Structure of 267410-86-6
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CAS No. : | 267410-86-6 |
Formula : | C18H17NO3 |
M.W : | 295.33 |
SMILES Code : | O=C(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)NCCC=O |
MDL No. : | MFCD12031772 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330 |
* 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 |
---|---|---|
80% | With hydrogenchloride; water; sodium cyanoborohydride; In N,N-dimethyl-formamide; at 20℃; for 16h; | N, N-Oi-[N- (9-fluorenylmethoxycarbonyl) -3-aminopropyl } -AmB:; To a solution of N- ( 9-fluorenylmethoxycarbonyl) -3-aminopropanal (150 mg, 0.510 mmol) and AmB (Ia) (157 mg, 0.170 mmol) in DMF (3.00 mL) was added NaBH3CN (32.0 mg, 0.510 mmol) followed by a drop of cone. HCl. After 16 h at room temperature, Amberlite IRA-743 (300 mg) was added and the mixture was stirred for an hour. After filtration, the solution was concentrated down and added dropwise to diethyl ether (250 mL) . The yellow precipitate was filtered and purified by flash chromatography (10-6-1 CHCl3- MeOH-H2O) providing the desired compound as a yellow solid (200 mg, 80%). Rf 0.70 (10-6-1 CHCl3-MeOH-H2O), 1H NMR (500 MHz, DMSO- d6) delta 7.87 (d, J = 8 Hz, 4H), 7.68 (d, J = 8 Hz, 4H), 7.40 (t, J = 8 Hz, 4H), 7.31 (t, J = 8 Hz, 4H), 6.46-6.06 (m, 12H), 5.96 (dd, J = 14, 8 Hz, IH), 5.84 (s, IH), 5.44 (dd, J = 15, 10 Hz, IH), 5.33 (s, IH), 5.21 (s (br) , IH), 4.79-4.60 (m, 4H), 4.43- 4.19 (m, 10H), 4.07-3.97 (m, 2H), 3.81 (s, IH), 3.55-3.41 (m, 3H), 3.31 (s (br) , OH), 3.13-3.02 (m, 6H), 2.77 (s, IH), 2.64 (s, IH), 2.28 (s, IH), 2.17 (d, J = 6 Hz, IH), 1.93-1.24 (m, 18H), 1.19 (d, J = 6 Hz, 3H), 1.11 (d, J = 7 Hz, 3H), 1.04 (d, J = 6 Hz, 3H), 0.92 (d, J = I Hz, 3H), 13C NMR (125 MHz, DMSO-d6) delta177.6, 170.5, 162.2, 156.0, 143.9, 142.5, 140.6, 139.3, 137.3,136.7, 133.8, 133.6, 133.4, 133.1, 132.4, 132.3, 132.1, 131.9, 131.8, 131.7, 131.2, 128.8, 127.5, 127.2, 127.0, 125.1, 121.3,119.9, 101.2, 97.1, 77.1, 77.0, 73.9, 73.5, 69.5, 69.1, 68.8, 67.8, 67.5, 66.1, 65.2, 64.8, 58.2, 48.3, 46.7, 44.8, 44.6, 44.2, 42.0, 41.9, 38.4, 35.7, 35.0, 30.7, 28.9, 28.5, 18.4, <n="59"/>18.2, 16.9, 15.1, 12.0; MALDI-TOF calcd for C87Hi07N3O2I [M+Na+] 1504.7295. Found: 1504.7289. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis of N- ( 9-fluorenylmethoxycarbonyl) -3-aminopropyl-AmB:; To a solution of N- (9-fluorenylmethoxycarbonyl) -3-aminopropanal(More, J. D. and Finney, N. S. Org. Lett. 2002, 4, 3001) (59.0 mg, 0.200 mmol) in DMF (3.00 mL) and MeOH (3.00 mL) was addedAmB (1) (216 mg, 0.200 mmol). After 3 h, NaBH3CN (40.0 mg, 0.600 mmol) was added to the mixture. After 16 h at room temperature, <n="72"/>Amberlite IRA-743 (500 mg) was added and the mixture was stirred for an hour. After filtration, the solution was concentrated down and added dropwise to diethyl ether (250 mL) . The yellow precipitate was filtered and purified by flash chromatography (40-8-1 CHCl3-MeOH-H2theta) providing the desired compound as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; sodium sulfate; In chloroform; toluene; at 20℃; under 760.051 Torr;Inert atmosphere; | Step 3: p-Toluenesulfonic acid (30.6 g, 177.9 mmol) and Na2SO4 (2.528 kg, 17.8 mol) were added to a mixture of (9H-fluoren-9-yl)methyl(3-oxopropyl)carbamate (525 g, 1.778 mol) in toluene (6 L) and CHCl3 (1.8 L) at RT. To the mixture was added tert-butyl(1,3-dihydroxypropan-2-yl)carbamate (251.8 g, 2.133 mol). The reaction mixture was stirred overnight at RT and floccus solid formed. The pH of the reaction mixture was adjusted to 7 by adding anhydrous Na2CO3 and the suspension liquid was decanted from Na2SO4. The floccus solid in the suspension liquid was collected by filtration and washed with DCM (2 L). The solid obtained (100 g) was retrospectively identified as {(2R,5R)-2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-[1,3]dioxan-5-yl}-carbamic acid tert-butyl ester (anti isomer). LCMS (ESI): m/z=491 [M+23]+. The filtrates were combined and H2O (2 L) and DCM (2 L) were added. The organic phase was separated and the aqueous phase was extracted with DCM (3×500 mL). The combined organic layers were washed with brine (1 L) and dried (Na2SO4), filtered and evaporated. The residue was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (EA:hexane=1:8 to 1:4) to afford a second crop of product (390 g) as a brown oil. This crop was retrospectively identified as-9:1 mixture of {(2S,5S)-2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-[1,3]dioxan-5-yl}carbamic acid tert-butyl ester (syn isomer) and {(2R,5R)-2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-[1,3]dioxan-5-yl}-carbamic acid tert-butyl ester (anti isomer). LCMS (ESI): m/z=491 [M+23]+. | |
With toluene-4-sulfonic acid; sodium sulfate; In chloroform; toluene; at 20℃; under 760.051 Torr;Inert atmosphere; | Step 3: p-Toluenesulfonic acid (30.6 g, 177.9 mmol) and Na2SO4 (2.528 kg, 17.8 mol) were added to a mixture of (9H-fluoren-9-yl)methyl(3-oxopropyl)carbamate (525 g, 1.778 mol) in toluene (6 L) and CHCl3 (1.8 L) at RT. To the mixture was added <strong>[125414-41-7]tert-butyl (1,3-dihydroxypropan-2-yl)carbamate</strong> (251.8 g, 2.133 mol). The reaction mixture was stirred overnight at RT and floccus solid formed. The pH of the reaction mixture was adjusted to 7 by adding anhydrous Na2CO3 and the suspension liquid was decanted from Na2SO4. The floccus solid in the suspension liquid was collected by filtration and washed with DCM (2 L). The solid obtained (100 g) was retrospectively identified as {(2R,5R)-2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-[1,3]dioxan-5-yl}-carbamic acid tert-butyl ester (anti isomer). LCMS (ESI): m/z=491 [M+23]+. The filtrates were combined and H2O (2 L) and DCM (2 L) were added. The organic phase was separated and the aqueous phase was extracted with DCM (3×500 mL). The combined organic layers were washed with brine (1 L) and dried (Na2SO4), filtered and evaporated. The residue was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (EA:hexane=1:8 to 1:4) to afford a second crop of product (390 g) as a brown oil. This crop was retrospectively identified as 9:1 mixture of {(2S,5S)-2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-[1,3]dioxan-5-yl}carbamic acid tert-butyl ester (syn isomer) and {(2R,5R)-2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-[1,3]dioxan-5-yl}-carbamic acid tert-butyl ester (anti isomer). LCMS (ESI): m/z=491 [M+23]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of Amphotericin B in DMF and 1V-(9- fiuorenyimethoxycarbonyi)3aminopropanai (3 eq.) is treated with NaBH3CN (3 eq.) followed by a drop of concentrated HC1 and stirred until completion at which point amberlite 1RA-743 resin is added and stirred for 1 hour. The resin is filtered, and the reaction mixture is concentrated under vacuum and then diluted with Ft20. The resulting crude product is filtered off and purited by column chromatography to provide ht7. |