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[ CAS No. 2095719-92-7 ] {[proInfo.proName]}

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Chemical Structure| 2095719-92-7
Chemical Structure| 2095719-92-7
Structure of 2095719-92-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 2095719-92-7 ]

CAS No. :2095719-92-7 MDL No. :MFCD32874105
Formula : C29H31ClFN5O5 Boiling Point : -
Linear Structure Formula :- InChI Key :BVRGQPJKSKKGIH-PUAOIOHZSA-N
M.W : 584.04 Pubchem ID :129053037
Synonyms :

Calculated chemistry of [ 2095719-92-7 ]

Physicochemical Properties

Num. heavy atoms : 41
Num. arom. heavy atoms : 18
Fraction Csp3 : 0.38
Num. rotatable bonds : 10
Num. H-bond acceptors : 8.0
Num. H-bond donors : 3.0
Molar Refractivity : 154.17
TPSA : 125.91 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -7.8 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.18
Log Po/w (XLOGP3) : 2.91
Log Po/w (WLOGP) : 3.1
Log Po/w (MLOGP) : 1.71
Log Po/w (SILICOS-IT) : 4.36
Consensus Log Po/w : 3.05

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -4.96
Solubility : 0.00642 mg/ml ; 0.000011 mol/l
Class : Moderately soluble
Log S (Ali) : -5.22
Solubility : 0.00356 mg/ml ; 0.0000061 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -8.47
Solubility : 0.00000198 mg/ml ; 0.0000000034 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 4.71

Safety of [ 2095719-92-7 ]

Signal Word:Warning Class:
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:
Hazard Statements:H302-H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 2095719-92-7 ]

* 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 [ 2095719-92-7 ]

[ 2095719-92-7 ] Synthesis Path-Downstream   1~26

  • 1
  • [ 2095665-46-4 ]
  • [ 2095692-22-9 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
64.3% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃; 685 Example 685: (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1 -oxo-2,3-dihydro- 1 H-isoindol-2-yl)-N-[(1S)-1 -(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide Example 685: (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1 -oxo-2,3-dihydro- 1 H-isoindol-2-yl)-N-[(1S)-1 -(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide (3638) - (3639) (3640) A stirred solution of (R)-2-(6-(5-chloro-2-((oxan-4-yl)amino)pyrimidin-4-yl)-1-oxoisoindolin-2- yl)propanoic acid (70 mg, 0.168 mmol), (S)-2-amino-2-(3-fluoro-5-methoxyphenyl)ethanol, HCI (41 mg, 0.185 mmol) and triethylamine (0.094 ml, 0.672 mmol) in DMF (1 ml) was treated with TBTU (65 mg, 0.202 mmol) and stirred at room temperature overnight. The mixture was diluted with ethyl acetate (20 ml), was washed successively with 1 M KHS04 (10 ml), NaHC03 (10 ml), brine (2x 10 ml) and then water (4x 10 ml), was dried (MgS04) and evaporated. The residue was purified by chromatography (S1O2, 12 g column, 0- 5% EtOOH in EtOAc) to give a glass, which was triturated with ether (2 ml) to give a solid. The solid was collected by filtration, washed with ether (2x 1 ml) and dried under vacuum at 50°C overnight to give the title compound (64.3 mg, 64.3 %) as a cream solid. 1 H NMR (DMSO, 400 MHz) δ 8.56 (1 H, d), 8.44 (1 H, s), 8.07 - 8.00 (1 H, m), 7.97 (1 H, dd), 7.74 (1 H, d), 7.61 (1 H, s), 6.76 - 6.64 (3H, m), 4.99 (1 H, q), 4.91 (1 H, t), 4.86 - 4.70 (2H, m), 4.60 (1 H, d), 4.00 - 3.80 (3H, m), 3.76 (3H, s), 3.60 - 3.47 (2H, m), 3.40 - 3.33 (2H, m), 1.84 (2H, d), 1.59 - 1.39 (5H, m). ). LCMS: [M+H]+ = 584.
64.3% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;
Stage #1: (R)-2-(6-(5-chloro-2-((oxan-4-yl)amino)pyrimidin-4-yl)-1-oxoisoindolin-2-yl)propanoic acid; (S)-2-amino-2-(3-fluoro-5-methoxyphenyl)ethanol hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 10 - 15℃; Stage #2: With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 15 - 25℃; 1.5.3 Stage 3: Preparation of Compound I To a solution of(2) (1.0 wt, 1.0 mol eqTo a solution of(2) (1.0 wt, 1.0 mol eq) in DCM (12.5 vol) was added amine (3) (0.68 wt, 1.27 mol eq). The suspension was cooled to 10 to 15°C and DIPEA (1.67 vol, 4.0 mol eq) was charged. The resulting solution was stirred for 5 to 10 minutes prior to the portion wise additionof HATU (1.15 wt, 1.27 mol eq), maintaining the reaction temperature <25 °C. The mixture was stirred at 15 to 25°C until deemed complete by HPLC (<0.5% area (2), typically I h). Upon completion the reaction was concentrated under reduced pressure at up to 38 °C to give a thick, mobile orange oil. The residue was dissolved in EtOAc (10 vol) and washed with purified water (10 vol), 25%w/w ammonium chloride solution (2 x 10 vol), 8%w/w NaHCO3 solution (2 x 10 vol)and 13% w/w NaCI solution (6 x 10 vol), then dried over MgSO4 (1.0 wt). The solid was removed by filtration and the filter cake washed with ethyl acetate (2 x 2 vol). The filtrates were concentrated on a rotary evaporator at up to 40 °C to give crude Compound I as a pale yellow foam. Crude Compound I was purified by dry flash chromatography.Full conversion of (2) to Compound I was also observed when subjected to the aboveconditions but wherein 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) was used as the coupling agent instead of HATU, 4-dimethylaminopyridine (4-DMAP) was used as the base instead of DIPEA and dimethylformamide (DMF) was used as a solvent instead of DCM.) in DCM (12.5 vol) was added amine (3) (0.68 wt, 1.27 mol eq). The suspension was cooled to 10 to 15°C and DIPEA (1.67 vol, 4.0 mol eq) was charged. The resulting solution was stirred for 5 to 10 minutes prior to the portion wise additionof HATU (1.15 wt, 1.27 mol eq), maintaining the reaction temperature <25 °C. The mixture was stirred at 15 to 25°C until deemed complete by HPLC (<0.5% area (2), typically I h). Upon completion the reaction was concentrated under reduced pressure at up to 38 °C to give a thick, mobile orange oil. The residue was dissolved in EtOAc (10 vol) and washed with purified water (10 vol), 25%w/w ammonium chloride solution (2 x 10 vol), 8%w/w NaHCO3 solution (2 x 10 vol)and 13% w/w NaCI solution (6 x 10 vol), then dried over MgSO4 (1.0 wt). The solid was removed by filtration and the filter cake washed with ethyl acetate (2 x 2 vol). The filtrates were concentrated on a rotary evaporator at up to 40 °C to give crude Compound I as a pale yellow foam. Crude Compound I was purified by dry flash chromatography.
77 % With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at -3 - 3℃; Large scale; 5 Example 5: Preparation of (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propenamide, compound of Formula (I) A mixture of compound of Formula O (9.29 Kg, 98.2% assay, 1 eq), compound of Formula J-2 (6.06 Kg, 1.2 eq) and N-ethyldiisopropyl amine (12 Kg, 4 eq) in dichloromethane (247 Kg) was cooled to -3 to 3oC and TBTU (8.79 Kg, 1.2 eq) was added in five portions with 15 min interval between each portion. The reaction mixture was stirred at this temperature for 1 h and HPLC analysis indicated consumption of compound of Formula O, less than 1%. The reaction mixture was warmed to room temperature and washed two times with 10% aqueous hydrochloric acid (95 Kg) followed by two times with 10% aqueous K2HPO4(95 Kg). The organic layer washed with water (95 Kg) and distilled down to 5-6 volumes. Dichloromethane was swapped with anhydrous ethanol (143 Kg) and distilled down to 6 volumes. The ethanolic solution was heated to about 50oC and water (67 Kg) was added over 2 hours. The mixture was seeded with compound of Formula I (80 g) and stirred at this temperature for 10 hours. The resulting suspension was cooled to room temperature over 5 hours and stirred at this temperature for 3 hours, filtered and washed with a mixture of ethanol (15 Kg) and water (19 Kg). The wet cake was dried at 30 to 35oC with a stream of nitrogen gas until residual water was less than 4% to obtain crude compound of the Formula I (11.2 Kg). The crude product was dissolved in anhydrous ethanol (37 Kg) at about 50oC and water (22 Kg) was added over 1 h. Seeds of compound of Formula ( 40 g) were added and water (22 Kg) was added over 1 h. The mixture was stirred at about 50oC for about 2 hours and cooled to about 40oC over 1 h. The mixture was stirred at this temperature for 15 hours and cooled to room temperature over 5 hours. After stirring for 2 hours at room temperature, the resulting suspension was filtered and washed with a mixture of ethanol (16 Kg) and water (20 Kg). The wet cake was dried at about 35oC with a stream of nitrogen over 3 days until the water content was below 3%, to obtain compound of the Formula I as a white solid (10.3 Kg, 77 % yield; HPLC purity = 99.5 % area, chiral purity = 100% area) The product was analyzed by LCMS (Cortecs C18+, 90Å, 2.7 µm, 2.1 mm x 30 mm, 3 min method, 0.1% Formic acid, 5-100% MeCN/water): m/z 186.2 (M+H)+(ES+), at 0.10 min, 99% purity at 260 nm +/- 80nm. The amount of compound of Formula (Z-1) in the product is about 0.03% area by HPLC, and the amount of compound of Formula (Z-2) in the product is 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 3H), 7.03 (t, J = 1.9 Hz, 1H), 7.02 - 6.96 (m, 1H), 6.83 (dt, J = 11.0, 2.3 Hz, 1H), 5.54 (t, J = 5.1 Hz, 1H), 4.25 (t, J = 5.9 Hz, 1H), 3.78 (s, 3H), 3.72 (t, J = 5.2 Hz, 2H). 13C NMR (101 MHz, DMSO-d6) δ 162.79 (C, J = 242.6 Hz), 160.71 (C, J = 11.7 Hz), 139.05 (C, J = 9.9 Hz), 110.16 (CH, J = 2.6 Hz), 106.65 (CH, J = 22.9 Hz), 101.30 (CH, J = 25.0 Hz), 62.70 (CH2), 55.83 (CH3), 55.59 (CH, J = 2.1 Hz). 19F NMR (376 MHz, DMSO) δ -111.31.
77 % With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at -3 - 3℃; Large scale; 5 Example 5: Preparation of (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propenamide, compound of Formula (I) A mixture of compound of Formula O (9.29 Kg, 98.2% assay, 1 eq), compound of Formula J-2 (6.06 Kg, 1.2 eq) and N-ethyldiisopropyl amine (12 Kg, 4 eq) in dichloromethane (247 Kg) was cooled to -3 to 3oC and TBTU (8.79 Kg, 1.2 eq) was added in five portions with 15 min interval between each portion. The reaction mixture was stirred at this temperature for 1 h and HPLC analysis indicated consumption of compound of Formula O, less than 1%. The reaction mixture was warmed to room temperature and washed two times with 10% aqueous hydrochloric acid (95 Kg) followed by two times with 10% aqueous K2HPO4(95 Kg). The organic layer washed with water (95 Kg) and distilled down to 5-6 volumes. Dichloromethane was swapped with anhydrous ethanol (143 Kg) and distilled down to 6 volumes. The ethanolic solution was heated to about 50oC and water (67 Kg) was added over 2 hours. The mixture was seeded with compound of Formula I (80 g) and stirred at this temperature for 10 hours. The resulting suspension was cooled to room temperature over 5 hours and stirred at this temperature for 3 hours, filtered and washed with a mixture of ethanol (15 Kg) and water (19 Kg). The wet cake was dried at 30 to 35oC with a stream of nitrogen gas until residual water was less than 4% to obtain crude compound of the Formula I (11.2 Kg). The crude product was dissolved in anhydrous ethanol (37 Kg) at about 50oC and water (22 Kg) was added over 1 h. Seeds of compound of Formula ( 40 g) were added and water (22 Kg) was added over 1 h. The mixture was stirred at about 50oC for about 2 hours and cooled to about 40oC over 1 h. The mixture was stirred at this temperature for 15 hours and cooled to room temperature over 5 hours. After stirring for 2 hours at room temperature, the resulting suspension was filtered and washed with a mixture of ethanol (16 Kg) and water (20 Kg). The wet cake was dried at about 35oC with a stream of nitrogen over 3 days until the water content was below 3%, to obtain compound of the Formula I as a white solid (10.3 Kg, 77 % yield; HPLC purity = 99.5 % area, chiral purity = 100% area) The product was analyzed by LCMS (Cortecs C18+, 90Å, 2.7 µm, 2.1 mm x 30 mm, 3 min method, 0.1% Formic acid, 5-100% MeCN/water): m/z 186.2 (M+H)+(ES+), at 0.10 min, 99% purity at 260 nm +/- 80nm. The amount of compound of Formula (Z-1) in the product is about 0.03% area by HPLC, and the amount of compound of Formula (Z-2) in the product is 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 3H), 7.03 (t, J = 1.9 Hz, 1H), 7.02 - 6.96 (m, 1H), 6.83 (dt, J = 11.0, 2.3 Hz, 1H), 5.54 (t, J = 5.1 Hz, 1H), 4.25 (t, J = 5.9 Hz, 1H), 3.78 (s, 3H), 3.72 (t, J = 5.2 Hz, 2H). 13C NMR (101 MHz, DMSO-d6) δ 162.79 (C, J = 242.6 Hz), 160.71 (C, J = 11.7 Hz), 139.05 (C, J = 9.9 Hz), 110.16 (CH, J = 2.6 Hz), 106.65 (CH, J = 22.9 Hz), 101.30 (CH, J = 25.0 Hz), 62.70 (CH2), 55.83 (CH3), 55.59 (CH, J = 2.1 Hz). 19F NMR (376 MHz, DMSO) δ -111.31.

  • 2
  • [ 79669-50-4 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / 1,2-dichloro-ethane / 1 h / 85 - 90 °C / Inert atmosphere; Large scale 2.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 80 °C / Inert atmosphere 3.1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 88 - 104 °C / Inert atmosphere 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / 62 - 72 °C / Inert atmosphere 5.1: hydrogenchloride / toluene / 25 - 40 °C 6.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 15 - 95 °C 7.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 10 - 15 °C 7.2: 15 - 25 °C
  • 3
  • [ 79670-17-0 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 80 °C / Inert atmosphere 2.1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 88 - 104 °C / Inert atmosphere 3.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / 62 - 72 °C / Inert atmosphere 4.1: hydrogenchloride / toluene / 25 - 40 °C 5.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 15 - 95 °C 6.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 10 - 15 °C 6.2: 15 - 25 °C
  • 4
  • [ 2095633-67-1 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 88 - 104 °C / Inert atmosphere 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / 62 - 72 °C / Inert atmosphere 3.1: hydrogenchloride / toluene / 25 - 40 °C 4.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 15 - 95 °C 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 10 - 15 °C 5.2: 15 - 25 °C
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / acetonitrile / 2 h / 80 - 85 °C / Large scale 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 3: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 18.25 h / 35 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / acetonitrile / 2 h / 80 - 85 °C / Large scale 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 3: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale

  • 5
  • [ 2095634-41-4 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / 62 - 72 °C / Inert atmosphere 2.1: hydrogenchloride / toluene / 25 - 40 °C 3.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 15 - 95 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 10 - 15 °C 4.2: 15 - 25 °C
Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 2: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 2: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 6
  • [ 2095634-69-6 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: hydrogenchloride / toluene / 25 - 40 °C 2.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 15 - 95 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 10 - 15 °C 3.2: 15 - 25 °C
  • 7
  • [ 2095665-45-3 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 8
  • [ 2095692-22-9 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
  • 9
  • [ 1016163-89-5 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / 1 h / 20 °C 1.2: 135 min / 20 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / acetonitrile / 2 h / 80 - 85 °C / Large scale 3.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 4.1: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / 1 h / 20 °C 1.2: 135 min / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 18.25 h / 35 °C 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / 1 h / 20 °C 1.2: 135 min / 20 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / acetonitrile / 2 h / 80 - 85 °C / Large scale 3.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 4.1: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 10
  • [ 29578-39-0 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 60 - 70 °C 1.2: 2 h / -30 - 30 °C 2.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP> / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 4.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 4.2: 10 °C / pH 1.4 / Large scale 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 60 - 70 °C 1.2: 2 h / -30 - 30 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 60 - 70 °C 1.2: 2 h / -30 - 30 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: TurboGrignard / tetrahydrofuran / 4 h / -15 - 25 °C 1.2: 14 h / -55 - 25 °C 2.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / pH 9.0 / Enzymatic reaction 3.2: 20 h / 20 - 25 °C 4.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 7 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 60 - 70 °C 1.2: 2 h / -30 - 30 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 7 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 60 - 70 °C 1.2: 2 h / -30 - 30 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 7 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 60 - 70 °C 1.2: 2 h / -30 - 30 °C 2.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP> / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 4.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 4.2: 10 °C / pH 1.4 / Large scale 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 7 steps 1.1: TurboGrignard / tetrahydrofuran / 4 h / -15 - 25 °C 1.2: 14 h / -55 - 25 °C 2.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / pH 9.0 / Enzymatic reaction 3.2: 20 h / 20 - 25 °C 4.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 5 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 65 °C 1.2: 2 h / -25 - 25 °C 2.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP>; ammonium formate / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 4.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 4.2: 10 °C / pH 1.4 / Large scale 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 65 °C 1.2: 2 h / -25 - 25 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 65 °C 1.2: 2 h / -25 - 25 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: TurboGrignard / tetrahydrofuran / 4 h / -15 - 25 °C 1.2: 14 h / -55 - 25 °C 2.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / 4 h / 20 - 35 °C / pH 9.0 / Enzymatic reaction 3.2: 20 h / 20 - 25 °C 4.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 7 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 65 °C 1.2: 2 h / -25 - 25 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 7 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 65 °C 1.2: 2 h / -25 - 25 °C 2.1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 3.1: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 4.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 7 steps 1.1: magnesium; diisobutylaluminium hydride / tetrahydrofuran / 65 °C 1.2: 2 h / -25 - 25 °C 2.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP>; ammonium formate / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 4.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 4.2: 10 °C / pH 1.4 / Large scale 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 7 steps 1.1: TurboGrignard / tetrahydrofuran / 4 h / -15 - 25 °C 1.2: 14 h / -55 - 25 °C 2.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 3.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / 4 h / 20 - 35 °C / pH 9.0 / Enzymatic reaction 3.2: 20 h / 20 - 25 °C 4.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 5.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C

  • 11
  • [ 1256466-71-3 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP> / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 3.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 3.2: 10 °C / pH 1.4 / Large scale 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 2: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 3: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 2: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 3: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 6 steps 1.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP> / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 3.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 3.2: 10 °C / pH 1.4 / Large scale 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 6 steps 1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 2: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 3: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 5: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 6: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 6 steps 1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 2: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 3: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 5: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 6: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 4 steps 1.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP>; ammonium formate / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 3.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 3.2: 10 °C / pH 1.4 / Large scale 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 2: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 3: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: titanium(IV) tetraethanolate / tetrahydrofuran / 60 °C / Large scale 2: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 3: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 6 steps 1.1: sodium hydroxide; water / tetrahydrofuran / 11 h / 20 - 30 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP>; ammonium formate / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 3.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 3.2: 10 °C / pH 1.4 / Large scale 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C

  • 12
  • [ CAS Unavailable ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 2: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 3 steps 1: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 2: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 2: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 5 steps 1: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 2: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 3 steps 1: borane-THF / tetrahydrofuran / 18 h / -40 - 20 °C 2: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 3 steps 1: borane-THF / tetrahydrofuran / 2 h / -40 - -30 °C 2: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale

  • 13
  • [ 2881059-77-2 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 2 steps 1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 5 - 20 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 14
  • [ 1212981-84-4 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrogenchloride / tert-butyl methyl ether; 1,4-dioxane / 3 h / 20 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 3 steps 1.1: acetonitrile / 30 min / Reflux 2.1: sodium hydrogencarbonate / water; dichloromethane 2.2: 30 min 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: hydrogenchloride / tert-butyl methyl ether; 1,4-dioxane / 3 h / 20 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 5 steps 1.1: acetonitrile / 30 min / Reflux 2.1: sodium hydrogencarbonate / water; dichloromethane 2.2: 30 min 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 2 steps 1: hydrogenchloride / tert-butyl methyl ether; 1,4-dioxane / 3 h / 20 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 3 steps 1.1: acetonitrile / 13.5 h / 20 °C / Reflux 2.1: sodium hydrogencarbonate / water; dichloromethane 2.2: 30 min 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: acetonitrile / 13.5 h / 20 °C / Reflux 2.1: sodium hydrogencarbonate / water; dichloromethane 2.2: 30 min 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C

  • 15
  • [ 2881059-72-7 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water; dichloromethane 1.2: 30 min 2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate / water; dichloromethane 1.2: 30 min 2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 3.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water; dichloromethane 1.2: 30 min 2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 16
  • [ 2095683-30-8 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
  • 17
  • [ 2095725-91-8 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
  • 18
  • [ 2095725-92-9 ]
  • [ 2244059-10-5 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
59 % With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In water; N,N-dimethyl-formamide at 80℃; 18 The crude boronate (3.4 g, presumed 6.64 mmol, 1.0 eq.) was dissolved in DMF (30 mL) and Pd(dppf)Cl2 (0.122 g, 0.166 mmol, 0.025 eq.) was added followed by the addition of compound of Formula D (1.65 g, 6.64 mmol, 1.0 eq.) and K3PO4 aqueous solution (3.52 g, 16.6 mmol, 2.5 eq in 30 mL water). The reaction mixture was then stirred at 80 °C for 12 hours (TLC showed consumption of compound of Compound D). The reaction was quenched by transferring reaction mixture to 20% NaCl solution (30 mL) and EtOAc (60 mL) was added, and phases were separated. The aqueous layer was extracted with EtOAc (30 mL). The combined organic layer was then successively washed with 5% citric acid solution (30 mL x 2), 5% K2HPO4 solution (30 mL x 2) and water (30 mL). The organic layer wasthen concentrated and purified by column chromatography to obtain partially pure fractions which were concentrated to obtain compound of Formula I as a brown foam (2.9 g, HPLC purity = 84.5%). The crude product was then recrystallized from EtOH/H2O (1:1) to obtain compound of the Formula (I) as a pale-yellow solid (2.3 g, yield = 59%, HPLC purity = 97% area).
59 % With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In water; N,N-dimethyl-formamide at 80℃; 18 The crude boronate (3.4 g, presumed 6.64 mmol, 1.0 eq.) was dissolved in DMF (30 mL) and Pd(dppf)Cl2 (0.122 g, 0.166 mmol, 0.025 eq.) was added followed by the addition of compound of Formula D (1.65 g, 6.64 mmol, 1.0 eq.) and K3PO4 aqueous solution (3.52 g, 16.6 mmol, 2.5 eq in 30 mL water). The reaction mixture was then stirred at 80 °C for 12 hours (TLC showed consumption of compound of Compound D). The reaction was quenched by transferring reaction mixture to 20% NaCl solution (30 mL) and EtOAc (60 mL) was added, and phases were separated. The aqueous layer was extracted with EtOAc (30 mL). The combined organic layer was then successively washed with 5% citric acid solution (30 mL x 2), 5% K2HPO4 solution (30 mL x 2) and water (30 mL). The organic layer wasthen concentrated and purified by column chromatography to obtain partially pure fractions which were concentrated to obtain compound of Formula I as a brown foam (2.9 g, HPLC purity = 84.5%). The crude product was then recrystallized from EtOH/H2O (1:1) to obtain compound of the Formula (I) as a pale-yellow solid (2.3 g, yield = 59%, HPLC purity = 97% area).
  • 19
  • [ 1822828-53-4 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP> / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 2.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 2.2: 10 °C / pH 1.4 / Large scale 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP> / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 2.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 2.2: 10 °C / pH 1.4 / Large scale 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 3 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP>; ammonium formate / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 2.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 2.2: 10 °C / pH 1.4 / Large scale 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; NAD<SUP>+</SUP>; ammonium formate / aq. buffer / 15.5 h / 28 - 32 °C / pH 9.1 / Large scale; Enzymatic reaction 2.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 2.2: 10 °C / pH 1.4 / Large scale 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C

  • 20
  • [ 1823324-98-6 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / pH 9.0 / Enzymatic reaction 2.2: 20 h / 20 - 25 °C 3.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 6 steps 1.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / pH 9.0 / Enzymatic reaction 2.2: 20 h / 20 - 25 °C 3.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 4 steps 1.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / 4 h / 20 - 35 °C / pH 9.0 / Enzymatic reaction 2.2: 20 h / 20 - 25 °C 3.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 6 steps 1.1: formic acid; sodium formate; water / ethanol / 8 h / 85 - 95 °C / Large scale 2.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / 4 h / 20 - 35 °C / pH 9.0 / Enzymatic reaction 2.2: 20 h / 20 - 25 °C 3.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 4.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C

  • 21
  • [ 38041-19-9 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / butan-1-ol; water / 6 d / 110 - 115 °C / Large scale 2: trichlorophosphate / acetonitrile / 6 h / 70 - 75 °C / Large scale 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 5 steps 1: N-ethyl-N,N-diisopropylamine / butan-1-ol; water / 6 d / 110 - 115 °C / Large scale 2: trichlorophosphate / acetonitrile / 6 h / 70 - 75 °C / Large scale 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 4: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 5: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1: N-ethyl-N,N-diisopropylamine / butan-1-ol; water / 6 d / 110 - 115 °C / Large scale 2: trichlorophosphate / acetonitrile / 6 h / 70 - 75 °C / Large scale 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 4: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 5: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 22
  • [ 2298204-43-8 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / pH 9.0 / Enzymatic reaction 1.2: 20 h / 20 - 25 °C 2.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / pH 9.0 / Enzymatic reaction 1.2: 20 h / 20 - 25 °C 2.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 3 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / 4 h / 20 - 35 °C / pH 9.0 / Enzymatic reaction 1.2: 20 h / 20 - 25 °C 2.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
Multi-step reaction with 5 steps 1.1: 2-amino-2-hydroxymethyl-1,3-propanediol; isopropylamine; pyridoxal 5'-phosphate / water; dimethyl sulfoxide / 4 h / 20 - 35 °C / pH 9.0 / Enzymatic reaction 1.2: 20 h / 20 - 25 °C 2.1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 3.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C

  • 23
  • [ 2881059-73-8 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 2 steps 1: hydrogenchloride / dichloromethane; 1,4-dioxane / 15 h / 20 - 25 °C 2: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 24
  • [ CAS Unavailable ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 1.2: 10 °C / pH 1.4 / Large scale 2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 1.2: 10 °C / pH 1.4 / Large scale 2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 250 min / 0 °C 3.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / N,N-dimethyl-formamide / 4.5 h / 110 °C / Inert atmosphere 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 18 h / -10 - 0 °C / Large scale 1.2: 10 °C / pH 1.4 / Large scale 2.1: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 25
  • [ 1933609-52-9 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: trichlorophosphate / acetonitrile / 6 h / 70 - 75 °C / Large scale 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; N,N-dimethyl-formamide / 12 h / 80 °C
Multi-step reaction with 4 steps 1: trichlorophosphate / acetonitrile / 6 h / 70 - 75 °C / Large scale 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 3: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 4 steps 1: trichlorophosphate / acetonitrile / 6 h / 70 - 75 °C / Large scale 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 3: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 4: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
  • 26
  • [ 2244059-10-5 ]
  • [ 2095719-92-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 2: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 75 min / -3 - 3 °C / Large scale
Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; acetonitrile / 48 h / 70 - 75 °C / Large scale 2: trifluoroacetic acid / dichloromethane / 35 h / 20 - 30 °C / Large scale 3: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / -3 - 3 °C / Large scale
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