR (KBr,νmax): 3494, 3331, 3052, 2956, 1645, 1621, 1596, 1401, 1237, 1181, 1086, 1073, 870, 745, 649cm-1, 1H NMR (DMSO-d6): δ (ppm) A part of AB spin system: 2.90 (d, J=16.4, 1H, CHBHA), B part of AB spin system: 3.15 (dd, J=4.8 and 16.4Hz, 1H, CHBHA), 4.56-4.59 (m, 1H, -CH-OH), 5.36 (d, J=4.4Hz, 1H, OH), 5.51 (q, J=5.2Hz, 1H, -NHCH-) 7.18-7.37 (m, 6H, Ar-H), 7.49-7.52 (m, 1H, Ar-H), 7.75 (d, J=8.3Hz, 1H, Ar-H), 7.92 (d, J=8.2Hz, 1H, Ar-H), 8.73 (s, 1H, Ar-H), 9.24 (d, J=8.2Hz, 1H, NH),11.62 (s, 1H, Ar-OH). 13C NMR (DMSO-d6): δ (ppm) 40.41 (-CH2- from DEPT 135 spect.), 57.82 (-CNH-), 72.43 (-COH), 110.98 (Ar-C), 120.67 (Ar-C), 124.11 (Ar-C), 124.79 (Ar-C), 125.40 (Ar-C), 126.10 (Ar-C), 126.88 (Ar-C), 127.43 (Ar-C), 127.87 (Ar-C), 128.56 (Ar-C), 129.35 (Ar-C), 132.03 (Ar-C), 136.27 (Ar-C), 141.29 (Ar-C), 142.70 (Ar-C), 154.54 (Ar-C-OH), 166.58 (C=O). Anal. Calcd for C20H17NO3 (Mw: 319g/mol): C, 75.24; H, 5.33; N, 4.39. Found: C, 75.23; H, 5.31; N, 4.43 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With N-ethyl-N,N-diisopropylamine In butan-1-ol at 100℃; for 72h; | 74.a (a) (1 R,2S)- 1 -(6-Chloro-4, 8-bis(methylamino)pyrimido[5 ,4-dj pyrimidin-2-ylamino)-- indan-2-ol (122) A mixture of 2,6-dichloro-N4,N8-dimethyl-pyrimido[5,4-dj pyrimidine-4, 8- diamine (88) (250 mg, 0.96 mmol), (1R,25)-1-amino-indan-2-ol (215 mg, 1.44 mmol) and N,N-diisopropylethylamine (166 tL, 0.96 mmol) in n-butanol (3 mL) was heated at 100°C for 72 h. The reaction mixture was cooled, the precipitate was filtered, washed with water (2 x 10 mL) and dried over solid P205 to afford (1R,2S)-1-(6-chloro-4,8-bis(methylamino)pyrimido [5,4-djpyrimidin-2-ylamino)- indan-2-ol (122) (260 mg, 73% yield). 300 MI-Tz ‘H NMR (CDC13, ppm): 7.38-7.32 (1H, m) 7.32-7.18 (3H, m) 6.72-6.56 (2H, m) 5.58-5.45 (2H, m) 4.81-4.73 (1H, m) 3.23 (1H, dd, J=16.5, 5.3 Hz) 3.14 (3H, d, J5.2 Hz) 3.06 (3H, d, J5.1 Hz) 3.04 (1H, dd, J=16.5, 2.5 Hz) 2.56 (1H, br s). ESI-MS (m/z): 372, 374 [M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate In 1-methyl-pyrrolidin-2-one; acetonitrile at 50 - 60℃; for 8h; | 4 Preparation of N-benzyl-(1R,2S)-1-amino-2-indanol (1.0 equiv.) Of (1R, 2S) -1-amino-2-indene alcohol was dissolved in a mixed solvent of 50 ml of NMP and acetonitrile (1: 1)Add 5 g of potassium carbonate,Stir,Heating up to 50 ~ 60 ,A solution of 1.0 equivalents of benzyl chloride in acetonitrile was added dropwise 10 ml,After dripping,Continue to heat the reaction 8h,after the end,filter,Concentrated under reduced pressure,Ethyl acetate to recrystallize,A pale yellow solid of 24.83 g,The yield was 86.0% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; isopropyl alcohol; at 60℃; | Crude (S) -3-cyclohexane-1-carboxylic acid / (1R, 2S) -1-amino-3-cyclohexane-1-carboxylic acid (4.55 g), (1R, 2S) -1-amino-2-indanol (4.30 g) was added to water containing 2-propanol (45 mL), heated to 60 C. To dissolve the precipitate. The reaction solution was cooled to 50 C. and stirred for 2 hours after crystallization. It was gradually cooled to room temperature at 5 C / h and stirred for 12 hours. The precipitate was collected by filtration, washed with 2-propanol (10 mL), and dried under reduced pressure at 40 C. to obtain the title compound (5.05 g, 50.9%, 26.5% ee) as a white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20℃; for 2h; | To a methanolic solution (10 mL) of <strong>[84501-28-0]2,6-diformyl-4-tert-butylphenol</strong> (0.309 g, 1.5 mmol) was added amino-indanol (0.447 g, 3 mmol) and the solution was stirred at room temperature for 2 h. After 2 h was added a MeOH solution (10 mL) of Na2CO3 (0.105 g, 1 mmol) and of Ni(ClO4)2·6H2O (1.097 g, 3 mmol), followed by stirring for 3 h at room temperature in air. The resulting solution was syringe filtered. Pale green crystals of complex 3 were obtained by slow diffusion of diethyl ether into the methanolic reaction mixture over a period of 3 days (yield 0.564 g, 31%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In dichloromethane at 0 - 20℃; | 2.2 Example 2 In the second step, (1R,2S)-guanidinoethanol (2.98g, 20mmol) and triethylamine (3.03g, 30mmol) were added to 25ml of dichloromethane, and the temperature was controlled at 0-5°C. Trimethylsilyl sulfonate (24 mmol), stirred at room temperature after stirring, TLC detection reactionAfter completion, add water to quench, wash with sodium bicarbonate solution, wash with saturated saline, and dry (1R, 2S)-prolinol trimethylsilylether with organic layer.4.0g, yield 90% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 140℃; for 8h; | 2.2 Synthesis ofManganese(III) 5-[4-N-(2-hydroxy-indan-1-yl)benzamide],10,15,20-tris(4-carboxy phenyl)porphyrinchloride [Mn(TCPP-Ind)Cl] Following the methodology reported by Kobayashi [30], themetallation of H2TCPPwith MnCl2provided Mn(TCPP)Cl.For adding the chiral substituent, the solution of (1R,2S)-(+)-cis-1-amino-2-indanol (8.30mg, 0.056mmol) and dicyclohexylcarbodiimide(DCHC) (11.0mg, 0.056mmol) in10mL of N,N-dimethylformamide (DMF) was added dropwiseto the solution of Mn(TCPP)Cl (0.05g, 0.056mmol)in DMF (5mL). The mixture was refluxed at 140°C for8h. Following the removal of the solvent under vacuum,the precipitate dissolved in 20mL of 0.1M NaOH solutionand precipitated by adding 1M HCl solution. The productwas recrystallized from ethanol. The pure [Mn(TCPP-Ind)Cl] was dried at room temperature. Yield 72% (0.041g).UV-Vis in ethanol: λmax (log ε , dm3mol-1 cm-1): 466(4.69), 565 (3.82), 599 (3.67). FT-IR (KBr, cm-1): 3424(s, br, O-H), 2926 (S), 2853 (m), 1712 (vs, -CO2), 1629(s, N-C=O), 1608 (m, C=C), 1541 (m, N-H). Anal. Calcdfor C69H67ClMnN9O13([Mn(TCPP-Ind)Cl]·4DMF·H2O): C,62.75; H, 5.11; N, 9.54. Found C, 62.60; H, 6.59; N, 9.53. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With dmap; triethylamine In dichloromethane at 20℃; for 16h; Cooling with ice; | 33 Example 33 Preparation of (1R,2S)-1-acetamido-2-indanyl acetate 1m 3 g of (1R,2S)-1-amino-2-indanol and 8 mL of triethylamine were sequentially added to a 200 mL round bottom flask.20 mg of dimethylaminopyridine, 100 mL of dichloromethane, and 5 mL of acetic anhydride were slowly added dropwise while stirring in an ice bath.After the completion of the dropwise addition, the ice bath was removed, and the system was stirred at normal temperature for 16 hours.The reaction mixture was washed with water, aq.Finally separated by column chromatography (eluent: ethyl acetate)The product was obtained in 1 m, and the isolated yield was 73%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | In acetonitrile at 20℃; | S3 Example S3: (3S)-3-f4-[(2, 3-dimethylbut-2-en- 1 -yl)oxy]phenyllhex-4-ynoic acid, salt with (1R,2S)-1 -amino-2-indanol (3S)-3-f4-[(2,3-Dimethylbut-2-en-1 -yl)oxy]phenyllhex-4-ynoic acid, obtained in Example F33 as an oil under normal conditions (300 mg, 1 .05 mmol), was dissolved in acetonitrile (10 ml) and warm solution of (1R,2S)-1-amino-2-indanol (150 mg, 0.985 mmol) in 5 ml of acetonitrile was added while stirring. After 5 minutes ofstirring, as the reaction mixture reached room temperature, a solid was formed that was filtered-off on a glass frit, washed with cold acetonitrile and n-pentane, and dried under reduced pressure. The title salt was obtained as colorless crystals (252 mg 55% yield) having melting point in the range of 137.8 - 139.1°C (with decomposition). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With 1,4-diaza-bicyclo[2.2.2]octane; acriflavine In acetonitrile for 38h; Inert atmosphere; | 16 Example 16 In the 5 mL reaction flask, the enol silyl ether compound 1a (0.6 mmol),Perfluorobutane iodide 2a (0.9 mmol), amino alcohol compound 3b (0.3 mmol),Triethylenediamine (DABCO) (134.5mg, 1.2mmol)And acriflavine (0.2 mg, 0.0009 mmol) was stirred and mixed in acetonitrile (2.0 mL).After being replaced by N2 for 3 times, it was placed under a 4.5 watt white light-emitting diode and stirred for 38 hours. After the reaction was completed by TLC, the reaction solution was concentrated.Purification by silica gel column chromatography (ethyl acetate / petroleum ether as mobile phase) gave sample 4q,The yield was 59%. Dr is greater than 20:1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In toluene for 21h; Reflux; Dean-Stark; | 4.1.2. General procedure for cyclocondensation reactions General procedure: To a suspension of cis-1-aminoindan-2-ol (1.0 eq.) in toluene (0.13 M) was added the appropriate oxocarboxylic acid (1.0-1.2eq.). The mixture was heated at reflux for 10-24 h under Dean-Stark apparatus, until total consumption of the starting aminoalcohol. The reaction mixture was concentrated in vacuo and the residue obtained was dissolved in EtOAc. The organic phase was washed with saturated aqueous solution of NaHCO3 and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography (elution with AcOEtand n-hexane). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In toluene for 21h; Reflux; Dean-Stark; | 4.1.2. General procedure for cyclocondensation reactions General procedure: To a suspension of cis-1-aminoindan-2-ol (1.0 eq.) in toluene (0.13 M) was added the appropriate oxocarboxylic acid (1.0-1.2eq.). The mixture was heated at reflux for 10-24 h under Dean-Stark apparatus, until total consumption of the starting aminoalcohol. The reaction mixture was concentrated in vacuo and the residue obtained was dissolved in EtOAc. The organic phase was washed with saturated aqueous solution of NaHCO3 and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography (elution with AcOEtand n-hexane). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In toluene; for 17h;Reflux; Dean-Stark; | General procedure: To a suspension of cis-1-aminoindan-2-ol (1.0 eq.) in toluene (0.13 M) was added the appropriate oxocarboxylic acid (1.0-1.2eq.). The mixture was heated at reflux for 10-24 h under Dean-Stark apparatus, until total consumption of the starting aminoalcohol. The reaction mixture was concentrated in vacuo and the residue obtained was dissolved in EtOAc. The organic phase was washed with saturated aqueous solution of NaHCO3 and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography (elution with AcOEtand n-hexane). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In toluene; for 20.0h;Reflux; Dean-Stark; | General procedure: To a suspension of cis-1-aminoindan-2-ol (1.0 eq.) in toluene (0.13 M) was added the appropriate oxocarboxylic acid (1.0-1.2eq.). The mixture was heated at reflux for 10-24 h under Dean-Stark apparatus, until total consumption of the starting aminoalcohol. The reaction mixture was concentrated in vacuo and the residue obtained was dissolved in EtOAc. The organic phase was washed with saturated aqueous solution of NaHCO3 and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography (elution with AcOEtand n-hexane). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In toluene at 20℃; for 24h; | General procedure for preparation of bicyclic azasugars with glycosidic heteroatom General procedure: To a stirred solution of D-ribose tosylate 5 (200mg, 0.58mmol) in toluene (5mL) was added amino alcohol or diamine (1.16mmol). The resultant mixture was stirred at room temperature for 24h, until the reaction was completed as indicated by TLC. The reaction mixture was purified by column chromatography on silica gel (10:1-2:1 petroleum ether/ethyl acetate) to give bicyclic azasugars. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With zinc(II) chloride In chlorobenzene for 24h; Reflux; | General procedure for the synthesisof 2-(o-aminophenyl)oxazolines 8a-8h General procedure: An oven-dried two-necked flask was washed with argonand charged with 118 mg 2-aminobenzonitrile (1 mmol) or136 mg 2-amino-5-fluorobenzonitrile (1 mmol) or 163 mg2-amino-5-nitrobenzonitrile (1 mmol), the appropriateamino alcohol (1.5 mmol), 405 mg freshly flame dried ZnCl2(3 mmol), and 10 cm3anhydrous chlorobenzene. The mixturewas stirred under reflux for 24 h. The solvent was thenremoved under reduced pressure and the residue was stirredwith 30% NaOH for 0.5 h. The product was extracted withethyl ether and purified by flash column chromatographyon silica gel. 2-[(4S)-4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl]aniline(8a) Compound 8a was prepared from 118 mg 2-aminobenzonitrile(7a, 1 mmol) and 205 mg S-phenylglycinol(6a, 1.5 mmol). White crystals; yield 203 mg (85%). All thephysical and spectroscopic data are with agreement with theones published in Ref. [29]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With [2,2]bipyridinyl; copper(I) bromide dimethylsulfide complex; Cs2CO3 In 1,4-dioxane at 110℃; for 15h; Inert atmosphere; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With [2,2]bipyridinyl; copper(I) bromide dimethylsulfide complex; Cs2CO3 In 1,4-dioxane at 110℃; for 15h; Inert atmosphere; Autoclave; |
A106384[ 126456-43-7 ]
(1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol
Reason: Optical isomers
[ 103028-83-7 ]
1-Amino-1,2,3,4-tetrahydronaphthalen-2-ol hydrochloride
Similarity: 0.93
[ 255060-27-6 ]
(1R,2R)-1-Amino-1-phenylpropan-2-ol hydrochloride
Similarity: 0.93
[ 88784-91-2 ]
(1R,2S)-1-Amino-1-phenylpropan-2-ol hydrochloride
Similarity: 0.93
[ 926292-63-9 ]
(R)-2-Amino-2-(m-tolyl)ethanol
Similarity: 0.85
[ 2095772-93-1 ]
(S)-2-Amino-2-(m-tolyl)ethanol hydrochloride
Similarity: 0.83
[ 103028-83-7 ]
1-Amino-1,2,3,4-tetrahydronaphthalen-2-ol hydrochloride
Similarity: 0.93
[ 255060-27-6 ]
(1R,2R)-1-Amino-1-phenylpropan-2-ol hydrochloride
Similarity: 0.93
[ 88784-91-2 ]
(1R,2S)-1-Amino-1-phenylpropan-2-ol hydrochloride
Similarity: 0.93
[ 926292-63-9 ]
(R)-2-Amino-2-(m-tolyl)ethanol
Similarity: 0.85
[ 2095772-93-1 ]
(S)-2-Amino-2-(m-tolyl)ethanol hydrochloride
Similarity: 0.83
[ 103028-83-7 ]
1-Amino-1,2,3,4-tetrahydronaphthalen-2-ol hydrochloride
Similarity: 0.93
[ 255060-27-6 ]
(1R,2R)-1-Amino-1-phenylpropan-2-ol hydrochloride
Similarity: 0.93
[ 88784-91-2 ]
(1R,2S)-1-Amino-1-phenylpropan-2-ol hydrochloride
Similarity: 0.93
[ 926292-63-9 ]
(R)-2-Amino-2-(m-tolyl)ethanol
Similarity: 0.85
[ 2095772-93-1 ]
(S)-2-Amino-2-(m-tolyl)ethanol hydrochloride
Similarity: 0.83
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :