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[ CAS No. 387827-18-1 ] {[proInfo.proName]}

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Chemical Structure| 387827-18-1
Chemical Structure| 387827-18-1
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Product Details of [ 387827-18-1 ]

CAS No. :387827-18-1 MDL No. :MFCD24465705
Formula : C16H22N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :HPSJZYBXANBFJH-UHFFFAOYSA-N
M.W : 274.36 Pubchem ID :22049056
Synonyms :

Calculated chemistry of [ 387827-18-1 ]

Physicochemical Properties

Num. heavy atoms : 20
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.44
Num. rotatable bonds : 4
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 85.8
TPSA : 55.56 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.34 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.05
Log Po/w (XLOGP3) : 2.3
Log Po/w (WLOGP) : 2.92
Log Po/w (MLOGP) : 2.36
Log Po/w (SILICOS-IT) : 2.04
Consensus Log Po/w : 2.54

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.95
Solubility : 0.309 mg/ml ; 0.00113 mol/l
Class : Soluble
Log S (Ali) : -3.1
Solubility : 0.216 mg/ml ; 0.000786 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.41
Solubility : 0.106 mg/ml ; 0.000386 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.19

Safety of [ 387827-18-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 387827-18-1 ]

* 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.

  • Upstream synthesis route of [ 387827-18-1 ]
  • Downstream synthetic route of [ 387827-18-1 ]

[ 387827-18-1 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 138647-49-1 ]
  • [ 387827-18-1 ]
YieldReaction ConditionsOperation in experiment
81% With sodium carbonate; lithium chloride In 1,2-dimethoxyethane; water for 3 h; Heating / reflux A degassed mixture of 2.0 M aqueous [NA2CO3] solution (4.20 mL), tert-butyl [4-[(TRIFLUOROMETHYL)] sulfonyl] [OXY}-3,] 6-dihydro-1 (2H) -pyridine carboxylate (0.500 g, 1. 51 mmol), 3-aminophenylboronic acid [HEMISULFATE] (0.393 g, 2.11 mmol), lithium chloride (0.191 g, 4.50 mmol) and tetrakis-triphenylphosphine palladium (0.080 g, 0.075 mmol) in dimethoxyethane (5.00 mL) was heated at reflux temperature for 3 hours under Argon. The organic layer of the cooled reaction mixture was separated and the aqueous layer was washed with ethyl acetate (3 x 50 [ML).] The combined organic solutions were dried and concentrated in vacuo. The crude product was chromatographed (silica, hexanes: EtOAc: dichloromethane 6: 1: 1 with [1percent] isopropylamine) to give the desired product (0.330 g, [81percent). 1H] NMR (400 MHz, [CDC13)] 8 7.12 (t, [1H,] J = 7. [60] Hz), 6. [78] (d, 1H, J = 8.4 Hz), 6. [69] (t, 1H, J =. [2.] 0 Hz), 6.59 (dd, 1H, J = 2.2, 8.0 Hz), 6.01 (br, 1H), 4.10- 4.01 (d, 2H, J = 2.4 Hz), 3.61 (t, 2H, J [= 5.] 6 Hz), 2.52- 2.46 (m, 2H), 1.49 (s, 9H); ESMS m/e : 275.2 (M + H) +. Anal. Calc. for [C16H24N202] : C, 70.04 ; H, 8. [08 ;] N, 10. [21.] Found: C, 69.78 ; H, 7.80 ; N, 9.92.
81% With sodium carbonate In 1,2-dimethoxyethane; water for 3 h; Heating / reflux A degassed mixture of 2.0 M aqueous Na2CO3 solution (4.20 mL), tert-butyl 4-[(trifluoromethyl) sulfonyl]oxy}-3,6-dihydro-1 (2H)-pyridine carboxylate (0.500 g, 1.51 mmol), 3-aminophenylboronic acid hemisulfate (0.393 g, 2.11 mmol), lithium chloride (0.191 g, 4.50 mmol) and tetrakis-triphenylphosphine palladium (0.080 g, 0.075 mmol) in dimethoxyethane (5.00 mL) was heated at reflux temperature for 3 hours under Argon. The organic layer of the cooled reaction mixture was separated and the aqueous layer was washed with ethyl acetate (3?50 mL). The combined organic solutions were dried and concentrated in vacuo. The crude product was chromatographed (silica, hexanes:EtOAc: dichloromethane 6:1:1 with 1percent isopropylamine) to give the desired product (0.330 g, 81percent). 1H NMR (400 MHz, CDCl3) ? 7.12 (t, 1H, J=7.60 Hz), 6.78 (d, 1H, J=8.4 Hz), 6.69 (t, 1H, J=2.0 Hz), 6.59 (dd, 1H, J=2.2, 8.0 Hz), 6.01 (br, 1H), 4.10-4.01 (d, 2H, J=2.4 Hz), 3.61 (t, 2H, J=5.6 Hz), 2.52-2.46 (m, 2H), 1.49 (s, 9H); ESMS m/e: 275.2 (M+H)+. Anal. Calc. for C16H24N2O2: C, 70.04; H, 8.08; N, 10.21. Found: C, 69.78; H, 7.80; N, 9.92.
81% With sodium carbonate; lithium chloride In 1,2-dimethoxyethane; water for 3 h; Heating / reflux TERT-BUTYL 4-(3-AMINOPHENYL)-3,6-DIHYDRO-1(2H)-PYRIDINE CARBOXYLATE:
A degassed mixture of 2.0 M aqueous Na2CO3 solution (4.20 mL), tert-butyl 4-[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydro-1(2H)-pyridine carboxylate (0.500 g, 1.51 mmol), 3-aminophenylboronic acid hemisulfate (0.393 g, 2.11 mmol), lithium chloride (0.191 g, 4.50 mmol) and tetrakis-triphenylphosphine palladium (0.080 g, 0.075 mmol) in dimethoxyethane (5.00 mL) was heated at reflux temperature for 3 hours under Argon.
The organic layer of the cooled reaction mixture was separated and the aqueous layer was washed with ethyl acetate (3*50 mL).
The combined organic solutions were dried and concentrated in vacuo.
The crude product was chromatographed (silica, hexanes:EtOAc:dichloromethane 6:1:1 with 1percent isopropylamine) to give the desired product (0.330 g, 81percent).
1H NMR (400 MHz, CDCl3) δ 7.12 (t, 1H, J=7.60 Hz), 6.78 (d, 1H, J=8.4 Hz), 6.69 (t, 1H, J=2.0 Hz), 6.59 (dd, 1H, J=2.2, 8.0 Hz), 6.01 (br, 1H), 4.10-4.01 (d, 2H, J=2.4 Hz) 3.61 (t, 2H, J=5.6 Hz), 2.52-2.46 (m, 2H), 1.49 (s, 9H); ESMS m/e: 275.2 (M+H)+. Anal. Calc. for C16H24N2O2: C, 70.04; H, 8.08; N, 10.21. Found: C, 69.78; H, 7.80; N, 9.92.
Reference: [1] Patent: WO2004/5257, 2004, A1, . Location in patent: Page 53
[2] Patent: US2005/154020, 2005, A1, . Location in patent: Page/Page column 8
[3] Patent: US2005/154022, 2005, A1, . Location in patent: Page/Page column 4; 8-9
  • 2
  • [ 138647-49-1 ]
  • [ 387827-18-1 ]
YieldReaction ConditionsOperation in experiment
60% With sodium carbonate; lithium chloride In 1,2-dimethoxyethane; water at 100℃; A mixture of 2 M AQ NA2C03 solution (42 mL), triflate from Step 1 (50.0 g, 15.1 mmol), 3- aminophenylboronic acid hemisulfate (3.93 g, 2.11 MMOL), lithium chloride (1.91 g, 45.0 mmol), and tetrakis-triphenyl phosphine palladium (0.80 g, 0.75 mmol) in dimethoxyethane (50 mL) was purged with argon and heated at 100°C under an inert atmosphere overnight. The organic layer of the cooled reaction mixture was separated, and the aqueous layer was washed with EtOAc (3x). The combined organic extracts were dried and concentrated in vacuo. The crude product was separated by flash chromatography (silica, EtOAc: Hexane 3: 7) to give the product as a yellow oil (2.5 g, 60 percent). 1H NMR (CDC13) 6 7.25 (s, 1 H), 7.22 (m, 1H), 6.92 (m, 2 H), 6.84 (m, 1H), 6.02 (s, 1H), 4.1 (m, 2H), 3.62 (2 H), 2.49 (s, 2H), 1.49 (s, 9H), 1.26 (t, 2H).
Reference: [1] Patent: WO2004/58727, 2004, A1, . Location in patent: Page 52-53
  • 3
  • [ 138647-49-1 ]
  • [ 387827-18-1 ]
YieldReaction ConditionsOperation in experiment
81% With sodium carbonate; lithium chloride In 1,2-dimethoxyethane; water for 3 h; Heating / reflux A mixture of 2 M aqueous Na2CO3 solution (4.2 mL), tert-butyl 4-[(trifluoromethyl)sulfonyl]oxy}-1,2,3,6-tetrahydro-1-pyridine-carboxylate (0.500 g, 1.51 mmol), 3-aminophenylboronic acid hemisulfate (0.393 g, 2.11 mmol), lithium chloride (0.191 g, 4.50 mmol) and tetrakis-triphenylphosphine palladium(0) (0.080 g, 0.075 mmol) in dimethoxyethane (5 mL) was heated at reflux temperature for 3 hours, under an inert atmosphere (an initial degassing of the mixture is recommended to prevent the formation of triphenylphosphine oxide). The organic layer of the cooled reaction mixture was separated and the aqueous layer was washed with ethyl acetate (3.x.). The combined organic extracts were dried and concentrated in vacuo. The crude product was chromatographed (silica, hexanes:EtOAc:dichloromethane (6:1:1) with 1percent added isopropylamine to protect the BOC group from hydrolysis) to give 0.330 g of the desired product in 81percent yield. 1H NMR (400 MHz, CDCl3) δ 7.12 (t, 1H, J=7.60 Hz), 6.78 (d, 1H, J=8.4 Hz), 6.69 (t, 1H, J=2.0 Hz), 6.59 (dd, 1H, J=2.2, 8.0 Hz), 6.01 (m, 1H), 4.10-4.01 (d, 2H, J=2.4 Hz), 3.61 (t, 2H, J=5.6 Hz), 2.52-2.46 (m, 2H), 1.49 (s, 9H); ESMS m/e: 275.2 (M+H)+. Anal. Calc. for C16H24N2O2: C, 70.04; H, 8.08; N, 10.21. Found: C, 69.78; H, 7.80; N, 9.92.
Reference: [1] Patent: US6727264, 2004, B1, . Location in patent: Page column 56; 91
  • 4
  • [ 79099-07-3 ]
  • [ 387827-18-1 ]
Reference: [1] Molecules, 2013, vol. 18, # 10, p. 12119 - 12143
  • 5
  • [ 159503-90-9 ]
  • [ 387827-18-1 ]
Reference: [1] Molecules, 2013, vol. 18, # 10, p. 12119 - 12143
  • 6
  • [ 30418-59-8 ]
  • [ 138647-49-1 ]
  • [ 387827-18-1 ]
Reference: [1] Molecules, 2013, vol. 18, # 10, p. 12119 - 12143
  • 7
  • [ 387827-18-1 ]
  • [ 387827-19-2 ]
YieldReaction ConditionsOperation in experiment
84% With hydrogen In ethanol at 20℃; for 48 h; A mixture of tert-butyl [4- (3-AMINOPHENYL)-3,] 6-dihydro- [1] [(2H)-PYRIDINECARBOXYLATE] (3.10 g, 11.3 mmol) and 10percent Pd/C (1.00 g) in ethanol (100 [ML)] was hydrogenated at room temperature using the balloon method for 2 days. The reaction mixture was filtered through Celite and washed with ethanol. The combined ethanol extracts were concentrated in vacuo and the residue was chromatographed on silica (dichloromethane: methanol: isopropylamine 95: 5: 1) to give the desired product (2.63 g, [84percent). 1H] NMR (400 MHz, [CDC13)] [8] 7.10 (t, 1H, J = 7.6 [HZ),] 6.62 (d, 1H, J [=] 8.4 Hz), 6.60-6. 59 (m, 2H), 4.27-4. 18 (m, 2H), 3.62-3. 58 (m, 2H), 2.80-2. 72 (m, 2H), 2.62-2. 59 (m, 1H), 1.89-1. 52 (m, 4H), 1.49 (s, 9H); ESMS m/e: [277.] 2 (M + H) [+.]
84% With hydrogen In ethanol at 20℃; for 48 h; A mixture of 3.10 g of tert-butyl 4-(3-aminophenyl)-1,2,3,6-tetrahydropyridine-1-carboxylate (11.3 mmol) and 1.0 g of 10percent Pd/C in 200 mL of ethanol was hydrogenated at room temperature using the balloon method for 2 days. The reaction mixture was filtered and washed with ethanol. The combined ethanol extracts were concentrated in vacuo and the residue was chromatographed on silica (dichloromethane:methanol 95:5 with 1percent isopropylamine added to protect the BOC group from hydrolysis) to give 2.63 g of the desired product (84percent). 1H NMR (400 MHz, CDCl3) δ 7.10 (t, 1H, J=7.60 Hz), 6.62 (d, 1H, J=8.4 Hz), 6.60-6.59 (m, 2H), 4.27-4.18 (m, 2H), 3.62-3.58 (m, 2H), 2.80-2.72 (m, 2H), 2.62-2.59 (m, 1H), 1.89-1.52 (m, 4H), 1.49 (s, 9H); ESMS m/e: 277.2 (M+H)+.
84% With hydrogen In ethanol at 20℃; for 48 h; A mixture of tert-butyl 4-(3-aminophenyl)-3,6-dihydro-1(2H)-pyridinecarboxylate (3.10 g, 11.3 mmol) and 10percent Pd/C (1.00 g) in ethanol (100 mL) was hydrogenated at room temperature using the balloon method for 2 days. The reaction mixture was filtered through Celite and washed with ethanol. The combined ethanol extracts were concentrated in vacuo and the residue was chromatographed on silica (dichloromethane:methanol:isopropylamine 95:5:1) to give the desired product (2.63 g, 84percent). 1H NMR (400 MHz, CDCl3) ? 7.10 (t, 1H, J=7.6 Hz), 6.62 (d, 1H, J=8.4 Hz), 6.60-6.59 (m, 2H), 4.27-4.18 (m, 2H), 3.62-3.58 (m, 2H), 2.80-2.72 (m, 2H), 2.62-2.59 (m, 1H), 1.89-1.52 (m, 4H), 1.49 (s, 9H); ESMS m/e: 277.2 (M+H)+.
84% With hydrogen In ethanol at 20℃; for 48 h; TERT-BUTYL 4-[3-(AMINO)PHENYL]-1-PIPERIDINECARBOXYLATE:
A mixture of tert-butyl 4-(3-aminophenyl)-3,6-dihydro-1(2H)-pyridinecarboxylate (3.10 g, 11.3 mmol) and 10percent Pd/C (1.00 g) in ethanol (100 mL) was hydrogenated at room temperature using the balloon method for 2 days.
The reaction mixture was filtered through Celite and washed with ethanol.
The combined ethanol extracts were concentrated in vacuo and the residue was chromatographed on silica (dichloromethane:
methanol:isopropylamine 95:5:1) to give the desired product (2.63 g, 84percent).
1H NMR (400 MHz, CDCl3) δ 7.10 (t, 1H, J=7.6 Hz), 6.62 (d, 1H, J=8.4 Hz), 6.60-6.59 (m, 2H), 4.27-4.18 (m, 2H), 3.62-3.58 (m, 2H), 2.80-2.72 (m, 2H), 2.62-2.59 (m, 1H), 1.89-1.52 (m, 4H), 1.49 (s, 9H); ESMS m/e: 277.2 (M+H)+.
63% With hydrogen In ethanol at 20℃; for 48 h; A mixture OF TERT-BUTYL 4- (3-AMINOPHENYL)-3, 6-DIHYDRO-1 (2H) -pyridinecarboxylate (3.30 g, 12.03 mmol) and 1.0 g of 10percent Pd/C in 200 mL ethanol was hydrogenated at rt for 2 days. The reaction mixture was filtered and washed with ethanol. The combined ethanol extracts were concentrated in vacuo to afford the desired product (2.1 g, 63percent). LC-MS M+H 276.7, RT 2. 0.5 1H NMR (DMSO): 6 6.9 (s, 1H), 6.4 (m, 3H), 4.9 (s, 2H), 4.0 (m, 2H), 2.7 (m, 2H), 1.7 (d, 2H), 1.4 (s, 9H).

Reference: [1] Patent: US2004/38855, 2004, A1,
[2] Patent: WO2004/5257, 2004, A1, . Location in patent: Page 54
[3] Patent: US6727264, 2004, B1, . Location in patent: Page column 56; 91
[4] Patent: US2005/154020, 2005, A1, . Location in patent: Page/Page column 8
[5] Patent: US2005/154022, 2005, A1, . Location in patent: Page/Page column 4; 9
[6] Patent: WO2004/58727, 2004, A1, . Location in patent: Page 52-53
  • 8
  • [ 387827-18-1 ]
  • [ 75-31-0 ]
  • [ 387827-19-2 ]
Reference: [1] Patent: US2003/69261, 2003, A1,
[2] Patent: US2003/82623, 2003, A1,
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