Home Cart 0 Sign in  

[ CAS No. 1234356-69-4 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 1234356-69-4
Chemical Structure| 1234356-69-4
Structure of 1234356-69-4 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1234356-69-4 ]

Related Doc. of [ 1234356-69-4 ]

Alternatived Products of [ 1234356-69-4 ]

Product Details of [ 1234356-69-4 ]

CAS No. :1234356-69-4 MDL No. :MFCD30532770
Formula : C29H29FN4O Boiling Point : -
Linear Structure Formula :- InChI Key :KPJDVVCDVBFRMU-AREMUKBSSA-N
M.W : 468.57 Pubchem ID :46834118
Synonyms :
ARQ-087

Calculated chemistry of [ 1234356-69-4 ]

Physicochemical Properties

Num. heavy atoms : 35
Num. arom. heavy atoms : 24
Fraction Csp3 : 0.24
Num. rotatable bonds : 9
Num. H-bond acceptors : 5.0
Num. H-bond donors : 2.0
Molar Refractivity : 137.36
TPSA : 59.07 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -5.42 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.98
Log Po/w (XLOGP3) : 5.27
Log Po/w (WLOGP) : 5.91
Log Po/w (MLOGP) : 4.04
Log Po/w (SILICOS-IT) : 6.19
Consensus Log Po/w : 5.08

Druglikeness

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

Water Solubility

Log S (ESOL) : -5.98
Solubility : 0.000492 mg/ml ; 0.00000105 mol/l
Class : Moderately soluble
Log S (Ali) : -6.26
Solubility : 0.000257 mg/ml ; 0.000000549 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -11.51
Solubility : 0.0000000014 mg/ml ; 0.0 mol/l
Class : Insoluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 3.0
Synthetic accessibility : 4.36

Safety of [ 1234356-69-4 ]

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 [ 1234356-69-4 ]

* 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 [ 1234356-69-4 ]
  • Downstream synthetic route of [ 1234356-69-4 ]

[ 1234356-69-4 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 124-63-0 ]
  • [ 109-85-3 ]
  • [ 1234356-69-4 ]
YieldReaction ConditionsOperation in experiment
86%
Stage #1: With sodium hydroxide In 2-methyltetrahydrofuran at 20 - 25℃; for 1 h; Large scale
Stage #2: With triethylamine In 2-methyltetrahydrofuran at 0 - 25℃; for 6 h; Large scale
Stage #3: at 50 - 55℃; for 13 h; Large scale
Starting material: Compound 4 Methanesulfonyl chloride (MsCl) [CAS 124-63-0] 2-Methoxyethylamine [CAS 109-85-3] Reagents: Sodium Chloride (NaCl) 50percent Sodium Hydroxide (NaOH) Triethylamine (Et3N) (0258) Solvents: n-Heptane Isopropyl Acetate (zPrOAc) 2-Methyl Tetrahydrofuran (2-MeTHF) A 100-gallon reactor was charged with Compound 4 (10.4 kg, 23.2 mol, 1.0 eq) and 2- methyltetrahydrofuran (2-MeTHF, 132.6 kg, 155.2 L, 15 vol). A solution of 1.0 M NaOH (48.5 L, 48.5 mol, 2.1 eq) was added in one portion to the slurry and the resulting biphasic mixture was allowed to stir at 20-25 °C for 1.0 h. The phases were allowed to settle, the lower aqueous layer was removed and the organic layer was washed with 2.5percent NaCl (52 L, 5 vol). The organic layer was concentrated down to 104 L (10 vol) and chased with 2-MeTHF (44.0 kg, 51.5 L, 5 vol) a total of five times to achieve the desired water content of <0.1percent (0.08percent). After pohsh-filtering the 2-MeTHF solution into a clean 100-gallon reactor, triethylamine (Et3N, 3.5 kg, 4.9 L, 34.8 mol, 1.5 eq) was added and the mixture was cooled to 0-5 °C. Methanesulfonyl chloride (MsCL 4.0 kg, 2.7 L, 34.8 mol, 1.5 eq) was added over a period of 1 h while keeping the internal temperature < 20 °C. Once the addition of MsCl was complete, the reaction temperature was adjusted to 20-25 ''C and the mixture was stirred for 2 h. Analysis by HPLC indicated the presence of 3.7percent Compound 4. Additional Et3N (0.4 kg, mL, 0.55 L, 4.0 mol, 0.2 eq) and MsCl (0.4 kg, 0.27 L, 3.5 mol, 0.15 eq) were charged and the mixture was stirred at 20-25 °C for 1.5 h. At this point, 0.57percent Compound 4 was detected by HPLC. Additional Et3N (0.1 kg, mL, 0.14 L, 1.0 mol, 0.05 eq) and MsCl (0.1 kg, 0.07 L, 1.0 mol, 0.05 eq) were charged and the mixture was stirred at 20-25 °C for 1.5 h. Water (93.5 kg, 9 vol) was added and the biphasic mixture was stirred for 2.5 h. The phases were allowed to settle for 1 h and the aqueous layer was then transferred to a clean 200-gallon reactor. The aqueous layer was back-extracted with 2-MeTHF (44.6 kg, 52.2 L, 5 vol) and the upper layer was transferred to the 100-gallon reactor to combine organic layers before being washed with 5percent NaCl (51.6 kg, 5 vol). The resulting 2-MeTHF solution was concentrated down to -104 L (10 vol) and then chased with 2-MeTHF (44.0 kg, 51.5 L, 5 vol) a total of five times to achieve the desired water content of <0.1percent (0.02percent). After polish-filtering the 2-MeTHF solution into a clean 100-gallon reactor, the solution containing Compound 5 was concentrated down to 52 L (5 vol). 2-methoxyethylamine (35.8 kg, 41.4 L, 4 vol) was added, and the resulting reaction mixture was heated to 50-55 °C. The reaction mixture was allowed to stir at temperature for 13 h and HPLC analysis indicated complete conversion. Once the transformation was deemed complete, isopropylacetate (iPrOAc, 117.8 kg, 135L, 13 vol) and water (104 kg, 10 vol) were charged to the reactor while maintaining a temperature of 50-55 °C. After stirring for 1.5 h, the water layer was transferred to a clean 200-gallon reactor and extracted with iPrOAc (61.8 kg, 70.9 L, 7 vol). The upper layer was transferred to the 100- gallon reactor to combine organic layers and then re-equilibrated at 50-55 °C. The combined organic layer was washed with water (4x20.8 kg, 4x2 vol) before being vacuum distilled down to 63L (6 vol). The resulting slurry was chased with w-heptane (3x85.0 kg, 3x124 L, 3x12 vol) down to ~6 vol to achieve < 8.5 wtpercent of residual iPrOAc (1.1 wtpercent). The slurry was diluted with n-heptane (42.7 kg, 62.4 L, 6 vol) and stirred at 20-25 °C for 16.0 h before being filtered. The filter cake was washed with heptane (2x28.4 kg, 2x41.5 L, 2x4 vol) and then dried at 40-45 °C for 30 h. Compound A was obtained (9.4 kg, 86percent yield, 96.6percent AUC by HPLC) as a cream colored solid. Example 4. Preparation of ARQ 087-2 HC1 Crystalline Form D
Reference: [1] Patent: WO2017/106639, 2017, A1, . Location in patent: Page/Page column 38; 39
  • 2
  • [ 1234356-88-7 ]
  • [ 1234356-69-4 ]
Reference: [1] Patent: WO2017/106639, 2017, A1,
  • 3
  • [ 1282453-21-7 ]
  • [ 1234356-69-4 ]
Reference: [1] Patent: WO2017/106639, 2017, A1,
Same Skeleton Products
Historical Records

Similar Product of
[ 1234356-69-4 ]

Chemical Structure| 1821329-75-2

A388814[ 1821329-75-2 ]

ARQ-087 2HCl

Reason: Free-salt