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[ CAS No. 883984-95-0 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 883984-95-0
Chemical Structure| 883984-95-0
Chemical Structure| 883984-95-0
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Product Details of [ 883984-95-0 ]

CAS No. :883984-95-0 MDL No. :MFCD19703288
Formula : C19H18ClN3O4 Boiling Point : -
Linear Structure Formula :- InChI Key :BTFWVGMXDFRSMY-UHFFFAOYSA-N
M.W : 387.82 Pubchem ID :59165781
Synonyms :

Calculated chemistry of [ 883984-95-0 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 27
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.32
Num. rotatable bonds : 4
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 105.6
TPSA : 80.76 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.51 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.11
Log Po/w (XLOGP3) : 3.04
Log Po/w (WLOGP) : 2.71
Log Po/w (MLOGP) : 2.11
Log Po/w (SILICOS-IT) : 2.5
Consensus Log Po/w : 2.69

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.22
Solubility : 0.0231 mg/ml ; 0.0000596 mol/l
Class : Moderately soluble
Log S (Ali) : -4.4
Solubility : 0.0154 mg/ml ; 0.0000396 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -5.85
Solubility : 0.000548 mg/ml ; 0.00000141 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 4.17

Safety of [ 883984-95-0 ]

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 [ 883984-95-0 ]

* 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 [ 883984-95-0 ]
  • Downstream synthetic route of [ 883984-95-0 ]

[ 883984-95-0 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 883984-95-0 ]
  • [ 753440-87-8 ]
Reference: [1] Patent: WO2007/16087, 2007, A2, . Location in patent: Page/Page column 49; 66
[2] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 22, p. 6368 - 6372
[3] Patent: WO2006/41830, 2006, A2, . Location in patent: Page/Page column 55
[4] Patent: WO2006/44504, 2006, A1, . Location in patent: Page/Page column 80
[5] Patent: WO2006/99268, 2006, A2, . Location in patent: Page/Page column 66
  • 2
  • [ 19099-93-5 ]
  • [ 159603-71-1 ]
  • [ 883984-95-0 ]
YieldReaction ConditionsOperation in experiment
54%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -78℃; for 2.83333 h; Inert atmosphere
Stage #2: at -78 - 40℃; Inert atmosphere
Stage #3: With water; sodium hydrogencarbonate In tetrahydrofuran
Step 2:
benzyl 7'-chloro-2'-oxo-1',2'-dihydrospiro[piperidine-4,4'-pyrido[2,3d][1,3]-oxazin]-1-carboxylate
Under a nitrogen atmosphere 26 mL (1734 mmol) N,N,N,N-tetramethylenethylenediamine in 180 mL THF were cooled to -20° C. and 70 mL (175 mmol) of a 2.5 molar butyllithium solution were added within 10 min.
After 30 minutes' stirring the reaction mixture was cooled to -78° C. and at this temperature 17.8 g (78.0 mmol) tert-butyl (6-chloro-pyridin-2-yl)-carbamate in 120 mL THF were added dropwise within 20 min.
The reaction mixture was stirred for 2.5 h at -78° C. and then 27.2 g (116.7 mmol) benzyl 4-oxo-piperidine-1-carboxylate in 60 mL THF were added within 10 min.
After another hour's stirring at -78° C. the reaction mixture was first of all heated to RT and then stirred for 18 h at 40° C.
Then the reaction mixture was decomposed by the dropwise addition of 150 mL saturated sodium hydrogen carbonate solution.
Then the reaction mixture was extracted several times with DCM.
The combined organic phases were washed with water, dried and evaporated down.
The residue was triturated with PE/EtOAc 1/1, the precipitate formed was suction filtered, washed with PE/ETOAc 1/1 and dried.
Yield: 16.4 g (54percent of theoretical)
ESI-MS: m/z=388 (M+H)+
Rt(HPLC): 1.57 min (method C)
54%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -78℃; for 2.5 h; Inert atmosphere
Stage #2: at -78 - 40℃; for 19 h;
Step 2: benzyl-7'-chloro-2'-oxo-1',2'-dihydrospiro[piperidin-4,4'-pyrido[2,3d][1,3]oxazin]-1-carboxylate; Under a nitrogen atmosphere 26.0 mL (173 mmol) N,N,N,N-tetramethylene-ethylenediamine in 180 mL THF were cooled to -20° C. and combined with 70.0 mL (175 mmol) 2.5 M butyllithium solution. After 30 minutes' stirring the reaction mixture was cooled to -78° C., and at this temperature 17.8 g (78.0 mmol) tert-butyl (6-chloro-pyridin-2-yl)-carbamate in 120 mL THF were slowly added dropwise. The reaction mixture was stirred for 2.5 h at -78° C. and then combined with 27.2 g (117 mmol) Cbz-protected piperidone in 60 mL of THF. After one hour at -78° C. the mixture was heated to RT and then stirred for 18 h at 40° C. The reaction mixture was decomposed by the dropwise addition of 150 mL saturated sodium hydrogen carbonate solution. Then it was extracted with DCM. The combined organic phases were washed with water, dried and evaporated down. The residue was triturated with PE/EtOAc (1/1), the precipitate formed was suction filtered, washed with PE/EtOAc (1/1) and dried.Yield: 16.4 g (54percent of theoretical)ESI-MS: m/z=388 (M+H)+ Rt(HPLC): 1.57 min (method B)
54% With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -78 - 40℃; Inert atmosphere Step 2: benzyl 7'-chloro-2'-oxo-1',2'-dihydrospiro[piperidine-4,4'-pyrido[2,3d]-[1,3]oxazine]-1-carboxylate Under a nitrogen atmosphere 26 mL (173.39 mmol) N,N,N,N-tetramethylenethylene-diamine in 180 mL THF were cooled to -20° C. and within 10 min 70 mL (175 mmol) of a 2.5 molar butyllithium solution were added. After 30 minutes' stirring the reaction mixture was cooled to -78° C. and at this temperature 17.84 g (78.00 mmol) tert-butyl (6-chloro-pyridin-2-yl)-carbamate in 120 mL THF were added dropwise within 20 min. The reaction mixture was stirred for 2.5 h at -78° C. and then combined with 27.22 g (116.70 mmol) Z-piperidone in 60 mL THF within 10 min. After a further hour's stirring at -78° C. the reaction mixture was first of all heated to RT and then stirred for 18 h at 40° C. Then the reaction mixture was decomposed by the dropwise addition of 150 mL saturated sodium hydrogen carbonate solution. Then the reaction mixture was extracted several times extracted with DCM. The combined organic phases were washed with water, dried and evaporated down. The residue was triturated with PE/EtOAc 1/1, the precipitate formed was suction filtered, washed with PE/ETOAc 1/1 and dried.Yield: 16.40 g (54percent of theoretical)ESI-MS: m/z=388 (M+H)+ Rt(HPLC): 1.57 min (method C)
Reference: [1] Patent: US2011/21500, 2011, A1, . Location in patent: Page/Page column 45-46
[2] Patent: US2011/172218, 2011, A1, . Location in patent: Page/Page column 29-30
[3] Patent: US2012/149698, 2012, A1, . Location in patent: Page/Page column 26
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 22, p. 6368 - 6372
[5] Patent: WO2006/41830, 2006, A2, . Location in patent: Page/Page column 55
[6] Patent: WO2006/44504, 2006, A1, . Location in patent: Page/Page column 79
[7] Patent: WO2006/99268, 2006, A2, . Location in patent: Page/Page column 65-66
[8] Patent: US2018/50992, 2018, A1, . Location in patent: Paragraph 1392
  • 3
  • [ 19099-93-5 ]
  • [ 883984-95-0 ]
Reference: [1] Patent: WO2007/16087, 2007, A2, . Location in patent: Page/Page column 49; 66
  • 4
  • [ 45644-21-1 ]
  • [ 883984-95-0 ]
Reference: [1] Patent: US2011/172218, 2011, A1,
[2] Patent: US2012/149698, 2012, A1,
[3] Patent: US2018/50992, 2018, A1,
  • 5
  • [ 883984-95-0 ]
  • [ 1038866-44-2 ]
YieldReaction ConditionsOperation in experiment
50% With hydrogen In ethanol at 20℃; for 9 h; Step 3:
spiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride
16.4 g (42.4 mmol) benzyl 7'-chloro-2'-oxo-1'.2'-dihydrospiro[piperidine-4,4'-pyrido[2,3d][1,3]oxazine]-1-carboxylate and 2.00 g palladium(Pd/C 10percent) in 500 mL EtOH were hydrogenated in a hydrogen atmosphere for 6 h at RT.
Then another 1.0 g palladium (Pd/C 10percent) were added the mixture was hydrogenated for a further 3 h at RT in a hydrogen atmosphere.
After filtration of the reaction mixture the solvent was eliminated in vacuo.
The residue was triturated with EtOH, the precipitate formed was suction filtered, washed with EtOH and dried.
Yield: 5.40 g (50percent of theoretical)
ESI-MS: m/z=220 (M+H)+
Rt(HPLC): 0.90 min (method C)
50% With hydrogen In ethanol at 20℃; for 9 h; Step 3: spiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride 16.40 g (0.04 mol) benzyl 7'-chloro-2'-oxo-1',2'-dihydrospiro[piperidine-4,4'-pyrido[2,3d]-[1,3]oxazine]-1-carboxylate and 2.00 g palladium(Pd/C 10percent) in 500 mL EtOH were hydrogenated for 6 h at RT in a hydrogen atmosphere. Then 1 g of palladium (Pd/C 10percent) were additionally added and the mixture was hydrogenated for a further 3 h at RT in a hydrogen atmosphere. After filtration of the reaction mixture the solvent was eliminated in vacuo. The residue was triturated with EtOH, the precipitate formed was suction filtered, washed with EtOH and dried in the drying cupboard for 3 h at 50° C.Yield: 5.40 g (50percent of theoretical)ESI-MS: m/z=220 (M+H)+ Rt(HPLC): 0.90 min (method C)
Reference: [1] Patent: US2011/21500, 2011, A1, . Location in patent: Page/Page column 46
[2] Patent: US2012/149698, 2012, A1, . Location in patent: Page/Page column 26
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