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[ CAS No. 155135-61-8 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 155135-61-8
Chemical Structure| 155135-61-8
Chemical Structure| 155135-61-8
Structure of 155135-61-8 * Storage: {[proInfo.prStorage]}
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Product Details of [ 155135-61-8 ]

CAS No. :155135-61-8 MDL No. :MFCD07371619
Formula : C10H11NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :AOWXPFSYLFDFHC-UHFFFAOYSA-N
M.W : 177.20 Pubchem ID :16244442
Synonyms :

Calculated chemistry of [ 155135-61-8 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.3
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 52.81
TPSA : 38.33 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.11 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.95
Log Po/w (XLOGP3) : 1.79
Log Po/w (WLOGP) : 0.87
Log Po/w (MLOGP) : 1.55
Log Po/w (SILICOS-IT) : 2.0
Consensus Log Po/w : 1.63

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.28
Solubility : 0.939 mg/ml ; 0.0053 mol/l
Class : Soluble
Log S (Ali) : -2.21
Solubility : 1.08 mg/ml ; 0.00611 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.07
Solubility : 0.149 mg/ml ; 0.000843 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.78

Safety of [ 155135-61-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 155135-61-8 ]

* 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 [ 155135-61-8 ]

[ 155135-61-8 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 24424-99-5 ]
  • [ 155135-61-8 ]
  • [ 1313237-54-5 ]
YieldReaction ConditionsOperation in experiment
26% With dmap; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; A mixture of the product of Step 1 (3.63 g, 20.5 mmol), Boc20 (4.9 g, 22.6 mmol), DIREA (5.3 g, 41 mmol) and DMAP (0.25 g, 2.05 mmol) in THF (60 mL) was stirred at room temperature overnight. Water was then added and the mixture was extracted with ethyl acetate. The organic layers were combined, dried over sodium sulfate and evaporated. The residue was purified by silica gel column chromatography with EtOAc in hexanes (2 to 35%) to give the title compound (1.5 g, 26%). 1H NMR (CDC13) δ: 8.10 (br. s, 1H), 7.61 (dd, J=7.9, 1.3 Hz, 1H), 7.26 (t, J=8.0 Hz, 1H), 4.03 (t, J=8.7 Hz, 2H), 3.92 (s, 3H), 3.47 (t, J=8.7 Hz, 2H), 1.54-1.66 (br. s, 9H).
23% With dmap; In acetonitrile; at 20℃; for 16.0h; To a stirred solution of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> [155135-61-8] (1.2 g, 6.78 mmol) in acetonitrile (60 ml_), Boc¾0 (1.87 ml_, 8.14 mmol) and DMAP (166 mg, 1.36 mmol) were added and stirred at rt for 16 h. The reaction mixture was concentrated under reduced pressure. Water (30 mL) was added and extracted with ethyl acetate (2 x 30 ml_). The combined organic layers were washed with brine and dried over anhydrous Na2S04, filtered and evaporated under reduced pressure. The crude product was purified flash column chromatography (eluent: 2% ethyl acetate in hexane) to yield the title compound (430 mg, 23%). [LCMS RtE = 1.86 min, [M-Boc+H]+ = 178.1; TLC R, = 0.64 (ethyl acetate/hexane 20:80)].
  • 3
  • [ 155135-61-8 ]
  • [ 1313237-58-9 ]
  • 4
  • [ 155135-61-8 ]
  • [ 1427422-74-9 ]
  • [ 1427423-22-0 ]
YieldReaction ConditionsOperation in experiment
81% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; (a) To a suspension of K2CP3 (43 mg, 0.31 mmol) and <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (53 mg, 0.3 mmol) in dry DMF (1 mL) at 0 ºC was added dropwise a solution of 2-(bromomethyl)-4-chloro-1-((4-chloro-2-fluorobenzyl)oxy)benzene (114 mg, 0.31 mmol) in DMF (1mL). The reaction was stirred at RT overnight (TLC analysis showed complete conversion) and then the solution was poured onto crushed ice and extracted with EtOAc (x3). Combined organic extracts were washed with water, brine and dried over Na2SO4. Column chromatography on silica gel eluting with DCM gave methyl 1-(5-chloro-2-((4-chloro-2-fluorobenzyl)oxy)benzyl)indoline-4-carboxylate as a white solid (111 mg, 81% yield). 1H NMR (400 MHz, CDCl3) δ 7.36 (1H, dd), 7.30 (1H, d), 7.29 - 7.26 (2H, m), 7.21 (1H, dd), 7.14 - 7.09 (1H, m), 6.49 (1H, d), 5.09 (2H, s), 4.26 (2H, s), 3.88 (3H, s), 3.49 - 3.42 (2H, m), 3.41 - 3.34 (2H, m).
81% With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; a) To a suspension of K2CO3 (43 mg, 0.31 mmol) and methyl indoline-4- carboxylate (53 mg, 0.3 mmol) in dry DMF (1 mL) at 0 5C was added dropwise a solution of 2-(bromomethyl)-4-chloro-1 -((4-chloro-2-fluorobenzyl)oxy)benzene (1 14 mg, 0.31 mmol) in DMF (1 mL). The reaction was stirred at RT overnight (TLC analysis showed complete conversion) and then the solution was poured onto crushed ice and extracted with EtAcO (x3). Combined organic extracts were washed with water, brine and dried over Na2S04. Column chromatography on silica gel eluting with DCM gave methyl 1 -(5-chloro-2-((4-chloro-2- fluorobenzyl)oxy)benzyl)indoline-4-carboxylate as a white solid (1 1 1 mg, 81 % yield).1 H NMR (400 MHz, CDCI3) ? 7.36 (1 H, dd), 7.30 (1 H, d), 7.29 - 7.26 (2H, m), 7.21 (1 H, dd), 7.14 - 7.09 (1 H, m), 6.49 (1 H, d), 5.09 (2H, s), 4.26 (2H, s), 3.88 (3H, s), 3.49 - 3.42 (2H, m), 3.41 - 3.34 (2H, m).
  • 5
  • [ 155135-61-8 ]
  • [ 1427422-74-9 ]
  • [ 1427422-51-2 ]
  • 6
  • [ 155135-61-8 ]
  • [ 1285074-76-1 ]
  • [ 1428130-14-6 ]
YieldReaction ConditionsOperation in experiment
80% With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; a) To a suspension of K2CO3 (176 mg, 1 .27 mmol) and methyl indoline-4- carboxylate (215 mg, 1 .21 mmol) in dry DMF (3 mL) at 0 5C was added 2- (bromomethyl)-4-chloro-1 -((2,4-difluorobenzyl)oxy)benzene (443 mg, 1 .27 mmol) in DMF (3 mL). The reaction was stirred at RT overnight and then the solution was poured onto crushed ice and extracted with EtAcO (x2). Combined organic extracts were washed with water, brine and dried over Na2S04. Column chromatography on silica gel eluting with hexane:EtAcO gave the desired compound as a white solid. (430 mg, 80% yield).1 H NMR (400 MHz, Chloroform-d) ? 7.39 (td, J = 8.6, 6.3 Hz, 1 H), 7.28 (dd, J = 15.4, 1 .8 Hz, 1 H), 7.21 (dd, J = 8.6, 2.7 Hz, 1 H), 7.04 (t, J = 7.8 Hz, 1 H), 6.90 (d, J = 8.7 Hz, 1 H), 6.89 - 6.79 (m, 2H), 6.49 (dd, J = 7.8, 1 .0 Hz, 1 H), 5.08 (s, 2H), 4.25 (s, 2H), 3.88 (s, 3H), 3.50 - 3.41 (m, 2H), 3.41 - 3.32 (m, 2H).
  • 7
  • [ 155135-61-8 ]
  • [ 107-16-4 ]
  • methyl 1-(cyanomethyl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
5.6 g In water; at 110℃; for 15.0h; To a mixture of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (5.0 g, 28.22 mmol) in H20 (2.5 mL) was added 2-hydroxyacetonitrile (3.073 g, 29.63 mmol). The reaction was heated at 110 C for 15 h. The mixture was filtered. The solid was collected and recrystallized from MeOH (12 mL) to give the title compound (5.6 g). LCMS m/z = 217.2 [M+H]+; NMR (400 MHz, CDC13) δ 3.37-3.45 (m, 2H), 3.46-3.54 (m, 2H), 3.89 (s, 3H), 4.11 (s, 2H), 6.71 (d, 7 = 7.6 Hz, 1H), 7.22 (t, 7 = 7.9 Hz, 1H), 7.47 (dd, 7 1= 8.0 Hz, 72= 0.9 Hz, 1H).
  • 8
  • [ 155135-61-8 ]
  • [ 19481-82-4 ]
  • methyl 1-(1-cyanoethyl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With potassium carbonate; In acetonitrile; at 80℃; A mixture of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (114 mg, 0.643 mmol), potassium carbonate (270 mg, 1.954 mmol), and 2-bromopropanenitrile (277 μ, 3.267 mmol) in 2 ml CH3CN was stirred at 80C (oil bath) overnight. Mixture was purified by HPLC (CH3CN/H20 gradient + 0.1 % TFA). Fractions containing product were partly concentrated and residue was extracted with 1 M NaHC03and CH2C12. Organic phases were dried over MgS04, filtered, and concentrated to give methyl 1-(1- cyanoethyl)indoline-4-carboxylate (106 mg, 72 %). LCMS m/z = 331.4 [M+l]+. NMR (400 MHz, CDC13) δ 1.65 (d, 7 = 7.2 Hz, 3H), 3.19-3.31 (m, 2H), 3.52-3.67 (m, 2H), 3.88 (s, 3H), 4.57 (q, 7 = 7.2 Hz, 1H), 6.72 (d, 7 = 7.8 Hz, 1H), 7.19-7.23 (m, 1H), 7.36 (dd, J}= 7.8 Hz, 72= 0.8 Hz, 1H).
  • 9
  • [ 155135-61-8 ]
  • 1-(1-cyanoethyl)-N-methylindoline-4-carboxamide [ No CAS ]
  • 10
  • [ 155135-61-8 ]
  • tert-butyl (2-(4-(methylcarbamoyl)indolin-1-yl)propyl)carbamate [ No CAS ]
  • 11
  • [ 155135-61-8 ]
  • (x)C2HF3O2*C13H19N3O [ No CAS ]
  • 12
  • [ 155135-61-8 ]
  • N,4-dimethyl-1,2,3,4,6,7-hexahydro[1,4]diazepino[6,7,1-hi]indole-8-carboxamide dihydrochloride [ No CAS ]
  • 13
  • [ 155135-61-8 ]
  • methyl 1-(2-aminoethyl)indoline-4-carboxylate [ No CAS ]
  • 14
  • [ 155135-61-8 ]
  • methyl 1,2,3,4,6,7-hexahydro[1,4]diazepino[6,7,1-hi]indole-8-carboxylate [ No CAS ]
  • 15
  • [ 155135-61-8 ]
  • [ 2576-47-8 ]
  • methyl 1-(2-aminoethyl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.3 g at 122℃; for 15.0h; A mixture of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (2.1 g, 11.85 mmol) and 2-bromoethanamine hydrobromide (2.550 g, 12.44 mmol) was heated at 122 C for 15 h. The mixture was dissolved in 2 M HC1 and purified by HPLC to give the title compound (2.3 g). LCMS mlz = 221.2 [M+H]+; NMR (400 MHz, CD3OD) δ 3.21 (t, J = 6.6 Hz, 2H), 3.28-3.34 (m, 2H), 3.35-3.45 (m, 4H), 3.85 (s, 3H), 6.78 (d, J = 7.9 Hz, 1H), 7.14 (t, J = 7.9 Hz, 1H), 7.29 (dd, J}= 8.0 Hz, J2= 0.9 Hz, 1H).
  • 16
  • [ 155135-61-8 ]
  • tert-butyl 5-bromo-4-(hydroxymethyl)indoline-1-carboxylate [ No CAS ]
  • 17
  • [ 155135-61-8 ]
  • tert-butyl 5-bromo-4-(((tert-butyldimethylsilyl)oxy)methyl)indoline-1-carboxylate [ No CAS ]
  • 18
  • [ 155135-61-8 ]
  • tert-butyl 4-(((tert-butyldimethylsilyl)oxy)methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline-1-carboxylate [ No CAS ]
  • 19
  • [ 155135-61-8 ]
  • tert-butyl 5-(4,6-bis(benzyloxy)-5-((benzyloxy)carbonyl)-3-(((tert-butyldimethylsilyl)oxy)methyl)pyridin-2-yl)-4-(((tertbutyldimethylsilyl)oxy)methyl)indoline-1-carboxylate [ No CAS ]
  • 20
  • [ 155135-61-8 ]
  • tert-butyl 5-(4,6-bis(benzyloxy)-5-((benzyloxy)carbonyl)-3-(hydroxymethyl)pyridin2-yl)-4-(hydroxymethyl)indoline-1-carboxylate [ No CAS ]
  • 21
  • [ 155135-61-8 ]
  • 8-benzyl 1-(tert-butyl) 7,9-bis(benzyloxy)-2,3,4,6-tetrahydro-1H-pyrido[2',3':5,6]oxepino[3,4-e]indole-1,8-dicarboxylate [ No CAS ]
  • 22
  • [ 155135-61-8 ]
  • 8-benzyl 1-(tert-butyl) 7,9-bis(benzyloxy)-4,6-dihydro-1H-pyrido[2',3':5,6]oxepino[3,4-e]indole-1,8-dicarboxylate [ No CAS ]
  • 23
  • [ 39830-66-5 ]
  • [ 155135-61-8 ]
YieldReaction ConditionsOperation in experiment
73% With triethylsilane; trifluoroacetic acid; In dichloromethane; at 20℃; for 16h; To a solution of methyl lH-indole-4-carboxylate (5.0 g, 28.6 mmol) in dichloromethane (150 mL) and TFA (36 mL) was added triethylsilane (7.0 mL, 43.9 mmol). The mixture was stirred at room temperature for 16 hrs, then additional dichloromethane (350 mL) and water (200 mL) were added. The mixture was neutralized with concentrated ammonium hydroxide (approx.. 50 mL) and extracted with ethyl acetate (3X). The organic layers were combined, dried over sodium sulfate and evaporated. The residue was re-dissolved in a 1: 1 mixture of ether and hexane (100 mL), then 4N HC1 in dioxane (8 mL) was added. The resulting precipitate was collected by filtration. The obtained solid was treated with saturated sodium bicarbonate. The mixture was extracted with dichloromethane. The organic phase was combined, dried over sodium sulfate and evaporated to give the desired compound as a solid (3.63 g, 73%), which was used in the next step without purification. LC-MS 178.4 [M+H]+, RT 0.77 min. 1H NMR (CDC13) delta: 7.47 (dd, J=7.9, 0.6 Hz, 1H), 7.16 (t, J=7.9 Hz, 1H), 6.96 (d, J=7.6 Hz, 1H), 3.87-3.92 (s, 3H), 3.64-3.71 (m, 2H), 3.47 (t, J=8.4 Hz, 2H).
48% With sodium cyanoborohydride; acetic acid; at 15℃; for 5h; A solution of methyl lH-indole-4-carboxylate ( 2.60 g, 14.84 mmol ) in acetic acid ( 26 mL ) was cooled to 15 0 C and then treated with sodium cyanoborohydride ( 3.82 g, 0.061 mmol ) added in small portions over 30 min. After 5 h at 15 0 C, the reaction mixture was diluted with a mixture of ice and water ( 200 mL ) and carefully adjusted to pH 9 -10 with solid potassium carbonate. The aqueous phase was extracted three times with dichloromethane and the combined organic phase was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residual oil was chromatographed on silica gel ( elution dichloromethane - ethyl acetate 5 - 10 % ) to give 1.26 g ( 48 % yield ) of the title material as white solid. HPLC (Method A): 0.9 min ( tailing ). HRMS (ESI) calcd for C10Hi2NO2 [M+H]+ m/z 178.0863, found 178.0867. NMR (CDC13, 400 MHz) delta ppm: 7.32 (br. d, J = 7.9 Hz, 1H), 7.05 (br. t, J - 8 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 3.86 (s, 3H), 3.57 (t, J = 8.4 Hz, 2H), 3.37 (t, J = 8.4 Hz, 2H).
  • 24
  • [ 155135-61-8 ]
  • (2,3-dihydro-1H-indol-4-yl)methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With lithium aluminium tetrahydride; In tetrahydrofuran; at 23℃; for 3.0h;Inert atmosphere; A solution of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> ( 1.20 g, 6.77 mmol) in dry tetrahydrofuran ( 20 mL ) was treated at 23 0 C and under nitrogen with lithium aluminum hydride ( 0.35 g, 6.08 mmol) added in small portions over 20 min and the resulting mixture was stirred for 3 h. The reaction mixture was carefully quenched by successive addition of ethyl acetate ( 1 mL ), water ( 0.4 mL), 15 % aqueous sodium hydroxide ( 0.4 mL ) and water ( 1.2 mL ). The solid formed was filtered and the filtrate was concentrated under reduced pressure. Chromatography of the residual oil on silica gel ( elution ethyl acetate ) followed by distillation under vacuum ( bulb to bulb distillation, bp l05 - 110 C / 0.1 torr, air bath temperature ) gave 0.62 g ( 61 % yield ) of a white solid. HPLC (Method A): 0.13 min. HRMS (ESI) calcd for C9H12NO [M+H]+ m/z 150.0913, found 150.0932. NMR (CDC13, 400 MHz) δ ppm: 7.05 (t, J = 7.6 Hz, 1H), 6.74 (d, J = 7.1 Hz, 1H), 6.62 (d, J = 7.7 Hz, 1H), 4.64 (s, 2H), 3.60 (t, J = 8.4 Hz, 2H), 3.06 (t, J = 8.4 Hz, 2H).
  • 25
  • [ 155135-61-8 ]
  • tert-butyl 4-(((6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-yl)oxy)methyl)indoline-1-carboxylate [ No CAS ]
  • 26
  • [ 155135-61-8 ]
  • 6-(4-(indolin-4-ylmethoxy)-6-methoxybenzofuran-2-yl)-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole [ No CAS ]
  • 27
  • [ 155135-61-8 ]
  • (4-(((6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-yl)oxy)methyl)indolin-1-yl)(phenyl)methanone [ No CAS ]
  • 28
  • [ 815584-38-4 ]
  • [ 155135-61-8 ]
  • methyl 1-(4-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79.1% With dichloro[1,1′-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P′]palladium; palladium diacetate; caesium carbonate; In 1,4-dioxane; at 120℃; for 18.0h; A mixture of 2-bromo-4-((tert-butyldimethylsilyloxy)methyl)pyridine (2.02 g, 6.682 mmol), <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (1.18 g, 6.659 mmol), 1,1’-bis(di-tert- butylphosphino)ferrocene (327 mg, 0.692 mmol), diacetoxypalladium (80 mg, 0.356 mmol), and cesium carbonate (5.4 g, 16.57 mmol) in 40 mL dioxane was stirred at 120C (oil bath) for 18 h. The reaction mixture was filtered, concentrated and the resulting residue was purified by Biotage chromatography (Si02, hexane/AcOEt) to give methyl 1 -(4-((tert- butyldimethylsilyloxy)methyl)pyridin-2-yl)indoline-4-carboxylate (2.1 g, 79.1 %) as a colorless oil. LCMS m/z = 399.0 [M+1]. ‘H NMR (400 MHz, CDC13): ö ppm 0.13 (s, 6H), 0.97 (s, 9H), 3.59 (t, J= 8.6 Hz, 2H), 3.90 (s, 3H), 4.07 (t, J= 8.3 Hz, 2H), 4.74 (s, 2H), 6.72 (d, J= 5.0 Hz, 1H), 6.80 (s, 1H), 7.22-7.26 (m, 1H), 7.50 (d, J= 7.9 Hz, 1H), 8.27 (d, J= 5.0 Hz, 1H), 8.51 (d, J = 7.9 Hz, 1H).
  • 29
  • [ 155135-61-8 ]
  • 2-chloro-4-(3-(trifluoromethyl)benzyl)pyridine [ No CAS ]
  • methyl 1-(4-(3-(trifluoromethyl)benzyl)pyridin-2-yl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
24.1% With dichloro[1,1′-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P′]palladium; palladium diacetate; caesium carbonate; In 1,4-dioxane; at 135℃;Microwave irradiation; To a mixture of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (0.626 g, 3.534 mmol), 2-chloro-4-(3- (trifluoromethyl)benzyl)pyridine (1.00 g, 3.534 mmol) and 1,1 ‘-bis(di-tertbutylphosphino)ferrocene (0.185 g, 0.3 89 mmol) in dioxane (10 mL) were added palladium (II) acetate (39.67 mg, 0.177 mmol), and cesium carbonate (1.727 g, 5.301 mmol). The reaction was heated under microwave irradiation at 135C for 2 h. Additional palladium (II) acetate (20 mg, 0.O89mmol) and 1,1’-bis(di-tert-butylphosphino)-ferrocene (92 mg, 0.193 mmol) were added into the reaction mixture and heated at 135C for another 3 hours followed by heating at 135C overnight with conventional heating. The mixture was concentrated. The residue was dissolved in DCM and extracted with water. The organic phase was concentrated. The residue was purified by column chromatography (20-80% EtOAc/Hex, and then 20%-40% EtOAc/Hex) to give the title compound (351 mg, 0.85 1 mmol, 24.1 %) as a yellow solid. LCMS m/z = 413.3 [M+1] ‘H NMR (400 MHz, CDC13): ö ppm 3.57 (t, J = 8.73 Hz, 2H), 3.90 (s, 3H), 3.88-4.04 (m, 4H), 6.53 (s, 1H), 6.62 (dd, J= 1.14, 5.10 Hz, 1H), 7.23 (t, J= 8.01 Hz, 1H), 7.33-7.53 (m, SH), 8.26 (d, J= 5.04 Hz, 1H), 8.48 (d, J= 7.89 Hz, 1H).
  • 30
  • [ 155135-61-8 ]
  • 4-chloro-2-(3-(trifluoromethyl)benzyl)pyridine [ No CAS ]
  • methyl 1-(2-(3-(trifluoromethyl)benzyl)pyridin-4-yl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
62.7% With dichloro[1,1′-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P′]palladium; palladium diacetate; caesium carbonate; In 1,4-dioxane; at 130℃; for 3.0h; Methyl indoline-4-carboxylate (0.273 g, 1.542 mmol), 1,1’-bis(di-tert- butylphosphino)ferrocene (0.147 g, 0.308 mmol), palladium (II) acetate (34.63 mg, 0.154 mmol), cesium carbonate (0.754 g, 2.3 14 mmol) and 4-chloro-2-(3-(trifluoromethyl)benzyl)pyridine (0.419 g, 1.542 mmol) were taken up in dioxane (10.000 mL). The reaction was heated at 130C for 3 hours (in a heavy-walled sealed flask). The mixture was cooled to room temperature, filtered, and concentrated to dryness. The crude residue was purified by column chromatography (0-50-80 % EtOAc/Hex) to yield the title compound (0.4984 g, 1.209 mmol, 62.7 %) as a yellow solid. LCMS m/z = 413.2 [M+1]. ‘H NMR (400 MHz, CDC13): ö ppm 3.51 (t, J= 8.45 Hz, 2H), 3.90 (s, 3H), 3.99 (t, J= 8.46 Hz, 2H), 4.18 (s, 2H), 6.94-6.96 (m, 1H), 6.92 (dd, J= 5.86, 2.38 Hz, 1H),7.18 (t, J= 7.95 Hz, 1H), 7.32-7.36 (m, 1H), 7.40-7.46 (m, 1H), 7.47-7.53 (m, 3H), 7.57 (s, 1H),8.38 (a, J= 5.84 Hz, 1H).
  • 31
  • [ 155135-61-8 ]
  • 2-chloro-6-(3-(trifluoromethyl)benzyl)pyridine [ No CAS ]
  • methyl 1-(6-(3-(trifluoromethyl)benzyl)pyridin-2-yl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro[1,1′-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P′]palladium; palladium diacetate; caesium carbonate; In 1,4-dioxane; at 135℃; for 2.0h;Microwave irradiation; To a mixture of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (19.57 mg, 0.110 mmol), 2-chloro-6-(3- (trifluoromethyl)benzyl)pyridine (30 mg, 0.110 mmol), and 1,1 ‘-bis(di-tertbutylphosphino)ferrocene (5.787 mg, 12.15 p mol) in dioxane (0.6 mL) were added palladium (II) acetate (1.240 mg, 5.5 pmol) and cesium carbonate (53.97 mg, 0.166 mmol). The reaction was heated under microwave irradiation at 135C for 2 h. The mixture was concentrated. The residue was dissolved in DCM and extracted with water. The organic phase was concentrated. The residue was purified by column chromatography to give the title compound. LCMS m/z = 413.4 [M+1] ‘H NMR (400 MHz, CDC13): ppm 3.56 (t, J = 8 Hz, 2H), 3.90 (s, 3H), 4.02 (t, J = 8 Hz, 2H), 4.16 (s, 2H), 6.54(d, J= 8HZ, 1H), 6.68 (d, J= 8Hz, 1H), 7.11 (t, J= 8Hz, 1H), 7.40-7.58 (m, 5H), 7.63 (s, 1H), 8.30 (d, J= 8 Hz, 1H).
  • 32
  • [ 155135-61-8 ]
  • 3-chloro-5-(3-(trifluoromethyl)benzyl)pyridine [ No CAS ]
  • methyl 1-(5-(3-(trifluoromethyl)benzyl)pyridin-3-yl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro[1,1′-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P′]palladium; palladium diacetate; caesium carbonate; In 1,4-dioxane; at 65℃; for 3.0h;Microwave irradiation; To a mixture of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (0.130 g, 0.736 mmol), 3-chloro-5-(3- (trifluoromethyl)benzyl)pyridine (200 mg, 0.736 mmol), and 1,1 ‘-bis(di-tertbutylphosphino)ferrocene (38.58 mg, 80.98 pmol) in dioxane (3 mL) were added palladium (II) acetate (8.264 mg, 36.81 pmol), and cesium carbonate (0.360 g, 1.104 mmol). The reaction was heated under microwave irradiation at 135C for 2 h. The mixture was concentrated. The residue was purified by column chromatography to give the title compound. LCMS m/z = 413.4 [M+1].
  • 33
  • [ 155135-61-8 ]
  • 2-chloro-4-(3-fluoro-5-(trifluoromethyl)benzyl)pyridine [ No CAS ]
  • methyl 1-(4-(3-fluoro-5-(trifluoromethyl)benzyl)pyridin-2-yl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.3% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; palladium diacetate; caesium carbonate; In 1,4-dioxane; at 150℃; for 3.0h;Microwave irradiation; To a mixture of <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (0.264 g, 1.49 1 mmol), 2-chloro-4-(3- fluoro-5-(trifluoromethyl)benzyl)pyridine (432 mg, 1.491 mmol) and 1,1 ‘-bis(di-tertbutylphosphino)ferrocene (0.117 g, 0.246 mmol) in dioxane (15 mL) were added palladium (II) acetate (33.48 mg, 0.149 mmol), and cesium carbonate (0.972 g, 2.983 mmol). The reaction was heated under microwave irradiation at 150C for 3 h. The crude reaction mixture was filtered and concentrated. The resulting residue was purified by Biotage chromatography (20%-40% EtOAc/Hex) to give the title compound (21 mg, 48.79 pmol, 3.3 %) as a yellow solid. LCMS m/z431.2 [M+1] ‘H NMR (400 MHz, CDC13): ö ppm 3.58 (t, J= 8.60 Hz, 2H), 3.90 (s, 3H), 3.99 (s, 2H), 4.03 (t, J= 8.60 Hz, 2H), 6.52 (s, 1H), 6.61 (dd, J= 1.20, 5.20 Hz, 1H), 7.09 (d, J= 9.20 Hz, 1H), 7.21-7.29 (m, 3H), 7.52 (dd, J= 1.20, 8.00 Hz, 1H), 8.28 (d, J= 5.60 Hz, 1H), 8.51 (dd,0.8, 8.40 Hz, 1H).
  • 34
  • [ 155135-61-8 ]
  • 2-bromo-4-(3-fluoro-5-(trifluoromethyl)phenoxy)pyridine [ No CAS ]
  • methyl 1-(4-(3-fluoro-5-(trifluoromethyl)phenoxy)pyridin-2-yl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
45.7% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; palladium diacetate; caesium carbonate; In 1,4-dioxane; at 120℃; A mixture of 2-bromo-4-(3-fluoro-5-(trifluoromethyl)phenoxy)pyridine (99.6 mg, 0.296 mmol), <strong>[155135-61-8]methyl indoline-4-carboxylate</strong> (58 mg, 0.327 mmol), diacetoxypalladium (7.6 mg, 33.85 pmol), 1,1’-bis(di-tert-butylphosphino)ferrocene (327 mg, 0.692 mmol) (14.6 mg, 30.91 pmol), and cesium carbonate (260 mg, 0.798 mmol) in 3 mL dioxane was stirred at 120C (oil bath) overnight. The mixture was purified by HPLC (CH3CN/H20 gradient + 0.1% TFA). Fractions containing product were partly concentrated and residue was extracted with 1 M NaHCO3 and CH2C12. Organic phases were dried over MgSO4, filtered, and concentrated to give methyl 1 -(4-(3- fluoro-5-(trifluoromethyl)phenoxy)pyridin-2-yl)indoline-4-carboxylate (64.7 mg, 45.7 %) as a solid. LCMS m/z = 433.2 [M+1]. ‘H NMR (400 MHz, CDC13): ö ppm 3.59 (t, J= 8.5 Hz, 2H), 3.91 (s, 3H), 3.99 (t, J = 8.5 Hz, 2H), 6.33 (d, J = 2.0 Hz, 1H), 6.42 (dd, J, = 5.6 Hz, J2 = 2.0 Hz,1H), 6.99-7.03 (m, 1H), 7. 17-7.20 (m, 2H), 7.24-7.28 (m, 1H), 7.54 (dd, J, = 7.7 Hz, J2 = 1.0 Hz,1H), 8.29 (d, J = 5.7 Hz, 1H), 8.54 (dd, J, = 8.1 Hz, J2 = 0.7 Hz, 1H).
  • 35
  • [ 23814-14-4 ]
  • [ 155135-61-8 ]
  • methyl 1-(2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonyl)indoline-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% With 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; In methanol; at 20℃; for 4h; To a stirred solution of 2-oxo-2,3-dihydro-lH-benzo[d]imidazole-5-carboxylic acid56 150 mg) and methyl indoline-4-carboxylate114 (149 mg) in methanol (5 ml) was added 4-(4,6- dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride 115 (280 mg, DMTMM). The reaction muxture was stirred for 4 h at room temperature. LC/MS analysis indicated that the reaction was complete. The reaction mixture was concentrated in vacuo and the residue was purified by preparative reverse-phase HPLC (Gemini NX CI 8, 12 nm, 5mu, 100 x 30 mm, flow rate 40 ml/min, eluant: CH3CN/H2O containing formic acid) followed by lyophilisation in vacuo to afford methyl l-(2-oxo-2,3-dihydro-lH-benzo[d]imidazole-5-carbonyl)indoline-4-carboxylate (60 mg, 21%) as a white solid. MS (ISP): 338.1 ([M+H]+).
  • 36
  • [ 32315-10-9 ]
  • [ 155135-61-8 ]
  • C11H10ClNO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With pyridine; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; Under argon protection, bis (trichloromethyl) carbonate (150 mg, 0.5 mmol) was dissolved in 5 mL of tetrahydrofuran, cooled to 0 C, pyridine (79 mg, 1 mmol) was added, and the mixture was stirred for 10 minutes. -Methyl carboxylate 4a (177 mg, 1 mmol, prepared according to published patent application "WO 2016025933") was dissolved in 2 mL of a tetrahydrofuran solution, added dropwise to the solution, and reacted at room temperature overnight. 1N diluted hydrochloric acid was added dropwise to the reaction solution to adjust the pH to 4, 20 mL of ethyl acetate was added, and the mixture was washed with saturated sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 1- (chlorocarbonyl). Methyl indolin-4-carboxylic acid 4b (239 mg, white solid), yield: 100%.
  • 37
  • [ 155135-61-8 ]
  • 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2-fluorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylic acid [ No CAS ]
  • 38
  • [ 155135-61-8 ]
  • 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2-chlorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylic acid [ No CAS ]
  • 39
  • [ 155135-61-8 ]
  • 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2,6-difluorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylic acid [ No CAS ]
  • 40
  • [ 155135-61-8 ]
  • 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylic acid [ No CAS ]
  • 41
  • [ 155135-61-8 ]
  • methyl 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylate [ No CAS ]
  • 42
  • [ 155135-61-8 ]
  • methyl 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2-fluorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylate [ No CAS ]
  • 43
  • [ 155135-61-8 ]
  • methyl 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2-chlorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylate [ No CAS ]
  • 44
  • [ 155135-61-8 ]
  • methyl 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2,6-difluorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylate [ No CAS ]
  • 45
  • [ 155135-61-8 ]
  • methyl 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylate [ No CAS ]
  • 46
  • [ 155135-61-8 ]
  • 1-((1R,3S,5S)-3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)-1,2-oxazol-4-yl)methoxy)-8-azabicyclo(3.2.1)octane-8-carbonyl)isoindole-4-carboxylic acid [ No CAS ]
  • 47
  • [ 155135-61-8 ]
  • [ 135-19-3 ]
  • methyl 1-(naphthalen-2-yl)-1H-indole-4-carboxylate [ No CAS ]
  • 48
  • [ 155135-61-8 ]
  • methyl 6-(2-methylprop-1-en-1-yl)-6-phenyl-1,2-dihydro-6H-benzo[4,5]imidazo[2,1-b]pyrrolo[3,2,1-ij]quinazoline-3-carboxylate [ No CAS ]
  • 49
  • [ 155135-61-8 ]
  • methyl 4-phenyl-5-(propan-2-ylidene)-4,5,13,14-tetrahydrobenzo[4',5']imidazo[2',1':2,3][1,3]diazepino[6,7,1-hi]indole-1-carboxylate [ No CAS ]
  • 50
  • [ 4857-06-1 ]
  • [ 155135-61-8 ]
  • methyl 1-(1H-benzo[d]imidazol-2-yl)indoline-4-carboxylate [ No CAS ]
  • 51
  • [ 155135-61-8 ]
  • (2-chloropyrimidin-4-yl)(3-fluoro-5-(trifluoromethyl)phenyl)methanone [ No CAS ]
  • methyl 1-(4-(3-fluoro-5-(trifluoromethyl)benzoyl)pyrimidin-2-yl)indoline-4-carboxylate [ No CAS ]
  • 52
  • [ 3934-20-1 ]
  • [ 155135-61-8 ]
  • methyl 1-(2-chloropyrimidin-4-yl)indoline-4-carboxylate [ No CAS ]
  • 53
  • [ 155135-61-8 ]
  • [ 1837-55-4 ]
  • methyl 1-(5-chloropyridazin-3-yl)indoline-4-carboxylate [ No CAS ]
  • 54
  • [ 1193-21-1 ]
  • [ 155135-61-8 ]
  • methyl 1-(6-chloropyrimidin-4-yl)indoline-4-carboxylate [ No CAS ]
  • 55
  • [ 155135-61-8 ]
  • 1-(2-(3-fluoro-5-(trifluoromethyl)benzyl)pyrimidin-4-yl)-N-(2-hydroxyethyl)indoline-4-carboxamide [ No CAS ]
  • 56
  • [ 155135-61-8 ]
  • N-(2-hydroxyethyl)-1-(6-(3-methylbenzyl)pyrimidin-4-yl)indoline-4-carboxamide [ No CAS ]
  • 57
  • [ 155135-61-8 ]
  • methyl 1-(6-(3-(trifluoromethyl)phenoxy)pyrimidin-4-yl)indoline-4-carboxylate [ No CAS ]
  • 58
  • [ 155135-61-8 ]
  • methyl 1-(6-((3-(trifluoromethyl)phenyl)thio)pyrimidin-4-yl)indoline-4-carboxylate [ No CAS ]
  • 59
  • [ 155135-61-8 ]
  • 1-(6-(3-fluorobenzyl)pyrimidin-4-yl)-N-(2-hydroxyethyl)indoline-4-carboxamide [ No CAS ]
  • 60
  • [ 155135-61-8 ]
  • 1-(6-(3,5-dimethylbenzyl)pyrimidin-4-yl)-N-(2-hydroxyethyl)indoline-4-carboxamide [ No CAS ]
  • 61
  • [ 155135-61-8 ]
  • C23H17F3N4O2 [ No CAS ]
  • 62
  • [ 155135-61-8 ]
  • C23H17F3N4O2 [ No CAS ]
  • 63
  • [ 155135-61-8 ]
  • C23H17F3N4O2 [ No CAS ]
  • 64
  • [ 155135-61-8 ]
  • C23H20N4O2 [ No CAS ]
  • 65
  • [ 155135-61-8 ]
  • C22H17FN4O2 [ No CAS ]
  • 66
  • [ 155135-61-8 ]
  • 1-(6-(3,5-difluorobenzyl)pyrimidin-4-yl)-N-(2-hydroxyethyl)indoline-4-carboxamide [ No CAS ]
  • 67
  • [ 155135-61-8 ]
  • C24H22N4O2 [ No CAS ]
  • 68
  • [ 155135-61-8 ]
  • C22H16F2N4O2 [ No CAS ]
  • 69
  • [ 155135-61-8 ]
  • C23H17F3N4O3 [ No CAS ]
  • 70
  • [ 155135-61-8 ]
  • C23H20N4O3 [ No CAS ]
  • 71
  • [ 155135-61-8 ]
  • C24H22N4O4 [ No CAS ]
  • 72
  • [ 155135-61-8 ]
  • C22H18N4O2 [ No CAS ]
  • 73
  • [ 155135-61-8 ]
  • N-(2-hydroxyethyl)-1-(6-(3-(trifluoromethoxy)benzyl)pyrimidin-4-yl)indoline-4-carboxamide [ No CAS ]
  • 74
  • [ 155135-61-8 ]
  • C21H13F4N3O3 [ No CAS ]
  • 75
  • [ 155135-61-8 ]
  • C21H13F4N3O3 [ No CAS ]
  • 76
  • [ 155135-61-8 ]
  • C21H14F3N3O3 [ No CAS ]
  • 77
  • [ 155135-61-8 ]
  • C22H17F4N3O3 [ No CAS ]
  • 78
  • [ 155135-61-8 ]
  • C22H17F4N3O3 [ No CAS ]
  • 79
  • [ 155135-61-8 ]
  • C22H18F3N3O3 [ No CAS ]
  • 80
  • [ 155135-61-8 ]
  • C20H15F3N4O2 [ No CAS ]
  • 81
  • [ 155135-61-8 ]
  • C20H14F3N3O3 [ No CAS ]
  • 82
  • [ 155135-61-8 ]
  • N-(2-hydroxyethyl)-1-(6-(3-methoxybenzyl)pyrimidin-4-yl)-indoline-4-carboxamide [ No CAS ]
  • 83
  • [ 155135-61-8 ]
  • C20H14F3N3O2S [ No CAS ]
  • 84
  • [ 155135-61-8 ]
  • 1-(6-(3,5-dimethoxybenzyl)pyrimidin-4-yl)-N-(2-hydroxyethyl)indoline-4-carboxamide [ No CAS ]
  • 85
  • [ 155135-61-8 ]
  • 1-(6-benzylpyrimidin-4-yl)-N-(2-hydroxyethyl)indoline-4-carboxamide [ No CAS ]
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