Home Cart 0 Sign in  

[ CAS No. 841290-80-0 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 841290-80-0
Chemical Structure| 841290-80-0
Structure of 841290-80-0 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 841290-80-0 ]

Related Doc. of [ 841290-80-0 ]

Alternatived Products of [ 841290-80-0 ]

Product Details of [ 841290-80-0 ]

CAS No. :841290-80-0 MDL No. :MFCD09970820
Formula : C22H23FN6O5 Boiling Point : -
Linear Structure Formula :- InChI Key :NHHQJBCNYHBUSI-UHFFFAOYSA-N
M.W : 470.45 Pubchem ID :11213558
Synonyms :
R406;free base

Calculated chemistry of [ 841290-80-0 ]

Physicochemical Properties

Num. heavy atoms : 34
Num. arom. heavy atoms : 18
Fraction Csp3 : 0.27
Num. rotatable bonds : 7
Num. H-bond acceptors : 9.0
Num. H-bond donors : 3.0
Molar Refractivity : 124.82
TPSA : 128.75 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.96 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.3
Log Po/w (XLOGP3) : 3.11
Log Po/w (WLOGP) : 3.48
Log Po/w (MLOGP) : 1.56
Log Po/w (SILICOS-IT) : 2.46
Consensus Log Po/w : 2.78

Druglikeness

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

Water Solubility

Log S (ESOL) : -4.65
Solubility : 0.0106 mg/ml ; 0.0000226 mol/l
Class : Moderately soluble
Log S (Ali) : -5.48
Solubility : 0.00155 mg/ml ; 0.00000329 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -7.93
Solubility : 0.00000553 mg/ml ; 0.0000000117 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.86

Safety of [ 841290-80-0 ]

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 [ 841290-80-0 ]

* 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 [ 841290-80-0 ]
  • Downstream synthetic route of [ 841290-80-0 ]

[ 841290-80-0 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 575484-83-2 ]
  • [ 24313-88-0 ]
  • [ 841290-80-0 ]
YieldReaction ConditionsOperation in experiment
91% at 120℃; for 10 h; Inert atmosphere; Large scale Step B:
Preparation of 6-[[5-Fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one
6-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one (Step A) (568 kg, 1.00 mol eq) is mixed with 3,4,5-trimethoxyaniline (402 kg, 1.25 mol eq) in N-methylpyrrolidin-2-one (2835 kg) with stirring under a nitrogen atmosphere.
To this is added water (11 kg) and the mixture heated to about 120° C. and stirred for about 10 hours.
This is then cooled to about 65° C. and the pH adjusted to pH 8.5 with 4percent w/w aqueous sodium hydroxide solution.
The resulting slurry is further cooled to about 20° C., stirred for at least 6 hours and then filtered.
The filtered solid is washed twice with water (2*1440 kg) then twice with acetone (2*1140 kg) and finally dried under vacuum at about 40° C. to give the title compound (754 kg, 91percent) as a colored solid.
1H NMR (400 MHz, DMSO-d6) δ ppm 1.42 (s, 6H) 3.59 (s, 3H) 3.66 (s, 6H) 7.04 (s, 2H) 7.32 (d, J=8.5 Hz, 1H) 7.68 (d, J=8.5 Hz, 1H) 8.13 (d, J=3.4 Hz, 1H) 9.10 (br. s, 1H) 9.14 (br. s, 1H) 11.06 (br. s, 1H).
m/z 471 [MH]+.
Reference: [1] Patent: US2015/175639, 2015, A1, . Location in patent: Paragraph 0149; 0150; 0151; 0152
  • 2
  • [ 901119-38-8 ]
  • [ 841290-80-0 ]
  • [ 901119-35-5 ]
YieldReaction ConditionsOperation in experiment
52% With trifluoroacetic acid In dichloromethane at 0℃; for 1.58 h; 7.1.2 N4-(2,2-dimethy1-4-[(dihydrogen phosphonoxy)methyl]-3-oxo-5- pyrido[l,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4- pyrimidinediamine (Compound 4); [0210] Trifluoroacetic acid (1.5 mL) was added dropwise as a neat for 5 min to N4-(2,2- dimethy1-4-[(di-tert-butyl phosphonoxy)methyl] -3 -oxo-5-pyrido [ 1 ,4] oxazin-6-yl)-5-fluoro- N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine (Compound 3, 120 mg, 0.173 mmol ) dissolved in CH2Cl2 (10 mL) at O0C under nitrogen atmosphere. The contents were allowed to stir for 1.5 h. Progress of the reaction mixture was monitored by LC/MS. After complete consumption of the starting material, reaction mixture was concentrated, dried and triturated with ether. The ethereal layer was decanted and dried to provide the crude solid. LC/MS analysis of the crude displayed three peaks with M++H 581, 471 and 501. The peak corresponding to M++H 581 was collected by preparative HPLC chromatographic purification. The fractions were lyophilised and dried to provide 53 mg (52percent) of off white fluffy solid and characterized as N4-(2,2-dimethy1-4-[(dihydrogen phosphonoxy)methyl]-3- oxo-5-pyrido[l,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine (Compound 4). 1H NMR (DMSO-d6): δ 9.21 (br s, 2H), 8.16 (d, 1H, J = 2.6 Hz), 7.93 (d, 1H, J = 8.5 Hz), 7.39 (d, 1H, J = 8.5 Hz), 7.05 (s, 2H), 5.79 (d, 1H, J3PH = 6.6 Hz), 3.67 (s, 6H), 3.59 (s, 3H), 1.44 (s, 6H). LCMS: ret. time: 8.52 min.; purity: 95percent; MS (m/e): 581 (MH+). 31P NMR (DMSO-d6): -2.17.
Reference: [1] Patent: WO2006/78846, 2006, A1, . Location in patent: Page/Page column 75-76
Same Skeleton Products
Historical Records