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[ CAS No. 243467-60-9 ] {[proInfo.proName]}

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Chemical Structure| 243467-60-9
Chemical Structure| 243467-60-9
Structure of 243467-60-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 243467-60-9 ]

CAS No. :243467-60-9 MDL No. :MFCD26386298
Formula : C15H10FNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :OHQPVSORYCUZRN-UHFFFAOYSA-N
M.W : 255.24 Pubchem ID :22603071
Synonyms :

Calculated chemistry of [ 243467-60-9 ]

Physicochemical Properties

Num. heavy atoms : 19
Num. arom. heavy atoms : 15
Fraction Csp3 : 0.0
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 70.19
TPSA : 42.23 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.52 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.27
Log Po/w (XLOGP3) : 3.29
Log Po/w (WLOGP) : 3.89
Log Po/w (MLOGP) : 3.17
Log Po/w (SILICOS-IT) : 2.84
Consensus Log Po/w : 3.09

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.85

Water Solubility

Log S (ESOL) : -3.95
Solubility : 0.0288 mg/ml ; 0.000113 mol/l
Class : Soluble
Log S (Ali) : -3.85
Solubility : 0.0359 mg/ml ; 0.000141 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.63
Solubility : 0.00596 mg/ml ; 0.0000233 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 1.57

Safety of [ 243467-60-9 ]

Signal Word:Warning Class:
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 UN#:
Hazard Statements:H315-H319 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 243467-60-9 ]

* 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 [ 243467-60-9 ]

[ 243467-60-9 ] Synthesis Path-Downstream   1~40

  • 1
  • [ 138900-18-2 ]
  • [ 243467-60-9 ]
YieldReaction ConditionsOperation in experiment
96% With potassium hydroxide; water In ethanol for 24h; Heating;
With potassium hydroxide In ethanol; water 10 EXAMPLE 10 EXAMPLE 10 1-(4-Fluorophenyl)-5-hydoxymethyl-1H-indole (10a) A solution of 5-cyano-1-(4-fluorophenyl)-1H-indole (43.2 g) (prepared as described by Perregaard et al. J. Med. Chem. 1992 35, 1092-1101) and potassium hydroxide (43.1 g) in 90% aqueous ethanol (500 mL) was boiled at reflux for 5 days. The solvents were evaporated in vacuo and water (300 mL) was added. The resulting slurry was acidified with concentrated hydrochloric acid. The precipitated 1-(4-fluorophenyl)-1H-indol-5-carboxylic acid (33.5 g) was collected by filtration and dried in vacuo and used without further purification: 1H NMR (DMSO-d6) δ 6.85 (d, 1H), 7.45 (t, 2H), 7.55 (d, 1H), 7.65 (dd, 2H), 7.75 (d, 1H), 7.80 (broad d, 1H), 8.10 (broad s, 1H).
  • 2
  • [ 124-40-3 ]
  • [ 243467-60-9 ]
  • [ 330944-13-3 ]
YieldReaction ConditionsOperation in experiment
52% Stage #1: (1-(4-fluorophenyl)-1H-indole-5-carboxylic acid) With chloroformic acid ethyl ester; triethylamine In dichloromethane at -30 - -10℃; for 2h; Stage #2: dimethyl amine In ethanol; dichloromethane at -10 - 20℃;
  • 3
  • [ 74-89-5 ]
  • [ 243467-60-9 ]
  • [ 330944-14-4 ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: (1-(4-fluorophenyl)-1H-indole-5-carboxylic acid) With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 0.833333h; Stage #2: methylamine In tetrahydrofuran at 0 - 20℃; for 1.08333h;
  • 4
  • [ 243467-60-9 ]
  • [ 243467-59-6 ]
YieldReaction ConditionsOperation in experiment
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating;
  • 5
  • [ 243467-60-9 ]
  • [ 243467-63-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C
  • 6
  • [ 243467-60-9 ]
  • [ 243467-64-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C
  • 7
  • [ 243467-60-9 ]
  • [ 243467-62-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 1.5 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C
  • 8
  • [ 243467-60-9 ]
  • [ 243467-61-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 3.7 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C
  • 9
  • [ 243467-60-9 ]
  • [ 243467-65-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating
  • 10
  • [ 243467-60-9 ]
  • [ 330944-19-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: ethyl chloroformate; NEt3 / CH2Cl2 / 2 h / -30 - -10 °C 1.2: 52 percent / CH2Cl2; ethanol / -10 - 20 °C 2.1: 92 percent / TFA / acetic acid / 1 h / Heating 3.1: 86 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr 4.1: lithium aluminum hydride / tetrahydrofuran / 2 h / 40 °C
  • 11
  • [ 243467-60-9 ]
  • [ 330944-16-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: ethyl chloroformate; NEt3 / CH2Cl2 / 2 h / -30 - -10 °C 1.2: 52 percent / CH2Cl2; ethanol / -10 - 20 °C 2.1: 92 percent / TFA / acetic acid / 1 h / Heating
  • 12
  • [ 243467-60-9 ]
  • [ 330944-18-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: ethyl chloroformate; NEt3 / CH2Cl2 / 2 h / -30 - -10 °C 1.2: 52 percent / CH2Cl2; ethanol / -10 - 20 °C 2.1: 92 percent / TFA / acetic acid / 1 h / Heating 3.1: 86 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr
  • 13
  • [ 243467-60-9 ]
  • [ 330944-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.83 h / 20 °C 1.2: 73 percent / tetrahydrofuran / 1.08 h / 0 - 20 °C 2.1: 100 percent / TFA / acetic acid / 1.5 h / Heating 3.1: 58 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr
  • 14
  • [ 243467-60-9 ]
  • [ 330944-15-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.83 h / 20 °C 1.2: 73 percent / tetrahydrofuran / 1.08 h / 0 - 20 °C 2.1: 100 percent / TFA / acetic acid / 1.5 h / Heating
  • 15
  • [ 243467-60-9 ]
  • [ 243467-23-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 1.5 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C 6: TFA / acetic acid / 1 h / Heating
  • 16
  • [ 243467-60-9 ]
  • [ 243467-24-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 3.7 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C 6: TFA / acetic acid / 1 h / Heating
  • 17
  • [ 243467-60-9 ]
  • 1-[2-[4-[5-Dimethylaminomethyl-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]ethyl]-2-imidazolidinon [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: ethyl chloroformate; NEt3 / CH2Cl2 / 2 h / -30 - -10 °C 1.2: 52 percent / CH2Cl2; ethanol / -10 - 20 °C 2.1: 92 percent / TFA / acetic acid / 1 h / Heating 3.1: 86 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr 4.1: lithium aluminum hydride / tetrahydrofuran / 2 h / 40 °C 5.1: 21 percent / K2CO3; KI / various solvent(s) / 8 h / Heating
  • 18
  • [ 243467-60-9 ]
  • 1-[2-[4-[1-(4-Fluorophenyl)-5-methylaminomethyl-1H-indol-3-yl]-1-piperidinyl]ethyl]-2-imidazolidinon [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.83 h / 20 °C 1.2: 73 percent / tetrahydrofuran / 1.08 h / 0 - 20 °C 2.1: 100 percent / TFA / acetic acid / 1.5 h / Heating 3.1: 58 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr 4.1: 59 percent / K2CO3; KI / various solvent(s) / 8 h / Heating 5.1: 16 percent / lithium aluminum hydride / tetrahydrofuran / 3 h / Heating
  • 19
  • [ 243467-60-9 ]
  • [ 330944-21-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.83 h / 20 °C 1.2: 73 percent / tetrahydrofuran / 1.08 h / 0 - 20 °C 2.1: 100 percent / TFA / acetic acid / 1.5 h / Heating 3.1: 58 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr 4.1: 59 percent / K2CO3; KI / various solvent(s) / 8 h / Heating
  • 20
  • [ 243467-60-9 ]
  • N,N-Dimethyl-1-(4fluorophenyl)-3-[1-[2-(2-imidazolidinon-1-yl)ethyl]-4-piperidinyl]-1H-indole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: ethyl chloroformate; NEt3 / CH2Cl2 / 2 h / -30 - -10 °C 1.2: 52 percent / CH2Cl2; ethanol / -10 - 20 °C 2.1: 92 percent / TFA / acetic acid / 1 h / Heating 3.1: 86 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr 4.1: 29 percent / K2CO3; KI / various solvent(s) / 8 h / Heating
  • 21
  • [ 243467-60-9 ]
  • [ 243467-32-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 3.7 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C 6: TFA / acetic acid / 1 h / Heating 7: 57 percent / K2CO3; KI / various solvent(s) / 8 h / Heating
  • 22
  • [ 243467-60-9 ]
  • [ 243467-31-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 1.5 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C 6: TFA / acetic acid / 1 h / Heating 7: 1.6 g / K2CO3; KI / various solvent(s) / 8 h / Heating
  • 23
  • [ 243467-60-9 ]
  • 1-(2-{4-[1-(4-fluorophenyl)-5-[(1-methyl-1H-1,2,3,4-tetrazol-5-yl)methyl]-1H-indol-3-yl]-1-piperidinyl}ethyl)-2-imidazolidinone 2.5-fumarate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 1.5 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C 6: TFA / acetic acid / 1 h / Heating 7: 1.6 g / K2CO3; KI / various solvent(s) / 8 h / Heating 8: 17 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr
  • 24
  • [ 243467-60-9 ]
  • 1-(2-{4-[1-(4-fluorophenyl)-5-[(2-methyl-2H-1,2,3,4-tetrazol-5-yl)methyl]-1H-indol-3-yl]-1-piperidinyl}ethyl)-2-imidazolidinone 2.25-fumarate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: lithium aluminum hydride / tetrahydrofuran / 2 h / Heating 2: methanesulfonyl chloride; NEt3 / CH2Cl2 / 2 h / 0 - 5 °C 3: 8.2 g / dimethylsulfoxide / 0.67 h / 80 °C 4: sodium azide; NEt3*HCl / 1,2-dimethoxy-ethane / 48 h / Heating 5: 3.7 g / potassium tert-butoxide / 1-methyl-pyrrolidin-2-one / 0 - 20 °C 6: TFA / acetic acid / 1 h / Heating 7: 57 percent / K2CO3; KI / various solvent(s) / 8 h / Heating 8: 22 percent / H2 / PtO2 / acetic acid; trifluoroacetic acid / 5 h / 20 °C / 2206.52 Torr
  • 25
  • [ 1144523-66-9 ]
  • [ 243467-60-9 ]
YieldReaction ConditionsOperation in experiment
97% With water; lithium hydroxide In tetrahydrofuran at 55℃; for 18h; E E. To a 3-L 4-neck flask equipped with mechanical stirrer, N2 inlet, condenser and thermocouple was added compound 2d (58.0 g, 0.215 mol), THF (0.58 L), deionized water (0.58 L) and lithium hydroxide (20.63 g, 0.86 mol). The reaction mixture was warmed to 55 °C for 18 h. The reaction was cooled to room temperature and the pH was adjusted to ~3 with 1M HC1 (-0.8 L). A white precipitate formed during pH adjustment. The thick white slurry was filtered and washed with deionized water (0.3 L). The white solid was dried in vacuo at 45 °C to give compound 2e (53.5 g, 97%). 1H NMR (Chloroform-d) δ: 8.54 (s, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.48 (d, J = 8.8 Hz, 3H), 7.36 (d, J = 2.9 Hz, 1H), 7.23 - 7.32 (m, 2H), 6.81 (d, 1H).
97% With lithium hydroxide In tetrahydrofuran; water at 55℃; for 18h; Inert atmosphere; 3.E E. To a 3-L 4-neck flask equipped with mechanical stirrer, N2 inlet, condenser and thermocouple was added compound 1c (58.0 g, 0.2 15 mol), THF (0.58 L), deionized water (0.58 L) and lithium hydroxide (20.63 g, 0.86 mol). The reaction mixture was warmed to 55 °C for 18 h. The reaction was cooled to room temperature and the pH was adjusted to ~3 with 1 M HCl (-0. 8 L). A white precipitate formed during pH adjustment. The thick white slurry was filtered and washed with deionized water (0.3 L). The white solid was dried in vacuo at 45 °C to give compound id (53.5 g, 97 %). 1H NMR (Chloroform-d) δ: 8.54 (s, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.48 (d, J = 8.8 Hz, 3H), 7.36 (d, J = 2.9 Hz, 1H), 7.23 - 7.32 (m, 2H), 6.81 (d, 1H).
Stage #1: methyl 1-(4-fluorophenyl)-1H-indole-5-carboxylate With lithium hydroxide monohydrate; water In tetrahydrofuran at 20℃; for 120h; Stage #2: With hydrogenchloride In tetrahydrofuran; water 1a.I A mixture of methyl l-(4- fluorophenyl)-indole-5-carboxylate Im (0.58 g, 2.15 mmol) and LiOH H2O (0.36 g, 8.6 mmol) in THF (15 mL) and H2O (10 mL) was stirred at room temperature for 5 days. Aqueous 10% HCl solution was added to the reaction mixture to adjust pH = 3 ~ 4. The resulting mixture was extracted with EtOAc (2x). The organic solution was washed with aq. NaCl, dried over Na2SO4 and concentrated to give In (0.5 g).
Stage #1: methyl 1-(4-fluorophenyl)-1H-indole-5-carboxylate With lithium hydroxide monohydrate; water In tetrahydrofuran at 20℃; for 120h; Stage #2: With hydrogenchloride In tetrahydrofuran; water 7.B B. 1-(4-fluorophenyl)-indole-5-carboxylic acid, 7d. A mixture of methyl 1-(4-fluorophenyl)-indole-5-carboxylate 7c (0.58 g, 2.15 mmol) and LiOH.H2O (0.36 g, 8.6 mmol) in THF (15 mL) and H2O (10 mL) was stirred at room temperature for 5 days. Aqueous 10% HCl solution was added to the reaction mixture to adjust pH=34. The resulting mixture was extracted with EtOAc (2×). The organic solution was washed with aq. NaCl, dried over Na2SO4 and concentrated to give 7d (0.5 g).
Stage #1: methyl 1-(4-fluorophenyl)-1H-indole-5-carboxylate With lithium hydroxide monohydrate; water In tetrahydrofuran at 20℃; for 120h; Stage #2: With hydrogenchloride In tetrahydrofuran; water 3A.I A mixture of methyl 1-(4-fluorophenyl)-indole-5-carboxylate 3g (0.58 g, 2.15 mmol) and LiOH H2O (0.36 g, 8.6 mmol) in THF (15 mL) and H2O (10 mL) was stirred at room temperature for 5 days. Aqueous 10% HCl solution was added to the reaction mixture to adjust pH=34. The resulting mixture was extracted with EtOAc (2×). The organic solution was washed with aq. NaCl, dried over Na2SO4 and concentrated to give 3h (0.5 g).
0.5 g Stage #1: methyl 1-(4-fluorophenyl)-1H-indole-5-carboxylate With lithium hydroxide monohydrate In tetrahydrofuran; water at 20℃; for 120h; Stage #2: With hydrogenchloride In tetrahydrofuran; water 7.B B. 1-(4-Fluorophenyl)-indole-5-carboxylic acid, 7d A mixture of methyl 1-(4-fluorophenyl)-indole-5-carboxylate 7c (0.58 g, 2.15 mmol) and LiOH H2O (0.36 g, 8.6 mmol) in THF (15 mL) and H2O (10 mL) was stirred at room temperature for 5 days. Aqueous 10% HCl solution was added to the reaction mixture to adjust pH=3 4. The resulting mixture was extracted with EtOAc (2*). The organic solution was washed with aq. NaCl, dried over Na2SO4 and concentrated to give 0.5 g of compound 7d. MS m/z 256.2 (M+H+).
294.6 mg With water; lithium hydroxide In tetrahydrofuran at 55℃; for 18h; (l-(4-Fluorophenyl)-lH-indole-5-carboxylic acid) Methyl l-(4-fluorophenyl)-lH-indole-5-carboxylate (330mg, 1.23 mmol) was dissolved in THF (3.06 mL), whereupon 0 (3.06 mL) was added. To this solution, LiOH (117 mg, 4.9 mmol) was added and the reaction mixture was heated to 55°C for 18 hrs. After this, the reaction mixture was adjusted to a pH of approx. 3, whereupon the formation of a white solid was noted. This white slurry was filtered off and washed with 0, before being dried in vacuo to remove excess 0, yielding a white powder (294.6 mg, 1.15 mmol). 'H NMR (300 MHz, DMSO-d6) δ 12.61 (br s, IH), 8.33 (d, J=1.21 Hz, IH), 7.81 (dd, J=1.61, 8.86 Hz, IH), 7.74 (d, J=3.43 Hz, IH), 7.63-7.69 (m, 2H), 7.53 (d, J=8.86 Hz, 1H), 7.40-7.48 (m, 2H), 6.85 (dd, J=0.60, 3.43 Hz, 1H). MS (ESI): m/z = 256.1 [M+H]+.

  • 26
  • [ 1011-65-0 ]
  • [ 460-00-4 ]
  • [ 243467-60-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: potassium carbonate / copper(l) iodide / 2.5 h / 220 °C / Microwave 2.1: water; lithium hydroxide monohydrate / tetrahydrofuran / 120 h / 20 °C 2.2: pH 3 - 4
Multi-step reaction with 2 steps 1.1: potassium carbonate; copper(l) iodide / 2.5 h / 220 °C / microwave irradiation 2.1: water; lithium hydroxide monohydrate / tetrahydrofuran / 120 h / 20 °C 2.2: pH 3 - 4
  • 27
  • (4-(azetidin-3-yl)piperazin-1-yl)(thiazol-2-yl)methanone dihydrochloride [ No CAS ]
  • [ 243467-60-9 ]
  • [ 1252777-85-7 ]
YieldReaction ConditionsOperation in experiment
94% With triethylamine; HATU In dichloromethane at 20℃; for 72h; F F. To a 5-L 4-neck flask equipped with mechanical stirrer, N2 inlet, condenser and thermocouple was added compound 2e (105.0 g, 0.41 mol), CH2C12 (1.58 L), Et3N (0.344 L, 2.47 mol), (4-(azetidin-3-yl)piperazin-l-yl)(thiazol-2-yl)methanone dihydrochloride (cpd le, 133.8 g, 0.41 mol) and HATU (156.4 g, 0.41 mol). The reaction was stirred for 72 h at room temperature. The reaction solution was transferred to a 22-L extractor containing CH2CI2 (4 L) and sat NaHC03 (2 L). The organic layer was washed with brine (2 L), dried (NaS04), filtered and evaporated to dryness. The residue was purified by column chromatography (5 Kg Biotage S1O2 column, 3 column volumes CH2CI2, 10 column volumes 3% MeOH/CH2Cl2) to give 189 g (94%) of compound 1 as its free base. The free base of compound 1 exhibited an onset melting temperature of about 158.09°C and a peak temperature of melting of about 187.15°C. 1H NMR (MeOD) δ: 7.99 (s, 1H), 7.93 (d, J = 3.4 Hz, 1H), 7.81 (d, J = 3.2 Hz, 1H), 7.44 - 7.62 (m, 5H), 7.23 - 7.39 (m, 2H), 6.77 (d, J = 3.4 Hz, 1H), 4.43 - 4.53 (m, 1H), 4.39 (br. s., 1H), 4.17 - 4.34 (m, 2H), 4.06 (dd, J = 10.0, 4.9 Hz, 1H), 3.80 (br. s., 1H), 3.28 - 3.38 (m, 2H), 3.18 - 3.28 (m, 1H), 2.50 (br. s., 4H).
  • 28
  • [ 1011-65-0 ]
  • [ 243467-60-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: trans-N,N'-dimethylcyclohexane-1,2-diamine; copper(l) iodide; tripotassium phosphate "n" hydrate / toluene / 16 h / 85 °C 2: lithium hydroxide; water / tetrahydrofuran / 18 h / 55 °C
Multi-step reaction with 2 steps 1: potassium carbonate; copper(l) iodide / 2.5 h / 220 °C / Microwave irradiation 2: lithium hydroxide / tetrahydrofuran; water / 18 h / 55 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: trans-N,N'-dimethylcyclohexane-1,2-diamine; tripotassium phosphate "n" hydrate; copper(l) iodide / toluene / 16 h / 85 °C / Inert atmosphere 2: lithium hydroxide / tetrahydrofuran; water / 18 h / 55 °C / Inert atmosphere
Multi-step reaction with 2 steps 1.1: copper(l) iodide; potassium carbonate / 2.5 h / 220 °C / Microwave irradiation 2.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 120 h / 20 °C 2.2: pH 3-4

  • 29
  • [ 352-34-1 ]
  • [ 243467-60-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: trans-N,N'-dimethylcyclohexane-1,2-diamine; copper(l) iodide; tripotassium phosphate "n" hydrate / toluene / 16 h / 85 °C 2: lithium hydroxide; water / tetrahydrofuran / 18 h / 55 °C
Multi-step reaction with 2 steps 1: trans-N,N'-dimethylcyclohexane-1,2-diamine; tripotassium phosphate "n" hydrate; copper(l) iodide / toluene / 16 h / 85 °C / Inert atmosphere 2: lithium hydroxide / tetrahydrofuran; water / 18 h / 55 °C / Inert atmosphere
  • 30
  • [ 1373356-64-9 ]
  • [ 243467-60-9 ]
  • [ 1373356-16-1 ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: (4-(azetidin-3-yl)piperidin-1-yl)(thiazol-2-yl)methanone; (1-(4-fluorophenyl)-1H-indole-5-carboxylic acid) With triethylamine In dichloromethane at 20℃; for 0.333333h; Stage #2: With HATU In dichloromethane at 20℃; for 20h; 7.C C. 1-(4-Fluorophenyl)-5-({3-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]azetidin-1-yl}carbonyl)-1H-indole, Cpd 30 To a stirring solution of compound 1j (0.40 mmol, 100 mg) and compound 7d (0.44 mmol, 110 mg) in 4 mL of CH2Cl2 was added Et3N (1.59 mmol, 0.22 mL). After 20 min at 20° C., HATU (0.48 mmol, 180 mg) was added and the mixture was stirred at 20° C. for 20 h. The solvent was removed and the crude residue was purified by preparative reverse-phase chromatography to give 165 mg (85% yield) of Cpd 30. 1H NMR (CD3OD, 400 MHz): δ=7.99 (s, 1H), 7.92 (br. s., 1H), 7.79 (d, J=3.2 Hz, 1H), 7.44-7.58 (m, 5H), 7.30 (t, J=8.7 Hz, 2H), 6.77 (d, J=3.4 Hz, 1H), 5.28 (br. s., 1H), 4.53-4.69 (m, 1H), 4.39-4.51 (m, 1H), 4.10-4.29 (m, 2H), 3.95 (br. s., 1H), 3.10-3.27 (m, 1H), 2.89 (t, J=10.5 Hz, 1H), 2.33-2.56 (m, 1H), 1.65-1.98 (m, J=10.8 Hz, 3H), 1.19 (br. s., 2H). MS m/z 489.1 (M+H+).
  • 31
  • [ 460-00-4 ]
  • [ 243467-60-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate; copper(l) iodide / 2.5 h / 220 °C / Microwave irradiation 2: lithium hydroxide / tetrahydrofuran; water / 18 h / 55 °C / Inert atmosphere
Multi-step reaction with 2 steps 1.1: copper(l) iodide; potassium carbonate / 2.5 h / 220 °C / Microwave irradiation 2.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 120 h / 20 °C 2.2: pH 3-4
  • 32
  • [ 243467-60-9 ]
  • [ 1429022-29-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine; HATU / dichloromethane / 16 h / 20 °C 2: triethylamine / methanol / 96 h
  • 33
  • [ 243467-60-9 ]
  • [ 1252765-13-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine; HATU / dichloromethane / 16 h / 20 °C 2: triethylamine / methanol / 96 h 3: triethylamine; HATU / dichloromethane / 16 h / 20 °C
  • 34
  • [ 243467-60-9 ]
  • [ 1429022-30-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: triethylamine; HATU / dichloromethane / 16 h / 20 °C 2: triethylamine / methanol / 96 h 3: triethylamine; HATU / dichloromethane / 16 h / 20 °C 4: hydrogenchloride / dichloromethane; water / 1 h / Inert atmosphere
  • 35
  • [ 1252779-86-4 ]
  • [ 243467-60-9 ]
  • [ 1252765-77-7 ]
YieldReaction ConditionsOperation in experiment
290 mg With triethylamine; HATU In dichloromethane at 20℃; for 16h; 2.E E. 2,2,2-Trifluoro-1-(4-(1-(1-(4-fluorophenyl)-1H-indole-5- carbonyl)azetidin-3-yl)piperazin-1-yl)ethanone, 2h. A mixture of 2g (240 mg, 0.77mmol), id (178 mg, 0.70 mmol), Et3N (0.58 mL, 4.2 mmol), and HATU (294 mg, 0.77 mmol) in CH2C12 (7 mL) was stirred at room temperature for 16 h. The reaction mixture was diluted with ethyl ether, washed with aq NaHCO3 and aq NaC1, dried over Na2SO4 and concentrated. Purification by flash column chromatography (silica gel, 3% MeOH/CH2C12) gave 2h (290 mg).
  • 36
  • (4-(azetidin-3-yl)piperazin-1-yl)(thiazol-2-yl)methanone dihydrochloride [ No CAS ]
  • [ 243467-60-9 ]
  • [ 1252765-13-1 ]
YieldReaction ConditionsOperation in experiment
94% With triethylamine; HATU In dichloromethane at 20℃; for 72h; Inert atmosphere; 3.F F. To a 5-L 4-neck flask equipped with mechanical stirrer, N2 inlet, condenser and thermocouple was added compound 1d (105.0 g, 0.41 mol), CH2Cl2 (1.58 L), Et3N (0.344 L, 2.47 mol), (4-(azetidin-3-yl)piperazin-1-yl)(thiazol-2-yl)methanone dihydrochloride (cpd 3d, 133.8 g, 0.41 mol) and HATU (156.4 g, 0.41 mol). The reaction was stirred for 72 h at room temperature. The reaction solution was transferred to a 22-L extractor containing CH2Cl2 (4 L) and sat NaHCO3 (2L). The organic layer was washed with brine (2L), dried (NaSO4), filtered and evaporated to dryness. The residue was purified by column chromatography (5 Kg Biotage SiO2 column, 3 column volumes CH2Cl2, 10 column volumes 3% MeOH/CH2Cl2) to give 189 g (94 %) of compound 1 as its free base. 1H NMR (MeOD) δ: 7.99 (s, 1H), 7.93 (d,J = 3.4 Hz, 1H), 7.81 (d, J = 3.2 Hz, 1H), 7.44 - 7.62 (m, 5H), 7.23 - 7.39 (m, 2H), 6.77 (d, J = 3.4 Hz, 1H), 4.43 -4.53 (m, 1H), 4.39 (br. s., 1H), 4.17 -4.34 (m, 2H), 4.06 (dd, J = 10.0, 4.9 Hz, 1H), 3.80 (br. s., 1H), 3.28 - 3.38 (m, 2H), 3.18 - 3.28 (m, 1H), 2.50 (br. s., 4H).
  • 37
  • (4-(azetidin-3-yl)piperazin-1-yl)(thiazol-2-yl)methanone dihydrochloride [ No CAS ]
  • [ 243467-60-9 ]
  • [ 1429022-30-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine; HATU / dichloromethane / 72 h / 20 °C / Inert atmosphere 2: hydrogenchloride / dichloromethane; water / 1 h / Inert atmosphere
  • 38
  • [ 352-34-1 ]
  • [ 1011-65-0 ]
  • [ 243467-60-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; copper(l) iodide / toluene / 21 h / 85 °C 2: water; lithium hydroxide / tetrahydrofuran / 18 h / 55 °C
  • 40
  • 2-(4-(azetidin-3-yl)piperazin-1-yl)pyrimidine hydrochloride [ No CAS ]
  • [ 243467-60-9 ]
  • (1-(4-fluorophenyl)-1H-indol-5-yl)(3-(4-(pyrimidin-2-yl)piperazin-1-yl)azetidin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% With 4-methyl-morpholine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate In tetrahydrofuran at 20℃; for 12h;
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