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[ CAS No. 361442-00-4 ] {[proInfo.proName]}

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Chemical Structure| 361442-00-4
Chemical Structure| 361442-00-4
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Product Details of [ 361442-00-4 ]

CAS No. :361442-00-4 MDL No. :MFCD16660445
Formula : C17H27NO5 Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W : 325.40 Pubchem ID :-
Synonyms :

Calculated chemistry of [ 361442-00-4 ]

Physicochemical Properties

Num. heavy atoms : 23
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.88
Num. rotatable bonds : 6
Num. H-bond acceptors : 5.0
Num. H-bond donors : 3.0
Molar Refractivity : 84.72
TPSA : 95.86 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.84 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.27
Log Po/w (XLOGP3) : 2.04
Log Po/w (WLOGP) : 2.3
Log Po/w (MLOGP) : 1.78
Log Po/w (SILICOS-IT) : 1.5
Consensus Log Po/w : 1.98

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -2.75
Solubility : 0.583 mg/ml ; 0.00179 mol/l
Class : Soluble
Log S (Ali) : -3.68
Solubility : 0.0678 mg/ml ; 0.000208 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.94
Solubility : 3.74 mg/ml ; 0.0115 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 5.22

Safety of [ 361442-00-4 ]

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:

Application In Synthesis of [ 361442-00-4 ]

* 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.

  • Downstream synthetic route of [ 361442-00-4 ]

[ 361442-00-4 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 361441-97-6 ]
  • [ 361442-00-4 ]
  • [ 681282-72-4 ]
YieldReaction ConditionsOperation in experiment
51%; 17% With potassium hydroxide; potassium permanganate; In water; at 60 - 90℃; for 1.5h; A SOLUTION OF KMN04 (337 mg, 2.13 mmol, 1.1 equiv) in 2percent aq KOH (6 mL) was heated to 60°C and Step 7 compound in general method G (600 mg, 1.94 mmol, 1 equiv) was added in portions, and heating increased to 90°C. After 1.5 h, the reaction was cooled to 0°C, EtOAc (50 mL) was added, and the mixture was carefully acidified to pH 3 with 1 N HCI. The layers were separated and the aqueous was extracted with EtOAc (50 mL). The combined organic extracts were washed with brine, dried over NA2SO4, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (3. 8x15 cm) with 2percent (200 mL), 3percent (200 mL), 4percent (200 mL), and 5percent (500 mL) MEOH/CH2CI2 + 0.5percent HOAc. After isolation of the product, the material was chased with hexanes to afford a white solid (324 mg, 51 percent) : MS M/E 326 (m+H) +. Refer to the procedure of Example 1, Step 8 that generates HYDROXYADAMANTYL-N-TERT- butyloxycarbonyl-L-glycine. During the reaction, the DIOI is formed as a lower Rf minor product. Slightly longer reaction times (up to 90 min) gave up to 17percent of the diol in addition to the Example 1, Step 8 compound. With the procedure identical in every other respect, the diol is obtained as a white solid, after chasing with hexanes, by flushing the column with 15percent MEOH-CH2CI2-0. 5percent HOAC. 1H NMR (500 MHz, CD30D) 1.41-1. 73 (m, 21 H), 2.29 (BRS, 1H), 3.95 (s, 1H). 13C NMR (125 MHz, CD30D) 174.2, 157.9, 80.6, 71.0, 70.9, 63.1, 52.5, 49.6, 48.3, 46.3, 43.9, 41.8, 37.5, 31. 8, 28.7.
  • 2
  • [ 361442-00-4 ]
  • (2S,4S,5S)-4,5-methano-L-proline carboxylamide trifluoroacetate [ No CAS ]
  • [ 361442-01-5 ]
YieldReaction ConditionsOperation in experiment
85% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; The Step 1 compound (404 mg, 1.24 mmol, 1 equiv) was dissolved in anhydrous DMF (10 mL) under argon and cooled to 0°C. The following were added in order: Example 6 Step 3 salt (328 mg, 1.37 mmol, 1.1 equiv), HOBT (520 mg, 3.85 mmol, 3.1 equiv), EDAC (510 mg, 2.61 mmol, 2.1 equiv), and TEA (0.54 mL, 3.85 mmol, 3.1 equiv). The reaction mixture was allowed to warm to rt overnight and the DMF removed by rotary evaporation (pump). The remainder was dried further under vacuum. The residue was dissolved in EtOAc (100 mL), washed with satd aq NaHCO3 (50 mL) and satd aq NaCl (25 mL), dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation. The product was purified flash column chromatography on silica gel (3.8x15 cm) with a gradient of 6percent (200 mL), 7percent (200 mL), and 8percent (500 mL) MeOH/CH2Cl2 to give the product as a white solid (460 mg, 1.06 mmol, 85percent): MS m/e 434 (m+H)+.
  • 3
  • [ 361442-00-4 ]
  • [ 24426-40-2 ]
  • [(cyanomethyl-ethyl-carbamoyl)-(3-hydroxy-adamantan-1-yl)-methyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
  • 4
  • [ 361442-00-4 ]
  • [ 5616-32-0 ]
  • [(cyanomethyl-methyl-carbamoyl)-(3-hydroxy-adamantan-1-yl)-methyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
  • 5
  • (αS)-α-amino-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid [ No CAS ]
  • [ 24424-99-5 ]
  • [ 361442-00-4 ]
YieldReaction ConditionsOperation in experiment
98% With potassium carbonate; In tetrahydrofuran; at 20℃; for 12h; 1Ommol of 3-hydroxyl-1-adamantyl-D-glycine, 0.6mmol Potassium carbonate, 12mmol of di-tert-butyl dicarbonate and 30mL of tetrahydrofuran are added into the reaction flask, stir and mixed the mixture and carry on reaction for 12 hours at room temperature. The solvent is distilled off under reduced pressure, to the residue added 50mL petroleum ether, and then by using 5M HCl adjust the pH value at 1, a white solid has been precipitation, suction filtration, drying under reduced pressure and then obtain a compound of formula (I), yield 98percent.
88% BOC-protection Di-tert-butyl dicarbonate (1.022kg ; 4. 68MOL) was added to a portion of the solution of (AS)-A-AMINO-3-HYDROXYTRICYCLO [3.3. 1. 137] DECANE-L-ACETIC acid (Formula V) (477.5g ; 2. 12mol). This mixture was stirred at ambient temperature, with pH adjusted to and maintained at 10 with a pH stat titrator using ION NAOH. The reaction was complete 4hrs after BOC20 addition when there was less than 1.0percent starting material remaining. The pH of the mixture was adjusted TO-8 with 35percent H2SO4 and i-PrOAc (5. 0L) was added to the mixture. The pH of the mixture was then adjusted to 2.0 with 35percent H2SO4 and maintained at this pH for 5-10 min. Dicalite (250g) was added; the mixture was stirred FOR ~LOMIN, and then filtered through a pad of Dicalite (250g) on filter paper in a Buchner funnel. The Dicalite pad was further washed with 2.5L i- PrOAc. The filtrate was adjusted to pH 8 with ION NaOH. After settling for LHR, the organic layer including interface was discarded. To the aqueous layer, i-PrOAc (7.5L) was added. The mixture was acidified with 35percent H2SO4 to PH-2, and then heated to and maintained AT-40C for 4 hours with mild stirring. The layers were separated and the organic extract was saved. The aqueous layer with interface was extracted with i-PrOAc (3.75L) and the layers were again separated after 2hrs at 40C. The aqueous layer with interface was extracted again with i-PrOAc (3.75L) and the layers were separated after 2hrs at 40C. The combined organic extracts (-15L) were concentrated by distillation to -4. 5L. To this solution, heptane (-IOL) was then added over 10-15MIN while the temperature was maintained at-82-89C. The reactor jacket temperature was set to 70C and maintained at this temperature for 1 HR. Crystallization occurred shortly after cooling. The reactor jacket temperature was then set at 40C and maintained at this temperature for 30 min. The suspension was cooled down to ambient temperature, and then further cooled to 0-5C. After one hour of stirring at 0-5C, the product was filtered. The product was washed with heptane (2.5L), then dried in vacuo at 40C to give 607. Og (88percent yield) of (AS)-A- [ [ (1, 1-DIMETHYLETHOXY) carbonyl] amino]-3- hydroxytricyclo [3.3. 1. 137] DECANE-L-ACETIC acid (Formula VI).
88% With sodium hydroxide; In Isopropyl acetate; at 20℃; for 4h;pH 10;Large scale; Di-tert-butyl dicarbonate (1.022kg; 4.68mol) was added to a portion of the solution of (alphaS)-alpha-amino-3-hydroxytricyclo[3.3.1.13,7] decane-1-acetic acid (Formula 2) (477.5g; 2.12mol). This mixture was stirred at ambient temperature, with pH adjusted to and maintained at 10 with a pH stat titrator using 10N NaOH. The reaction was complete 4hrs after Boc2O addition when there was less than 1.0percent starting material remaining. The pH of the mixture was adjusted to ?8 with 35percent H2SO4 and i-PrOAc (5.0L) was added to the mixture. The pH of the mixture was then adjusted to 2.0 with 35percent H2SO4 and maintained at this pH for 5-10 min. Dicalite (250g) was added; the mixture was stirred for ?10min, and then filtered through a pad of Dicalite (250g) on filter paper in a Buchner funnel. The Dicalite pad was further washed with 2.5L i-PrOAc. The filtrate was adjusted to pH 8 with 10N NaOH. After settling for 1hr, the organic layer including interface was discarded. To the aqueous layer, i-PrOAc (7.5L) was added. The mixture was acidified with 35percent H2SO4 to pH?2, and then heated to and maintained at ?40°C for 4 hours with mild stirring. The layers were separated and the organic extract was saved. The aqueous layer with interface was extracted with i-PrOAc (3.75L) and the layers were again separated after 2hrs at 40°C. The aqueous layer with interface was extracted again with i-PrOAc (3.75L) and the layers were separated after 2hrs at 40°C. The combined organic extracts (?15L) were concentrated by distillation to ?4.5L. To this solution, heptane (?10L) was then added over 10-15min while the temperature was maintained at ?82-89°C. The reactor jacket temperature was set to 70°C and maintained at this temperature for 1hr. Crystallization occurred shortly after cooling. The reactor jacket temperature was then set at 40°C and maintained at this temperature for 30 min. The suspension was cooled down to ambient temperature, and then further cooled to 0-5°C. After one hour of stirring at 0-5°C, the product was filtered. The product was washed with heptane (2.5L), then dried in vacuo at 40°C to give 607.0g (88percent yield) of (alphaS)-alpha-[[(1,1-dimethylethoxy)carbonyl)amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid (Formula 3).
(
15.6 g With sodium hydroxide; at 25 - 30℃; for 5h; In a 250 ml four-necked reaction flask was added 28 ml of concentrated sulfuric acid,Ice water cooled to 10 oC,20.1 g of the product (aS) -a-adamantane-glycine (formula IV) obtained in Example 5 and 13.3 g of nitric acid (65percent) were added successively,Throughout the process,Control the temperature below 25 oC,After completion of the reaction, the reaction was carried out at room temperature for 4.5 to 5 hours.The reaction solution was poured into 400 ml of ice water,Stir for 30 min.DCM extraction,Layered,Combined organic phase,To the aqueous phase was added 350 ml (10 N) NaOH,Control the temperature below 40oC,Adjust the pH between 8 ~ 9,Then 25.2 g of Boc2O was added,And then slowly added 50 ml (10 N) NaOH,Reaction at 25-30 ° C for 5 hours.After the reaction is complete,Extracted with 200 ml of ether,Stirring for 30min,Layered,The aqueous phase was adjusted to pH 1-2 with 7.5 ml of concentrated sulfuric acid.MTBE extraction reaction solution,Combined organic phase,The organic phase was washed with 100 ml of water,After drying anhydrous sodium sulfate,Add 1.0 activated carbon for 2 h.filter,The filtrate was washed with DCM,The mother liquor was concentrated at 45 ° C to give crude (aS) -a - [[(1,1-dimethylethoxy) carboxy] -amino] -1- (3-hydroxyadamantane).To the crude product was added 100 ml of toluene,25-30oC under stirring to the foam-like solid all dissolved,Heated to 110oC, reflux stirring 20-30min,Cool to room temperature.filter,The solid was washed with 15 ml of toluene,Dried at 55 ° C to give 16.8 g of a white powder.The solid was then beaten with 100 ml of water,Filtered and dried to give 15.6 gWhite powder products(aS) -a- [[(1,1-dimethylethoxy) carboxy] -amino] -1- (3-hydroxyadamantane) -acetic acid (Formula I).

  • 6
  • [ 361442-00-4 ]
  • 2-amino-<i>N</i>-cyanomethyl-2-(3-hydroxy-adamantan-1-yl)-<i>N</i>-methyl-acetamide [ No CAS ]
  • 7
  • [ 361442-00-4 ]
  • 2-amino-<i>N</i>-cyanomethyl-<i>N</i>-ethyl-2-(3-hydroxy-adamantan-1-yl)-acetamide [ No CAS ]
  • 8
  • [ 361442-00-4 ]
  • [(S)-2-((1S,3S,5S)-3-Cyano-2-aza-bicyclo[3.1.0]hex-2-yl)-1-(3-fluoro-adamantan-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester [ No CAS ]
  • 11
  • [ 361442-00-4 ]
  • (S)-3-fluoroadamantylglycine-L-cis-4,5-methanoprolinenitrile TFA salt [ No CAS ]
  • 14
  • (R)-N-((S)-(adamantan-1-yl)(carboxy)methyl)-2-hydroxy-1-phenylethan-1-ammonium chloride [ No CAS ]
  • [ 361442-00-4 ]
  • 20
  • [ 361442-00-4 ]
  • [ 280-57-9 ]
  • [ 709031-42-5 ]
YieldReaction ConditionsOperation in experiment
79% In Isopropyl acetate; water; ethyl acetate; at 20℃; Formula VIA (DABCO Salt) 1, 4-DIAZABICYCLO [2.2. 2] octane (DABCO) (15G ; 125.1 mmole) was charged into a solution of ca. 30g (135 mmole) of Example 36 Formula VI acid in 300 ml of isopropyl acetate. Ethyl acetate (150 mL) was charged into the above reaction mixture (volume ratio of ethyl acetate: isopropyl acetate (150 mL/300 mL) ). The reaction mixture was seeded with Formula VIA DABCO salt (200 mg). The reaction mixture was stirred vigorously at room temperature. Water (5 mL) was slowly charged to the reaction mixture and the reaction mixture stirred vigorously at room temperature to induce crystal formation after 15-20 minutes. The reaction mixture was stirred for 16 hours at room temperature and the reaction product was filtered in a Buchner funnel. The solids were washed with ethyl acetate at room temperature and dried at 50C in vacuo to give 47g (79percent) of the Formula VIA DABCO salt.
  • 21
  • [ 361442-00-4 ]
  • [ 841302-37-2 ]
  • [ 841302-55-4 ]
  • [ 841302-42-9 ]
YieldReaction ConditionsOperation in experiment
27.4%; 40.6% With 4-methyl-morpholine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; In dichloromethane; at 20℃; for 20h; Method A from Example 3, Step 4 compound: To a mixture of the Example 1, Step 8 acid (156.7 mg, 0.48 MMOL), the Step 4 amine (60 mg, 0.51 mmol, 1. 06 equiv) and PYBOP (456 mg, 0.88 mmol, 1.83 equiv) in CH2CI2 (4.5 mL) was added N- methylmorpholine (0.16 mL, 1.5 mmol, 3.1 equiv) and the mixtue was stirred at rt for 20 h. The reaction was then quenched with 5% KHS04 (4.8 mL) and extracted with CH2CI2 (2 x 50 mL). The combined organic layers were washed with brine (8 mL), dried (NA2SO4) and concentrated under reduced pressure. Purification by flash chromatography (35 g ISCO SILICA GEL column, EtOAc/hexane gradient) afforded a mixture of amides (114 mg) as a white solid. Separation of the isomers by CHIRAL COLUMN chromatography (Chiralpak AD column, 15% IPA/HEXANE isocratic) generated the corresponding separated amides A (41.6 mg, 40.6%) and B (31.2 mg, 27.4%). Data for isomer A : Chiral HPLC (Zorbax SB C18 4.6x75 mm, linear gradient over 8 min) retention time 7.23 min (purity 92%, 100% ee); Chiral analytical HPLC (Daicel CHIRALCEL AD 4.6x250 mm, 15% IPA/hexane) retention time 10.98 min (100% ee); LC/MS m/z 218 [M+H] + ; 1H NMR (CDCI3, 400) 5.35 (d, 1 H, J = 9.9 Hz) 4.48 (d, 1H, J = 9.9 Hz), 3.99 (ddd, 1 H, J = 13.2, 10.6, 3.3 Hz), 3.58- 3.65 (m, 1H), 3.03 (dt, 1H, J= 12.8, 8.8 Hz), 2.22 (bs, 1H), 2.07-2. 17 (m, 1H), 1.96 (ddd, 1H, J= 12.5, 8.8, 3.3 Hz) (m, 23H), 1.24-1. 28 (m, 1H), 0.86-0. 90 (m, 1 H), 0.57-0. 62 (td, 1 H, J = 5.5, 2.6 Hz). Data for isomer B : HPLC (Zorbax SB C18 4.6x75 mm, linear gradient over 8 min) retention time 7.22 min (96%); Chiral analytical HPLC (Daicel chiralcel AD 4.6x250 mm, 15% IPA/HEXANE) retention time 14.12 min (100% ee).
  • 22
  • [ 361442-00-4 ]
  • [ 841302-41-8 ]
  • [ 841302-42-9 ]
YieldReaction ConditionsOperation in experiment
97.5% With 4-methyl-morpholine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; In dichloromethane; at 20℃; for 20h; Method B from Example 3, Step 4a compound: A mixture of the acid of Example 1, Step 8 (96 mg, 0.30 MMOL), amine of Step 4a (35 mg, 0.29 MMOL, 0.97 equiv), PYBOP (236.1 mg, 0.45 mmol, 1.5 equiv) and N- methylmorpholine (0.09 mL, 0.84 mmol, 2.8 equiv) in CH2CI2 (2.5 mL) was stirred at rt for 20 h. The reaction was then quenched by the addition of 5% KHS04 (3 mL) and extracted with CH2CI2 (2 x 80 mL). The combined organic extracts were washed with brine (5 mL), dried (NA2S04), filtered and concentrated under reduced pressure to give a yellow oil. Purification by flash chromatography (35 g Isco silica gel column, EtOAc/hexane gradient followed by CH2CI2/MEOH gradient) afforded amide isomer A (110.5 mg, 97.5%) as a yellow oil : LC/MS M/Z 391 [M+H] + ; HPLC (Zorbax SB C18 4.6x75 mm, linear gradient over 8 min) retention time 7.23 min (99%); CHIRAL analytical HPLC (Daicel chiralcel AD 4.6x250 mm, 15% IPA/hexane) retention time 10.74 min (100% ee).
  • 24
  • [ 361442-00-4 ]
  • (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide hydrochloride [ No CAS ]
  • [ 361442-01-5 ]
YieldReaction ConditionsOperation in experiment
With 4-methyl-morpholine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; In acetic acid butyl ester; ethyl acetate; at 0℃; for 17.5h;Inert atmosphere; 7.2 Coupling of (S)-N-Boc-3-hydroxyadamant- l -yl glycine with (l S,3S,5S)-2- Azabicyclo[3.1 .0]hexane-3-dcarboxamide hydrochloride; 200mL ethyl acetate and 32mL N-methylmorpholine (286mmol, 5eq) were mixed in 500mL flask under nitrogen atmosphere and cooled to 0°C. Afterwards 19.0g (S)-N-Boc- 3-hydroxyadamant- l -yl glycine (58.4mmol, l eq) and 9.5g 1 S,3S,5S)-2-Azabicyclo [3. 1 .0]hexane-3-dcarboxamide hydrochloride (58.4mmol, l eq) were added and the mixture was stirred for 5min. 44.7g 50percent .(R).T3P in butyl acetate (70mmol, 1.2eq) were slowly added at 0°C and the mixture was stirred at 0°C for 3h 30min. After IPC using HPLC that showed not complete conversion 7.5g 50percent .(R).T3P in butyl acetate (l l Jmmol. 0.2eq) was added and the mixture was stirred for 14h and warmed to 20-25°C. Afterwards the fonned white solid was filtered off and the solid was washed two times each with 20mL ethyl acetate. The combined filtrate was hydrolyzed with 500mL 1 M NaOH. The phases were separated and the aqueous phase was extracted two times each with 150mL ethyl acetate. The combined organic phases were washed with 200mL saturated NaCl solution. The aqueous phase was extracted with 150mL ethyl acetate and the combined organic phases were dried over about 15g Sodium sulfate. After filtration the organic solvent was removed via distillation (rotovapor, 200-40mbar, 40°C) and the residue was dissolved in about 200mL methylene chloride. The solvent was again removed (rotovapor, 600-40mbar, 40°C) and during this left over butyl acetate was distilled of azeotropically. After drying (<30mbar, 40°C) 20.1g [( l S)-2-[(l S,3S,5S)-3-(aminocarbonyl)-2-azabicyclo[3. 1.0]hex-2- yl]- l -(3-hydroxy-tricyclo[3.3. 1.13,7]dec-l-yl)-2-oxoethyl]-carbamic acid- 1 , 1 -dimethyl- ethyl ester (48.4mmol, 79percent, purity: 83percent) as a amorphous solid was isolated.
69.15 g 2
A 2 L three-necked flask equipped with a thermometer, a mechanical stirrer and a gas inlet was charged with(alphaS)-alpha[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid (Formula 3) (50 grams,153.8 mmol). THF (200 ml) was added and stirred to produce a clear solution. The solution was cooled to -6°C in anacetone-dry ice-water bath. Methanesulfonyl chloride (Mes-Cl)(13.1 ml, 169 mmol, 1.1 equivalents) was then added asa single portion followed by diisopropylethylamine (94 ml, 539 mmol, 1.1 equivalents). The diisopropylethylamine wasadded slowly over a period of about 4 minutes to keep the internal temperature below 8°C. The reaction mixture wasstirred at 0°C until all acid was converted to mixed anhydride. (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamidehydrochloride salt (32.5 grams, 200 mmol, 1.1 equivalents) and hydroxybenzotriazole (HOBT) (1.04 grams, 7.6 mmol,0.05 equivalents) were then added in a single portion and the flask was removed from the cooling bath. The reactionmixture was stirred at room temperature for 2 hours and then left overnight at room temperature.
  • 25
  • N-Boc-3'-hydroxyadamantylglycine [ No CAS ]
  • [ 361442-00-4 ]
YieldReaction ConditionsOperation in experiment
56% With (1R,2S)-2-Amino-1,2-diphenylethanol; In ethyl acetate; at 20℃; for 2h;Reflux; Resolution of racemate; To a solution of N-Boc-3-hydroxyadamantylglycine 6(1.0 g, 0.0031 mol) in 10 mL of ethyl acetate was added(1R,2S)-(-)-2-amino-1,2-diphenylethanol (0.66 g, 0.0031mol) at room temperature and the mixture was stirred under reflux for 2.0 hours. It was then allowed to cool gradually toroom temperature, and then stirred overnight. The occurring precipitate was isolated by filtration leading to a white solidsalt. After recrystallizing with ethyl acetate one more time,the white solid salt was dissolved in a co-solvent of 10 mLwater and 10 mL ethyl acetate, and pH 2 was adjusted by adding concentrated HCl. The organic phase was separated and the aqueous phase was extracted with 10 mL ethyl acetatethree times. The organic phases were combined, dried over anhydrous sodium sulfate, and filtrated. After filtration,the organic solvent was removed via distillation under reducedpressure, and the residue was recrystallized to afford(S)-N-Boc-3-hydroxyadamantylglycine [Yield: 0.28 g, 56percent(according to the theoretical value of (S)-N-Boc-3-hydroxyadamantylglycine),as a white solid: mp 178-179 °C, []20D = +25°(C=1, MeOH), 99percent ee (HPLC conditions: Daicel ChiralpakAD-H 2504.6 mm, 5m; n-hexane/isopro-panol=85/15;flow rate: 1 mL/minute; T=25 °C; 210 nm)].
  • 26
  • (αS)-α-[(1,1-dimethylethoxy)carbonyl]amino-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid [ No CAS ]
  • [ 361442-00-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In water; ethyl acetate;pH 3; 7.1 Racemic resolution of N-Boc-3-hydroxyadamant-l -yl glycine; 16. lg (lNo.,2S)-2-amino-l ,2-diphenylethanol (75.5mmol, 0.7eq) were suspended in a 2L 3 neck round bottom flask equipped with a mechanic stirrer, a reflux condenser and a dropping funnel in 200mL ethyl acetate. 35g N-Boc-3-hydroxyadamant-l -yl glycine (107.6mmol, leq) dissolved in 600mL ethyl acetate were added slowly via the dropping funnel over a period of 5min. l OOmL ethyl acetate were added via the dropping funnel to wash left over of N-Boc-3-hydroxyadamant-l-yl glycine. The mixture was stirred and after 20min a clear solution was observed. After lh a white suspension occurs. The suspension was heated to 70°C and 400mL ethyl acetate were added slowly over a period of 2h at this temperature until the suspension was dissolved. The mixture was cooled slowly to 20-25°C over 14h under permanent stirring. The occurring precipitate was isolated by filtration leading to 53g of a white solid which was dried at 40°C/<40mbar. 24.7g of the N-Boc-3- hydroxyadamant- 1 -yl glycine amine salt was isolated with an enantiomeric excess of 86percent. The solid was suspended in a 2L 3 neck round bottom flask equipped with a reflux condenser and a mechanic stirrer in lOOOmL ethyl acetate. The suspension was heated to 70°C and 200mL ethyl acetate was added slowly over a period of 1.5h until a clear solution occurs. The mixture was slowly cooled to room temperature and stirred at that temperature for 2.5h while a white precipitate occurred. The precipitate was isolated via filtration (44g) and dried at 40°C/<40mbar leading to 20.8g of N-Boc-3-hydroxyadamant- l -yl glycine amine salt. The solid was dissolved in 200mL water and 1 OOmL ethyl acetate. By adding 2M HC1 pH 3 was adjusted. The organic phase was separated and the aqueous phase was extracted with 200mL ethyl acetate. The combined organic phase was dried over about l Og sodium sulfate. After filtration the organic solvent was removed via distillation and the residue was dried (40°C/<40mbar) leading to 13.9g N-Boc-3-hydroxyadamant-l -yl glycine (42.7mmol, 79percent, 96.3percent ee). From the combined mother liquors remaining N-Boc-3- hydroxyadamant-l-yl glycine can be isolated using the same procedure via acidification and extraction leading to N-Boc-3-hydroxyadamant-l-yl glycine mainly containing the R- isomer. The chiral amine was recovered by basification of the combined aqueous phases and extraction with ethyl acetate.The (7^N-Boc-3-hydroxyadamant-l-yl glycine which had not been reacted was again subsected to the process of the present invention.
  • 29
  • [ 361441-97-6 ]
  • [ 361442-00-4 ]
YieldReaction ConditionsOperation in experiment
51% With potassium permanganate; water; potassium hydroxide; at 60 - 90℃; for 1.5h; A solution of KMnO4 (337 mg, 2.13 mmol, 1.1 equiv) in 2percent aq KOH (6 mL) was heated to 60°C and Step 7 compound in general method G (600 mg; 1. 94 mmol, 1 equiv) was added in portions, and heating increased to 90°C. After 1.5 h, the reaction was cooled to 0°C, EtOAc (50 mL) was added, and the mixture was carefully acidified to pH 3 with 1N HCl. The layers were separated and the aqueous was extracted with EtOAc (50 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (3.8x15 cm) with 2percent (200 mL), 3percent (200 mL), 4percent (200 mL), and 5percent (500 mL) MeOH/CH2Cl2 + 0.5percent HOAc. After isolation of the product, the material was chased with hexanes to afford a white solid (324 mg, 51percent): MS m/e 326 (m+H)+
18.6 g With potassium permanganate; tetrabutylammomium bromide; potassium hydroxide; In water; at 20 - 25℃; In an oven dried 3 neck flask, 46.4 g (0.293M) of potassium permanganate was dissolved at room temperature in 500 mL of DM water. And 9.9 g (0.176M) of KOH was added at room temperature and under stirring 0.5g (0.003M) of TBAB was added at room temperature. The reaction mass was cooled to 20-25° C. Slowly 50g (0.162M) of compound-V was added lot wise at 20 - 25° C for 1 hour by maintaining the temperature at 20 - 25° C and RPM of 40 - 45. The reaction mixture wasmaintained at 20-25° C for 20-25 hours with intermittent stirring for about 30 seconds after every one hour and maintaining for 20-25 hours in these conditions for completion of reaction. Upon completion of the reaction, mass was filtered, the filtrate ML's was cooled to 10-15°C and sodium bi sulphate solution was added to reduce the oxidizing agent followed by pH adjustment to 2.5 with IN HC1. The reaction mass was extracted with 300mL of MDC. The MDC layer was then distilled out and the residue was dissolved in ethyl acetate and material was isolated from ethyl acetate layer on cooling. The compound thus obtained was purified with ethyl acetate. The 18.6 g of desired compound-VI was obtained as white solid having HPLC purity more than 99.5 percent , any known dihydroxy impurity not more than 0.15 percent, any unknown impurity not more than 0.1percent and Isomer impurity not more than 0.05percent
  • 30
  • [ 361442-00-4 ]
  • [ 1564266-94-9 ]
  • 31
  • [ 361442-00-4 ]
  • [ 1564267-06-6 ]
  • 32
  • [ 361442-00-4 ]
  • [ 1564267-10-2 ]
  • 33
  • [ 361442-00-4 ]
  • [ 1564265-94-6 ]
  • 34
  • [ 361442-00-4 ]
  • (2S,4S,5R)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile [ No CAS ]
  • 35
  • [ 361442-00-4 ]
  • [ 1564266-00-7 ]
  • 36
  • [ 361442-00-4 ]
  • [ 709031-45-8 ]
  • [ 361442-01-5 ]
YieldReaction ConditionsOperation in experiment
98.1% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In ethyl acetate; acetonitrile;Large scale; 2.5 kg of acetonitrile, 1.77 kg of ethyl acetate and 2.03 kg of N,N-diisopropylethylamine were successively added to the reaction vessel, and the mixture was stirred for use. Then, the raw material A2.33 kg, saxagliptin intermediate 1 1.67 kg, hydroxybenzotriazole 1.11 kg, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride 1.51 were sequentially added. Kg, 2.83 kg of acetonitrile, stirred for 2-3 hours.After most of the acetonitrile was distilled off under reduced pressure, 20.90 kg of ethyl acetate was added to the mixture and stirred. After adjusting the pH to neutral, 11.80 kg of sodium chloride solution was added, stirred at room temperature, and allowed to stand and then removed to the aqueous layer. The organic phase was stirred by adding 12.76 kg of a 20% potassium hydrogencarbonate solution, and after standing, the aqueous layer was removed. The organic phase was stirred by adding 12.76 kg of a 20% potassium hydrogencarbonate solution, and after standing, the aqueous layer was removed.The organic phase was decomposed to 4.0-5.9 L under reduced pressure, and 5.80 kg of ethyl acetate was added, and then decomposed to 4.0-5.9 L under reduced pressure; the desolvation was stopped, the negative pressure in the autoclave was kept, the vacuum was turned off, and the temperature of the kettle was adjusted to 20- At 50 C, ethyl acetate was added, and the sample was tested. The above operation was repeated to make the water content less than 0.1%. The drum was packed, and the kettle was washed with ethyl acetate and charged into the same barrel to obtain 24.68 kg of the saxagliptin intermediate 2 in ethyl acetate. HPLC detection: yield 98.1%, purity 95.1%.
46% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In ethyl acetate; acetonitrile; for 3h; General procedure: To the mixture of 8a-b (1.0equiv), 15a-d (1.0equiv), HOBt (1.0equiv) and EDC·HCl (1.0equiv) was slowly added a homogeneous solution of DIPEA (3.0equiv) in acetonitrile and ethyl acetate. The resulting solution was stirred for 3h. Followed by addition of ethyl acetate and water with stirring. The seperated organic layer was washed with 1N HCl, 1N NaOH and saturated brine, dried over Na2SO4, purified by flash chromatography.
  • 37
  • [ 361442-00-4 ]
  • [ 1312338-82-1 ]
  • [ 1564266-87-0 ]
YieldReaction ConditionsOperation in experiment
93% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In ethyl acetate; acetonitrile; for 3h; General procedure: To the mixture of 8a?b (1.0equiv), 15a?d (1.0equiv), HOBt (1.0equiv) and EDC·HCl (1.0equiv) was slowly added a homogeneous solution of DIPEA (3.0equiv) in acetonitrile and ethyl acetate. The resulting solution was stirred for 3h. Followed by addition of ethyl acetate and water with stirring. The seperated organic layer was washed with 1N HCl, 1N NaOH and saturated brine, dried over Na2SO4, purified by flash chromatography.
  • 38
  • [ 361442-00-4 ]
  • [ 1564266-70-1 ]
  • (S)-N-Boc-3-hydroxyadamantylglycine-L-trans-4,5-methanoprolinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In ethyl acetate; acetonitrile; for 3h; General procedure: To the mixture of 8a?b (1.0equiv), 15a?d (1.0equiv), HOBt (1.0equiv) and EDC·HCl (1.0equiv) was slowly added a homogeneous solution of DIPEA (3.0equiv) in acetonitrile and ethyl acetate. The resulting solution was stirred for 3h. Followed by addition of ethyl acetate and water with stirring. The seperated organic layer was washed with 1N HCl, 1N NaOH and saturated brine, dried over Na2SO4, purified by flash chromatography.
  • 39
  • [ 361442-00-4 ]
  • [ 1564266-74-5 ]
  • [ 1564267-02-2 ]
YieldReaction ConditionsOperation in experiment
71% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In ethyl acetate; acetonitrile; for 3h; General procedure: To the mixture of 8a?b (1.0equiv), 15a?d (1.0equiv), HOBt (1.0equiv) and EDC·HCl (1.0equiv) was slowly added a homogeneous solution of DIPEA (3.0equiv) in acetonitrile and ethyl acetate. The resulting solution was stirred for 3h. Followed by addition of ethyl acetate and water with stirring. The seperated organic layer was washed with 1N HCl, 1N NaOH and saturated brine, dried over Na2SO4, purified by flash chromatography.
  • 43
  • [ 361442-00-4 ]
  • (1S,3S,5S)-6-[14C]-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrochloride [ No CAS ]
  • C22(14)CH33N3O4 [ No CAS ]
  • 44
  • [ 361442-00-4 ]
  • [ 1572922-56-5 ]
  • [ 1572922-57-6 ]
  • 45
  • [ 59768-71-7 ]
  • [ 361442-00-4 ]
  • 46
  • [ 1660-04-4 ]
  • [ 361442-00-4 ]
  • 47
  • [ 16091-98-8 ]
  • [ 361442-00-4 ]
  • 48
  • [ 16091-97-7 ]
  • [ 361442-00-4 ]
  • 49
  • [ 2094-72-6 ]
  • [ 361442-00-4 ]
  • 50
  • [ 361442-00-4 ]
  • (1S,3S,5S)-2-[(2S)-2-triphenylmethylamino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide [ No CAS ]
  • 51
  • [ 361442-00-4 ]
  • (1S,3S,5S)-2-[(2S)-2-tritylamino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile [ No CAS ]
  • 52
  • [ 361442-00-4 ]
  • [ 709031-78-7 ]
  • 53
  • [ 361442-00-4 ]
  • [ 865999-64-0 ]
YieldReaction ConditionsOperation in experiment
90% With hydrogenchloride; In dichloromethane; isopropyl alcohol; at 10 - 35℃; for 8h; Example 1 Preparation of (lS)-a-amino-3-hydroxyadamantane-acetic acid hydrochloride A solution of (lS)-l-[[(l,l-Dimethylethoxy)carbonyl]amino]-3-hydroxyadamantane-l-acetic acid (1.0 g) in dichloromethane (10 ml) at 10-20°C was mixed with 20-25percent isopropanol-HCl (2 ml) and stirred at 25-35°C for 8 hours. Solvent was evaporated from the reaction mixture to give the product (lS)-a-amino-3-hydroxyadamantane-acetic acid hydrochloride as a solid (0.72 g). (Yield: 90.0percent)
  • 54
  • [ 361442-00-4 ]
  • (1S)-1-[triphenylmethylamino]-3-hydroxyadamantane-1-acetic acid [ No CAS ]
  • 55
  • [ 361442-00-4 ]
  • [ 709031-45-8 ]
  • [ 76-83-5 ]
  • (1S,3S,5S)-2-[(2S)-2-triphenylmethylamino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 6 Preparation of (lS,3S,5S)-2-[(2S)-2-tritylamino-2-(3-hydroxyadamantan-l-yl)acetyl]-2- azabicyclo[3.1.0]hexane-3-carboxamide Tert-butoxycarbonylamino-(3-hydroxy-adamantan-l-yl)-acetic acid (100 g; 0.307 mole) was added to dichloromethane (500 ml) with stirring. The methanesulfonic acid salt of (1S,3S,5S)- 2-azabicyclo[3.1.0]hexane-3-carboxamide (64.8 g; 0.292 mole) was added, and the reaction mixture was stirred for 15 minutes at 25-35°C. In a separate flask, 1-hydroxybenzotriazole monohydrate (11.8 g; 0.077 mole) and triethylamine (34.2 g) were added to dichloromethane (500 ml) and stirred to form a solution. This solution was added to the reaction mixture gradually over 30 minutes at 25-30°C. The reaction mixture was then cooled to 5-15°C, 1- ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HC1) (70.6 g) was added, and the mixture was stirred for 15 minutes at 5-15°C. Triethylamine (65.2 g) was added to the reaction mixture and stirred for 30 minutes. Temperature of the reaction mixture was raised to 25-35°C and stirred continuously for 12 hours. Reaction completion was confirmed by HPLC. Water (500 ml) was added, the mixture was stirred, and the organic layer was separated. The organic layer was washed with dilute hydrochloric acid solution (500 ml, prepared by adding concentrated hydrochloric acid (60 ml) to water (440 ml)), and further washed with sodium bicarbonate solution (3 times), followed by washing with sodium chloride solution. Hydrogen chloride in isopropanol (14.2percent w/w, 315.6 g) was added over 60 minutes, and the mixture was stirred for 4 hours. Completion of the reaction was confirmed by HPLC. The mixture was distilled under vacuum to remove dichloromethane. Toluene was added to the residue and distilled under vacuum. Acetonitrile (400 ml) was added to the residue followed by addition of triethylamine (79.2 g) over 15 minutes with stirring. The reaction mixture was cooled to 10- 20°C, and trityl chloride (72.7 g) was added gradually, followed by stirring for 2 hours. Completion of the reaction was confirmed by HPLC. The mixture was distilled under vacuum to remove acetonitrile. Toluene was added to the residue and distilled under vacuum. Toluene (500 ml) followed by water (500 ml) were added to the residue, the mixture was heated at 45- 55°C and filtered and dried to obtain the product. (Yield=60.3percent; HPLC purity=94percent) Mass: 576 [M+H]+ 1H-NMR (CD3OD) delta: 7.43-7.45 (5 H, d), 7.06-7.17 (10 H, m), 4.50 (1 H, s), 3.84-3.87 (1 H, dd), 3.42 (1 H, s), 3.09-3.13 (1 H, m), 2.87-2.91 (1 H, m), 2.15-2.23 (1 H, m), 2.09 (1 H, s), 1.90-1.92 (1 H, d), 1.42-1.77 (13 H, m), 1.19-1.22 (1 H, t), 0.72-0.76 (1 H, m), 0.50-0.55 (1H, m)
  • 56
  • 3-hydroxytricyclo[3.3.1.13'7]decane-1-carbaldehyde [ No CAS ]
  • [ 361442-00-4 ]
  • 57
  • C11H17O5S(1-)*Na(1+) [ No CAS ]
  • [ 361442-00-4 ]
  • 58
  • (2S)-[((1S)-2-hydroxy-1-phenylethyl)amino]-(3-hydroxytricyclo[3.3.1.13'7]dec-1-yl)ethanenitrile [ No CAS ]
  • [ 361442-00-4 ]
  • 59
  • (2S)-[3-chlorotricyclo[3.3.1.13'7]dec-1-yl]-[((1S)-2-hydroxy-1-phenylethyl)amino]ethanoic acid hydrochloride [ No CAS ]
  • [ 361442-00-4 ]
  • 60
  • [ 24424-99-5 ]
  • (2S)-amino[3-chlorotricyclo[3.3.1.13'7]dec-1-yl]ethanoic acid hydrochloride [ No CAS ]
  • [ 361442-00-4 ]
YieldReaction ConditionsOperation in experiment
1.16 g A mixture of potassium carbonate (2.5 g), water (17 mL), and tetrahydrofuran (8.5 mL) was stirred for 5 minutes at 26°C, then cooled to 3°C over 15 minutes. (2
  • 61
  • [ 42711-75-1 ]
  • [ 361442-00-4 ]
  • 62
  • [ 38584-37-1 ]
  • [ 361442-00-4 ]
  • 63
  • [ 361442-00-4 ]
  • C29H49N3O5Si [ No CAS ]
  • 64
  • [ 361442-00-4 ]
  • C29H47N3O4Si [ No CAS ]
  • 65
  • [ 143467-20-3 ]
  • [ 361442-00-4 ]
  • 66
  • C12H18NO3(1-)*Na(1+) [ No CAS ]
  • [ 361442-00-4 ]
  • 67
  • C17H27NO5*C20H24N2O2 [ No CAS ]
  • [ 361442-00-4 ]
YieldReaction ConditionsOperation in experiment
0.96 g With hydrogenchloride; In water; ethyl acetate;pH 2; To a solution of compound 6 (2.5 g, 0.08 mol), quinidine (2.5 g, 0.06 mol) and absolute ethyl alcohol (20 mL) was stirred and refluxed for 5 min, then the mixture was cooled and filtered to give white solid, which was dissolved in ethyl acetate (20 mL). Afterwards, 20 mL water was added, and the solution was adjusted to pH = 2 with hydrochloric acid and the organic phase was isolated. Then the water phase was extracted with ethyl acetate (10 mL x 3) and the combined organic solvent was distilled off under depressurization. Eventually, the residue was recrystallized from ethyl acetate/petroleum ether and dried to give compound I (0.96 g, 77 percent yield). M.p. 179?180 °C; 99 percent ee (HPLC conditions: Daicel Chiralpak AD-H 250 x 4.6 mm, 5 mum; n-hexane/isopropanol= 85/15; flow rate: 1 mL/min; T = 25 °C; 210 nm); alpha20D = +25° (C = 1, CH3OH).
  • 68
  • C17H27NO5*C20H24N2O2 [ No CAS ]
  • [ 361442-00-4 ]
  • 69
  • [ 39917-38-9 ]
  • [ 361442-00-4 ]
  • 71
  • 2-(3-hydroxy-1-adamantyl)-2-hydroxyiminoacetic acid [ No CAS ]
  • [ 361442-00-4 ]
  • 72
  • 1S-(3-hydroxy-1-adamantyl)-(1R-phenyl-ethylamino)acetate hydrochloride [ No CAS ]
  • [ 361442-00-4 ]
  • 73
  • (S)-2-(3-hydroxy-1adamantyl)glycine ethyl ester [ No CAS ]
  • [ 361442-00-4 ]
  • 74
  • N-tert-butoxycarbonyl-2-(3-hydroxy-1-adamantyl)-D-glycine ethyl ester [ No CAS ]
  • [ 361442-00-4 ]
YieldReaction ConditionsOperation in experiment
98.1% With water; sodium hydroxide; In ethanol; at 18 - 65℃; for 2h; The compound N- tert-butoxycarbonyl-3-hydroxy-13 prepared in Example 1-adamantyl -D- reaction flask was added 10g of glycine ethyl ester, was dissolved in ethanol 100ml was added to clarify the 1.7g of sodium hydroxide ( 1.5 eq.) was dissolved in 20ml water, maintaining 18-22 deg.] C, was added dropwise to the reaction flask, maintaining the addition was complete the reaction 65 2 hours, the solvent was evaporated to dryness under reduced pressure, ethyl acetate was added 120ml, 60ml water extraction, with 6N aqueous hydrochloric acid, adjusting the pH = 4-5, standing layer, 100ml of the aqueous phase was extracted with ethyl acetate, the organic layers combined, evaporated to dryness under reduced pressure, a white solid, to give N- tert-butoxycarbonyl-3-hydroxy 1-adamantyl -D- glycine 9.02g, yield 98.10percent, chiral purity was 99percent.
  • 75
  • 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid ethyl ester [ No CAS ]
  • [ 361442-00-4 ]
  • 76
  • C22H29NO3 [ No CAS ]
  • [ 361442-00-4 ]
  • 77
  • [ 768-90-1 ]
  • [ 361442-00-4 ]
  • 78
  • α-oxotricyclo[3.3.1.13,7]decane-1-acetic acid methyl ester [ No CAS ]
  • [ 361442-00-4 ]
  • 79
  • [ 709031-34-5 ]
  • [ 361442-00-4 ]
  • 80
  • 3-hydroxy-α-oxotricyclo[3.3.1.13,7]decane-1-acetic acid methyl ester [ No CAS ]
  • [ 361442-00-4 ]
  • 81
  • [ 361442-00-4 ]
  • (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)-1-oxoethyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile benzoate [ No CAS ]
  • 82
  • [ 128665-98-5 ]
  • [ 361442-00-4 ]
  • 83
  • [ 709031-35-6 ]
  • [ 361442-00-4 ]
  • 84
  • [ 30074-09-0 ]
  • [ 361442-00-4 ]
  • 85
  • [ 361442-00-4 ]
  • (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide [ No CAS ]
  • [ 361442-01-5 ]
YieldReaction ConditionsOperation in experiment
89.3% 32.5 g of 100 mmol of 3-hydroxyadamantane-Boc-S-glycine (available from Shanghai Tongchang Biomedical Technology Co., Ltd.) was mixed with 13 g of 103 mmol of (1S, 3S, 5S) -2-azabicyclo [3.1.0] (Purchased from Shanghai Tongchang Biomedical Technology Co., Ltd.) were added to 350 mL of ethyl acetate, which had been precooled to 0 ° C, and 42.6 g of 330 mmol of diisopropylethylamine was slowly added dropwise to the mixed solution. The resulting mixed solution was stirred at 0 ° C for 30 minutes. 235 mL of 50 w / wpercent 140 mmol of ethyl acetate solution of propylphosphonic acid anhydride was slowly added to the above mixed solution, maintaining the reaction system temperature to not exceed 5 ° C during the addition. After the reaction system was stirred at 0 ° C for 30 minutes, the temperature was raised to room temperature and stirring was continued for 4 hours.200 mL of water was added to the reaction mixture and the mixture was stirred for another 20 minutes. The separated oil layer was further washed with 100 mL of deionized water, dried over 50 g of anhydrous sodium sulfate for 1 hour and filtered. The filtrate was concentrated by evaporation to 100 mL (38.6 g, yield 89.3percent, HPLC purity 96.1percent.
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