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[ CAS No. 1057652-23-9 ] {[proInfo.proName]}

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Chemical Structure| 1057652-23-9
Chemical Structure| 1057652-23-9
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Product Details of [ 1057652-23-9 ]

CAS No. :1057652-23-9 MDL No. :MFCD27938576
Formula : C11H13NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :JBZSPPTWLZNDBH-UHFFFAOYSA-N
M.W :191.23 Pubchem ID :127255365
Synonyms :

Calculated chemistry of [ 1057652-23-9 ]

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.36
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 54.59
TPSA : 52.32 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.05 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.22
Log Po/w (XLOGP3) : 2.0
Log Po/w (WLOGP) : 1.88
Log Po/w (MLOGP) : 1.84
Log Po/w (SILICOS-IT) : 2.02
Consensus Log Po/w : 1.99

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.4
Solubility : 0.753 mg/ml ; 0.00394 mol/l
Class : Soluble
Log S (Ali) : -2.73
Solubility : 0.36 mg/ml ; 0.00188 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.72
Solubility : 0.367 mg/ml ; 0.00192 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.6

Safety of [ 1057652-23-9 ]

Signal Word:Warning Class:
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501 UN#:
Hazard Statements:H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1057652-23-9 ]

* 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 [ 1057652-23-9 ]

[ 1057652-23-9 ] Synthesis Path-Downstream   1~32

  • 1
  • [ 1057652-23-9 ]
  • [ 2191433-08-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: acetic acid / 0.5 h / 5 - 10 °C 1.2: 0 - 30 °C 2.1: copper(ll) bromide; tert.-butylnitrite / acetonitrile / 12 h / 30 °C
Multi-step reaction with 2 steps 1: acetic acid; bromine / 0 - 30 °C 2: copper(ll) bromide; tert.-butylnitrite / acetonitrile / 12 h / 30 °C
Multi-step reaction with 2 steps 1: bromine; acetic acid / water / 2 h / 0 - 20 °C 2: isopentyl nitrite; copper(I) bromide / acetonitrile / 1 h / 20 °C / Inert atmosphere; Cooling with ice
  • 2
  • [ 1057652-23-9 ]
  • [ CAS Unavailable ]
  • [ 2191433-07-3 ]
YieldReaction ConditionsOperation in experiment
55% With bromine; acetic acid In water at 0 - 20℃; for 2h; B.10.10.1 Methyl 2-amino-4-cyclopropylbenzo[d]thiazole-6-carboxylate To a mixture of sodium thiocyanate (1.3 g, 16 mmol) in HOAc (15 mL) at 0°C was added dropwise a solution of intermediate N1 (0.77 g, 4.0 mmol) in HOAc (15 mL) followed by the addition of Bromine (0.25 mL, 4.83 mmol) dropwise. The reaction mixture was stirred at rt for overnight. Water (50 mL) was added and stirred at rt for 2 h. The yellow precipitate was filtered. The solid obtained was diluted in DCM/MeOH (9/1) and basified with NH3aq until pH 8. The resulting mixture was filtered through a short pad of Celite. The organic layer was evaporated till dryness and the residue was taken up in MeOH and stirred overnight at rt. The solid was filtered and rinsed with MeOH and dried in vacuo to give intermediate N2 (0.55 g, 55%) as a yellow solid.
Stage #1: methyl 4-amino-3-cyclopropylbenzoate; sodium thiocyanide With acetic acid at 5 - 10℃; for 0.5h; Stage #2: With bromine at 0 - 30℃; 11.2 Step 2. Methyl2-amino-4-cyclopropyl-1,3-benzothiazole-6-carboxylate (A-7c) To a 500 mL round-bottom flask containing methyl4-amino-3-cydopropylbenzoateA-7b (16 g, 83.67 mmol, 1.0 equiv.) and AcOH (200 mL) was added sodium thiocyanate(27.13 g, 334.64 mmol, 4.0 equiv.) and the resulting mixture wa.s stirred for 0.5 hat 5-10 °C.A solution of bromine (13 3 g, 83.22 mmoL 0.99 equiv.) in AcOH (1 00 mL) was then added20 drop'.vise with at 0-5 °C and the resulting mixture '.vas stirred at 0-5°C for 10 min and then at30 °C overnight. 1500 mL ofi-hO was then added and the pH of the aqueous solution wasadjusted to 8-9 using potassium carbonate. The resulting solids were collected by filtrationand dried in an oven under reduced pressure to afford 24 g (crude) ofmethyl2-amino-4-cyclopropyl-1 ,3-benzothiazole-6-carboxylate A-7c as an orange colored solid. The crude25 product was carried onto the next step without further purification.
With bromine; acetic acid at 0 - 30℃; 7.2 Step 2, Methyl 2-amino-4-cyclopropyl-l,3-benzothiazole-6-carboxylate (A-7c) To a 500 mL round-bottom flask was added methyl 4-amino-3-cyclopropylbenzoate A- 7b (16 g, 83.67 mmol, 1.0 equiv.), AcOH (200 mL) and NaSCN (27.13 g, 334.64 mmol, 4.0 equiv.), and the resulting mixture was stirred for 0.5 h at 5-10 °C, A solution of bromine (13,3 g, 83.22 mmol, 0.99 equiv.) in AcOH (100 mL) was then added dropwise at 0-5 °C and the resulting mixture was stirred at 0-5 °C for 10 min, then at 30 °C overnight. H2O was added (1500 mL) and the pH of the solution was adjusted to 8-9 using potassium carbonate. The resulting solids were collected by filtration and dried in an oven under reduced pressure to afford methyl 2-amino-4-cyclopropyl-l,3-benzothiazole-6-carboxylate A-7c (24 g) as an orange solid. The product was carried on to the next step without further purification.
  • 3
  • [ 106896-49-5 ]
  • [ 411235-57-9 ]
  • [ 1057652-23-9 ]
YieldReaction ConditionsOperation in experiment
96% With potassium phosphate; palladium diacetate; tricyclohexylphosphine In toluene at 100℃; Inert atmosphere; 11.1 Step j Methyl4-amino-3-cyclopropylbenzoate (A-7b) To a 1000 mL round-bottom flask, purged and maintained under an inert atmosphereofnitrogen, was added methyl4-amino-3-bromobenzoate A-7a (25 g, 108.67 mmol, 1.0equiv.), K3P0c~ (65 g, 306.21 mmol, 2.82 equiv.), toluene (50 mL), water (100 mL), P(Cy)3(2 8 g, 0.05 equiv.), Pd(OAc)2 (2.2.5 g, 10.02 mmol, ).09 equiv.), and cyclopropyl boronicacid (26 g, 302.69 mmol, 2.79 equiv.) and the resulting mixture was heated at 100 °C10 overnight. The resulting solids were filtered off and the filtrate vvas diluted ·with 200 mL ofH20 and extracted with ethyl acetate (200 mL x 3). The combined organic layers wereconcentrated in vacuo and the resulting residue Vas purified by silica gel columnchromatography eluting with ethyl acetate/petroleum ether (1 :20 to 1.10 a.nd then to 1 :5) toprovide19.9 g (96%) of methyl 4-amino-3-cyclopropylbenzoate A-7b a.s a light brown solid.
96% With potassium phosphate; palladium diacetate; tricyclohexylphosphine In water; toluene at 100℃; Inert atmosphere; 7.1 Step 1. Methyl 4-amino-3-cyciopropylbenzoate (A-7b) To a 1 L round-bottom flask, purged and maintained under an inert atmosphere of nitrogen, was added methyl 4-amino-3-bromobenzoate A-7a (25 g, 108.67 mmol , 1.0 equiv.), K3PO4 (65 g, 306.21 mmol, 2.82 equiv.), toluene (50 mL), water (100 mL), P(Cy)s (2.8 g, 0.05 equiv.), Pd(OAc)2 (2.25 g, 10.02 mmol, 0.09 equiv.), and cyclopropyl boronic acid (26 g, 302.69 mmol, 2.79 equiv.). The resulting mixture was heated at 100 °C overnight. The resulting solids were removed by filtration. The filtrate was diluted with H2O (200 mL) and extracted with ethyl acetate (200 mL x 3). The combined organic layers were concentrated in vacuo and the resulting residue was purified via silica gel column chromatography eluting with EtOAc PE (1 :20 to 1 : 10 and to 1 :5) to provide methyl 4-amino-3-cyclopropylbenzoate A-7b (19.9 g, 96%) as a light brown solid.
96% With palladium diacetate; tricyclohexylphosphine In water; toluene at 100℃; for 4h; Inert atmosphere; 41 Palladium acetate (48.8mg, 0.217mmol), tris(cyclohexyl)phosphine (61.0mg, 0.217mmol) and potassium phosphate (1.38g, 6.52mmol) were added to toluene (10mL) with compound 41a (500mg, 2.17mmol) dissolved )/Water (2mL) mixed solution.The resulting reaction solution was stirred for 4 hours under nitrogen protection and 100°C.The reaction solution was cooled and filtered through Celite. The crude product obtained by concentrating the filtrate under reduced pressure was purified by column chromatography (petroleum ether/ethyl acetate = 2/1) to obtain compound 41b as a yellow solid(400mg, 96% yield).
93% With potassium phosphate; tricyclohexylphosphine In water; toluene at 120℃; for 0.75h; Microwave irradiation; B.10.10.1 Methyl 4-amino-3-cyclopropylbenzoate To a solution of 4-amino-3-bromobenzoic acid methyl ester (1.0 g, 4.4 mmol) in toluene (15 mL), were added cyclopropylboronic acid (0.56 g, 6.5 mmol), K3PO4 (2.8 g, 13 mol), tricyclohexylphoshine (0.12 g, 0.44 mmol) and H2O (2 mL). The reaction mixture was purged again for 2 min then was heated at 120°C using a single mode microwave (Anton Paar Monowave 300) with a power output ranging from 0 to 850 W for 45 min. The reaction mixture was filtered through a pad of Celite and washed with EtOAc and H2O. The filtrate obtained was extracted with EtOAc and the organic layer was washed with brine, dried over MgSO4, filtered and evaporated till dryness. The residue was purified by preparative LC (regular SiOH 30 µm, 40 g Interchim, mobile phase gradient: from heptane / EtOAc from 100:0 to 70:30). The pure fractions were combined and evaporated under vacuum to give intermediate N1 as a yellow oil (0.77 g, 93%).

  • 4
  • [ 1065010-87-8 ]
  • [ 106896-49-5 ]
  • methyl 4-amino-3-cyclopropylbenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With potassium phosphate; palladium diacetate; ruphos In water; toluene at 110℃; for 2.5h; Inert atmosphere; 4 Example 4: compound (115) in Table I According to procedure (J), a solution of methyl 4-amino-3-bromobenzoate (3.00 g, 12.8 mmoles, 1 eq.) and potassium cyclopropyltrifluoroborate (2.84 g, 19.2 mmoles, 1.5 eq.) in toluene (52.5 mL) and water (13.5 mL) was degassed with argon during 5 minutes then tripotassium phosphate (6.88 g, 31.9 mmoles, 2.5 eq.), RuPhos (239 mg, 511 pmoles, 0.04 eq.) and palladium(II) acetate (57.9 mg, 256 pmoles, 0.02 eq.) were added. The reaction mixture was heated at H0°C and stirred for 2h30 under inert atmosphere. Upon cooling down to room temperature, it was filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic layers were dried over MgS04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 4-amino-3-cyclopropylbenzoate (2.02 g, 81 %).H1 NMR (400 MHz, d6-DMSO) δ7.53 (dd, J = 8.4, 2.0 Hz, 1H), 7.42 (d, J = 1.9 Hz, 1H), 6.63 (d, J = 8.4 Hz, 1H), 5.87 (s, 2H), 3.73 (s, 3H), 1.65 (tt, J = 8.3, 5.4 Hz, 1H), 0.95 - 0.82 (m, 2H), 0.54 - 0.40 (m, 2H).
81% With potassium phosphate; palladium diacetate; ruphos In water; toluene at 110℃; for 2.5h; Inert atmosphere; 4 Example 4: compound (41) in Table I According to procedure (E), a solution of methyl 4-amino-3-bromobenzoate (3.00 g, 12.8 mmoles, 1 eq.) and potassium cyclopropyltrifluoroborate (2.84 g, 19.2 mmoles, 1.5 eq.) in toluene (52.5 mL) and water (13.5 mL) was degassed with argon during 5 minutes then tripotassium phosphate (6.88 g, 31.9 mmoles, 2.5 eq.), RuPhos (239 mg, 511 pmoles, 0.04 eq.) and palladium(II) acetate (57.9 mg, 256 pmoles, 0.02 eq.) were added. The reaction mixture was heated at 110°C and stirred for 2h30 under inert atmosphere. Upon cooling down to room temperature, it was filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic layers were dried over MgSO-u filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 4-amino-3-cyclopropylbenzoate (2.02 g, 81 %). NMR (400 MHz, ifc-DMSO) d 7.53 (dd, J = 8.4, 2.0 Hz, 1H), 7.42 (d, J = 1.9 Hz, 1H), 6.63 (d, J = 8.4 Hz, 1H), 5.87 (s, 2H), 3.73 (s, 3H), 1.65 (tt, J= 8.3, 5.4 Hz, 1H), 0.95 - 0.82 (m, 2H), 0.54 - 0.40 (m, 2H).
  • 5
  • [ 1057652-23-9 ]
  • [ 2408728-99-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2: water; sodium hydroxide / methanol / 3 h / 80 °C
Multi-step reaction with 2 steps 1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2: methanol; water; sodium hydroxide / 3 h / 80 °C
  • 6
  • [ 1057652-23-9 ]
  • [ 2408728-89-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2: water; sodium hydroxide / methanol / 3 h / 80 °C 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 20 °C
  • 7
  • [ 1057652-23-9 ]
  • [ 2408728-97-0 ]
  • [ 2408728-98-1 ]
YieldReaction ConditionsOperation in experiment
80% With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1.25h; Inert atmosphere; 4 According to procedure (A), a reaction mixture of l-bromo-3-(3- cyclohexylpropoxy)benzene (547 mg, 1.84 mmole, 1.1 eq.), methyl 4-amino-3-cyclopropyl- benzoate (320 mg, 1.67 mmol, 1 eq.), BrettPhos Pd G3 (31.9 mg, 33.5 pmol, 0.02 eq) and CS2CO3 (818 mg, 2.51 mmol, 1.5 eq.) in anhydrous DMF (8 mL) was degassed with argon and heated at 80°C for 75 minutes under inert atmosphere. The reaction mixture was then cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. Brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic layers were dried over MgS04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 4-[3-(3-cyclohexylpropoxy)phenyl]amino}-3-cyclopropylbenzoate (1.35 g, 80 %).H1 NMR (400 MHz, d6-DMSO) δ7.82 (s, 1H), 7.66 (dd, J = 8.5, 2.0 Hz, 1H), 7.54 (d, J = 2.0 Hz, 1H), 7.24 - 7.14 (m, 2H), 6.76 (d, J = 7.9 Hz, 1H), 6.73 (t, J = 2.1 Hz, 1H), 6.56 (dd, J = 8.1 , 2.2 Hz, 1H), 3.92 (t, J = 6.5 Hz, 2H), 3.78 (s, 3H), 1.94 (ddd, J = 13.8, 8.3, 5.4 Hz, 1H), 1.75 - 1.58 (m, 7H), 1.35 - 1.08 (m, 6H), 1.04 - 0.94 (m, 2H), 0.88 (q, J = 10.0, 9.3 Hz, 2H), 0.65 - 0.56 (m, 2H).
80% With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1.25h; Inert atmosphere; 4 According to procedure (Al), a reaction mixture of l-bromo-3-(3-cyclohexylpropoxy)benzene (547 mg, 1.84 mmole, 1.1 eq.), methyl 4-amino-3-cyclopropyl-benzoate (320 mg, 1.67 mmole, 1 eq.), BrettPhos Pd G3 (31.9 mg, 33.5 pmoles, 2 mol%) and CS2CO3 (818 mg, 2.51 mmoles, 1.5 eq.) in anhydrous DMF (8 mL) was degassed with N2 and heated at 80°C for 75 minutes under inert atmosphere. The reaction mixture was cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic phases were dried over MgSO-i, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 4- { [3 -(3 -cy cl ohexylpropoxy)phenyl] amino } -3 - cy cl opropy lb enzoate (1.35 g, 80%). NMR (400 MHz, e-DMSO) d 7.82 (s, 1H), 7.66 (dd, J = 8.5, 2.0 Hz, 1H), 7.54 (d, J = 2.0 Hz, 1H), 7.24 - 7.14 (m, 2H), 6.76 (d, J= 7.9 Hz, 1H), 6.73 (t, J= 2.1 Hz, 1H), 6.56 (dd, J= 8.1, 2.2 Hz, 1H), 3.92 (t, J= 6.5 Hz, 2H), 3.78 (s, 3H), 1.94 (ddd, J = 13.8, 8.3, 5.4 Hz, 1H), 1.75 - 1.58 (m, 7H), 1.35 - 1.08 (m, 6H), 1.04 - 0.94 (m, 2H), 0.88 (q, ,/ = 10.0, 9.3 Hz, 2H), 0.65 - 0.56 (m, 2H).
  • 8
  • [ 1057652-23-9 ]
  • [ 2561548-77-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: bromine; acetic acid / water / 2 h / 0 - 20 °C 2: isopentyl nitrite; copper(I) bromide / acetonitrile / 1 h / 20 °C / Inert atmosphere; Cooling with ice 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / tetrahydrofuran; water / Inert atmosphere; Microwave irradiation
  • 9
  • [ 1057652-23-9 ]
  • [ 2561548-78-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: bromine; acetic acid / water / 2 h / 0 - 20 °C 2: isopentyl nitrite; copper(I) bromide / acetonitrile / 1 h / 20 °C / Inert atmosphere; Cooling with ice 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / tetrahydrofuran; water / Inert atmosphere; Microwave irradiation 4: lithium hydroxide monohydrate / tetrahydrofuran; water / 5 h / Reflux
  • 10
  • [ 1057652-23-9 ]
  • [ 2561547-75-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: bromine; acetic acid / water / 2 h / 0 - 20 °C 2: isopentyl nitrite; copper(I) bromide / acetonitrile / 1 h / 20 °C / Inert atmosphere; Cooling with ice 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / tetrahydrofuran; water / Inert atmosphere; Microwave irradiation 4: lithium hydroxide monohydrate / tetrahydrofuran; water / 5 h / Reflux 5: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 2 h / 20 °C
  • 11
  • [ 1057652-23-9 ]
  • [ 2567983-84-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine; dmap / tetrahydrofuran / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 0.5 h / Cooling with ice 3: phosphorus tribromide / diethyl ether / 1 h / Cooling with ice
  • 12
  • [ 1057652-23-9 ]
  • [ 2567983-83-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine; dmap / tetrahydrofuran / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 0.5 h / Cooling with ice
  • 13
  • [ 24424-99-5 ]
  • [ 1057652-23-9 ]
  • [ 2567983-82-6 ]
YieldReaction ConditionsOperation in experiment
78% With dmap; triethylamine In tetrahydrofuran at 20℃; for 2h; 41 Di-tert-butyl dicarbonate (753 mg, 3.45 mmol), triethylamine (397 mg, 3.92 mmol) and 4-dimethylaminopyridine (192 mg, 1.57 mmol) were added to the dissolved compound 41b (300 mg, 1.57 mmol) Tetrahydrofuran solution (5 mL).The resulting reaction liquid was stirred at 20°C for 2 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography (petroleum ether/ethyl acetate = 10/1) to obtain a white solid compound 41c(480m, yield 78%).
  • 14
  • [ 1057652-23-9 ]
  • [ 2607889-07-4 ]
  • [ 2592377-23-4 ]
YieldReaction ConditionsOperation in experiment
63% With palladium diacetate; potassium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 130℃; for 1.25h; Inert atmosphere; 1 According to route (Al), a mixture of 3-chloro-2-cyclopropy 1-N-(3-methylbutyl)benzamide (99.4 mg, 374 pmoles, 1.1 eq.), methyl 4-amino-3-cyclopropylbenzoate (65 mg, 340 pmoles, 1 eq.), Pd(OAc)2 (2.3 mg, 10.2 pmoles, 3 mol%), rac-BINAP (4.2 mg, 6.8 pmoles, 2 mol%) and K2CO3 (141 mg, 1.02 mmole, 3 eq.) in anhydrous toluene (1 mL) was degassed with N2 and heated at 130°C for 75 minutes under inert atmosphere. The reaction mixture was cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic phases were dried over MgS04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 3-cyclopropyl-4-({2- cyclopropyl-3-[(3-methylbutyl)carbamoyl]phenyl}amino)benzoate (95 mg, 63%). NMR (400 MHz, e-DMSO) d 8.17 (t, J = 5.6 Hz, 1H), 7.67 (dd, J = 8.5, 2.0 Hz, 1H), 7.63 (d, ./ = 1.7 Hz, 1H), 7.49 (s, 1H), 7.35 - 7.22 (m, 2H), 6.98 (dd, J = 7.2, 1.4 Hz, 1H), 6.91 (d, ./= 8.5 Hz, 1H), 3.78 (s, 3H), 3.29 - 3.21 (m, 2H), 1.98 - 1.78 (m, 2H), 1.66 (dq, J = 13.3, 6.7 Hz, 1H), 1.43 (q, J = 7.0 Hz, 2H), 1.07 - 0.99 (m, 2H), 0.92 (d, J = 6.6 Hz, 6H), 0.83 - 0.75 (m, 2H), 0.70 - 0.61 (m, 2H), 0.42 (q, J= 5.7 Hz, 2H).
  • 15
  • [ 1057652-23-9 ]
  • [ 2579117-14-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / tetrahydrofuran / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C
  • 16
  • [ 1057652-23-9 ]
  • [ 2592377-25-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; potassium carbonate; palladium diacetate / toluene / 1.25 h / 130 °C / Inert atmosphere 2: methanol; water; sodium hydroxide / 3 h / 80 °C
  • 17
  • [ 1057652-23-9 ]
  • [ 2579116-24-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; potassium carbonate; palladium diacetate / toluene / 1.25 h / 130 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C
  • 18
  • [ 1057652-23-9 ]
  • [ 2592377-31-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2: methanol; water; sodium hydroxide / 3 h / 80 °C
  • 19
  • [ 1057652-23-9 ]
  • [ 2579116-42-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C
  • 20
  • [ 1057652-23-9 ]
  • [ 2592377-35-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2: methanol; water; sodium hydroxide / 3 h / 80 °C
  • 21
  • [ 1057652-23-9 ]
  • [ 2579116-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C
  • 22
  • [ 1057652-23-9 ]
  • [ 2592377-39-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C
  • 23
  • [ 1057652-23-9 ]
  • [ 2579116-58-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C 4.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 4 h / 20 - 90 °C
  • 24
  • [ 1057652-23-9 ]
  • [ 2579116-39-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C
  • 25
  • [ 1057652-23-9 ]
  • [ 2579116-63-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.33 h / 20 °C
  • 26
  • [ 1057652-23-9 ]
  • [ 2592377-50-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2: methanol; water; sodium hydroxide / 3 h / 80 °C
  • 27
  • [ 1057652-23-9 ]
  • [ 2592376-29-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2.1: methanol; water; sodium hydroxide / 3 h / 80 °C 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 16 h / 75 °C
  • 28
  • [ 1057652-23-9 ]
  • [ 2592377-62-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate / N,N-dimethyl-formamide / 1.25 h / 80 °C / Inert atmosphere 2: methanol; water; sodium hydroxide / tetrahydrofuran / 3 h / 80 °C
  • 29
  • [ 1057652-23-9 ]
  • [ 1566785-71-4 ]
  • [ 2592377-29-0 ]
YieldReaction ConditionsOperation in experiment
41% With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1.25h; Inert atmosphere; 2 According to route (A1), a reaction mixture of 3-bromo-2-chloro-N-cyclopropylb enzamide (108 mg, 0.392 mmole, 1.0 eq.), methyl 4-amino-3 -cyclopropyl- benzoate (75 mg, 0.392 mmole, 1.0 eq.), BrettPhos Pd G3 (26.7 mg, 29.4 pmoles, 7.5 mol%) and CS2CO3 (153 mg, 0.471 mmole, 1.2 eq.) in anhydrous DMF (2 mL) was degassed with N2 and heated at 80°C for 75 minutes under inert atmosphere. The reaction mixture was cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic phases were dried over MgSCE, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 4-[2-chloro-3- (cyclopropylcarbamoyl)phenyl]amino}-3-cyclopropylbenzoate (75 mg, 41%). NMR (500 MHz, ifc-DMSO) d 8.47 (d, ./ = 4.4 Hz, 1H), 7.69 (dd, J = 8.5, 2.0 Hz, 1H), 7.63 - 7.58 (m, 2H), 7.36 - 7.29 (m, 2H), 7.08 (s, 1H), 6.89 (d, J = 8.5 Hz, 1H), 3.79 (s, 3H), 2.82 (td, J = 7.3, 3.8 Hz, 1H), 1.88 (s, 1H), 1.01 - 0.96 (m, 2H), 0.69 (dd, J = 7.1, 2.2 Hz, 2H), 0.64 (dd, J= 5.4, 1.7 Hz, 2H), 0.53 (dd, ./= 3.9, 2.4 Hz, 2H).
  • 30
  • [ 39241-02-6 ]
  • methyl 4-amino-3-cyclopropylbenzoate [ No CAS ]
  • methyl 3-cyclopropyl-4-[3-(2-methylpropanamido)phenyl]amino}benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1.25h; Inert atmosphere; 3 According to route (Al), a reaction mixture of N-(3-bromophenyl)-2-methylpropanamide (279 mg, 1.15 mmole, 1.1 eq.), methyl 4-amino-3-cyclopropyl-benzoate (200 mg, 1.05 mmole, 1.0 eq.), BrettPhos Pd G3 (47.4 mg, 52.3 pmoles, 5 mol%) and CS2CO3 (409 mg, 1.26 mmole, 1.2 eq.) in anhydrous DMF (3 mL) was degassed with N2 and heated at 80°C for 75 minutes under inert atmosphere. The reaction mixture was cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic phases were dried over MgS04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 3 -cy clopropyl-4- { [3-(2- methylpropanamido)phenyl]amino}benzoate (368 mg, 99%). NMR (400 MHz, d6- DMSO) d 9.77 (s, 1H), 7.86 (s, 1H), 7.66 (dd, J= 8.5, 2.1 Hz, 1H), 7.59 (d, J= 1.9 Hz, 1H), 7.54 (d, J = 2.0 Hz, 1H), 7.25 - 7.17 (m, 2H), 7.14 (d, J = 8.5 Hz, 1H), 6.85 (d, J = 7.3 Hz, 1H), 3.78 (s, 3H), 2.63 - 2.53 (m, 1H), 1.95 (s, 1H), 1.09 (d, J = 6.8 Hz, 6H), 0.98 (dd, J= 8.3, 2.0 Hz, 2H), 0.60 (d, J= 3.6 Hz, 2H).
  • 31
  • [ 1057652-23-9 ]
  • [ 2592377-48-3 ]
  • [ 2592377-49-4 ]
YieldReaction ConditionsOperation in experiment
34% With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1.25h; Inert atmosphere; 7 According to route (Al), a reaction mixture of 2,3-dichloro-N-(1-methylcyclopropyl)pyridine-4-carboxamide (100 mg, 0.408 mmole, 1.0 eq.), methyl 4- amino-3-cyclopropyl-benzoate (78 mg, 0.408 mmole, 1.0 eq.), BrettPhos Pd G3 (18.5 mg, 20.4 pinoles, 5 mol%) and CS2CO3 (199 mg, 0.612 mmole, 1.5 eq.) in anhydrous DMF (2 mL) was degassed with N2 and heated at 80°C for 75 minutes under inert atmosphere. The reaction mixture was cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic phases were dried over MgS04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 4-({3-chloro-4-[(l- methylcyclopropyl)carbamoyl]pyridin-2-yl}amino)-3-cyclopropylbenzoate (56 mg, 34%).
  • 32
  • [ 1057652-23-9 ]
  • [ 1872698-65-1 ]
  • [ 2592377-61-0 ]
YieldReaction ConditionsOperation in experiment
25% With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1.25h; Inert atmosphere; 12 According to route (Al), a reaction mixture of 3-bromo-2-chloro-N-(1-methyl cyclopropyl)benzami de (226 mg, 0.784 mmole, 1.0 eq.), methyl 4-amino-3-cyclopropyl-benzoate (150 mg, 0.784 mmole, 1.0 eq.), BrettPhos Pd G3 (35.6 mg, 39.2 pmoles, 5 mol%) and CS2CO3 (383 mg, 1.18 mmole, 1.5 eq.) in anhydrous DMF (4 mL) was degassed with N2 and heated at 80°C for 75 minutes under inert atmosphere. The reaction mixture was cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic phases were dried over MgS04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give methyl 4-({2-chloro-3-[(l- methylcyclopropyl)carbamoyl]phenyl}amino)-3-cyclopropylbenzoate (77 mg, 25%). NMR (400 MHz, rfe-DMSO) d 8.61 (s, 1H), 7.70 (dd, J= 8.5, 2.1 Hz, 1H), 7.63 - 7.59 (m, 2H), 7.35 - 7.29 (m, 2H), 7.04 (dd, J = 6.3, 2.7 Hz, IH), 6.90 (d, ./= 8.5 Hz, 1H), 3.80 (s, 3H), 1.89 (ddd, J = 13.5, 8.3, 5.4 Hz, 1H), 1.40 (s, 3H), 1.02 - 0.95 (m, 2H), 0.78 - 0.70 (m, 2H), 0.67 - 0.62 (m, 2H), 0.62 - 0.57 (m, 2H).
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