[ CAS No. 1233339-22-4 ] {[proInfo.proName]}

Name: 1233339-22-4|(R)-4-(2-(1H-Indol-4-yl)-6-(1-(methylsulfonyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine|98%
Brand: Ambeed
SKU: A838709
Price: 35.0 USD
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2D 3D

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Quality Control of [ 1233339-22-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1233339-22-4 ]

SDS Specification

Alternatived Products of [ 1233339-22-4 ]

Product Details of [ 1233339-22-4 ]

CAS No. :	1233339-22-4	MDL No. :	MFCD25976730
Formula :	C₂₁H₂₄N₄O₃S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SCGCBAAYLFTIJU-CQSZACIVSA-N
M.W :	412.51	Pubchem ID :	46244454
Synonyms :

Calculated chemistry of [ 1233339-22-4 ]

Physicochemical Properties

Num. heavy atoms :	29
Num. arom. heavy atoms :	15
Fraction Csp3 :	0.43
Num. rotatable bonds :	4
Num. H-bond acceptors :	5.0
Num. H-bond donors :	1.0
Molar Refractivity :	115.98
TPSA :	96.56 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-7.35 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.79
Log Po/w (XLOGP3) :	2.06
Log Po/w (WLOGP) :	3.41
Log Po/w (MLOGP) :	1.64
Log Po/w (SILICOS-IT) :	3.17
Consensus Log Po/w :	2.61

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.81
Solubility :	0.0633 mg/ml ; 0.000153 mol/l
Class :	Soluble
Log S (Ali) :	-3.72
Solubility :	0.0792 mg/ml ; 0.000192 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-6.44
Solubility :	0.00015 mg/ml ; 0.000000363 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	4.03

Safety of [ 1233339-22-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1233339-22-4 ]

* 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 [ 1233339-22-4 ]

[ 1233339-22-4 ] Synthesis Path-Upstream 1~10

1
[ 1233339-68-8 ]
[ 220465-43-0 ]
[ 1233339-22-4 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium carbonate In 1,2-dimethoxyethane; water at 90℃;	Example 3.014-{4-r(3R)-3-Methylmorpholin-4-yl1-6-ri-(methylsulfonyl)cvclopropyl1pyrimidin-2-yl}- lH-indoleBis(triphenylphosphine)palladium chloride (1.692 g, 2.41 mmol), (R)-4-(2-chloro-6-(l- (methylsulfonyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (8.00 g, 24.11 mmol), IH- indol-4-ylboronic acid (4.27 g, 26.52 mmol) and 2M aqueous sodium carbonate (36.2 rnL, 72.33 mmol) were suspended in DME:water 4:1 (170 mL) and heated to 90 ⁰C overnight. The DME was removed and the reaction mixture diluted with EtOAc (100 mL). The mixture was washed with water (2 x 100 mL), the organics separated, filtered through a pad of Celite and concentrated in vacuo on to silica. The residue was purified by chromatography on silica with an elution gradient of 0 to 10percent EtOAc in DCM. Fractions containing product were combined and evaporated. The residue was purified by chromatography on silica eluting with a gradient of 0-25percent EtOAc in DCM. Fractions containing product were combined and evaporated onto reverse phase Cl 8 silica. The crude product was purified by reverse phase using a 415g HP Cl 8 column using decreasingly polar mixtures of water (containing 1percent NH3) and MeCN as eluents. Fractions containing product were combined and evaporated. The residue was taken up in dry MeOH and dried over MgSO4. The mixture was filtered and the solvent evaporated, leaving a gum. The gum was dissolved in DCM (500 mL), filtered and the solvent removed under reduced pressure. The residue was dissolved in MeOH (50 mL) and allowed to stir at RT overnight. The resultant precipitate was collected by filtration to afford the title compound (5.1O g, 51percent); ¹H NMR (400 MHz, DMSO-/): 1.29 (3H, d), 1.57 - 1.64 (2H, m), 1.68 - 1.78 (2H, m), 3.24-3.31 (IH, td), 3.29 (3H, s), 3.51 (IH, td), 3.67 (IH, dd), 3.80 (IH, d), 3.93 - 4.06 (IH, dd), 4.21 (IH, d), 4.61 (IH, bs), 6.85 (IH, s), 7.21 (IH, t), 7.32 (IH, t), 7.46 (IH, t), 7.56 (IH, d), 8.06 (IH, dd), 11.25 (IH, s); m/z: (ESI+) MH⁺, 413.12. Chiral HPLC: (HPI lOO System 4, 5μm Chiralpak AS-H (250mm x 4.6mm) column eluting with iso- Hexane/EtOH/TEA 60/40/0.1) Rf, 8.815 >99percent.

Reference： [1] Patent: WO2010/73034, 2010, A1, . Location in patent: Page/Page column 68-69
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 5, p. 2125 - 2138

2
[ 1233339-68-8 ]
[ 1233339-22-4 ]

Yield	Reaction Conditions	Operation in experiment
64%	With potassium phosphate; (2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1’-biphenyl)[2-(2’-amino-1,1’-biphenyl)]palladium(II) methanesulfonate In 1,2-dimethoxyethane; water at 70℃; for 20 h; Inert atmosphere	A mixture of (3R)-4-[2-chloro-6-(1-methanesulfonylcyclopropyl)pyrimidin-4-yl]-3-methylmorpholine 19(0.672 g, 2.02 mmol), (1H-indo-4-yl)boronic acid, 20 (1.14 g, 7.09 mmol), 1.2 M aqueous solution ofpotassium phosphate (6.08 mmol), and 1,2-dimethoxyethane (15 mL) in 25 mL pressure flask wasdeoxygenated by passing a slow stream of nitrogen (about 50 mL/min) for 20 min. Then, XPhos PdG3 (0.10 g, 0.12 mol) was added in one portion. The flask was closed and the mixture was heated at70 °C with stirring for 20 h. The reaction mixture was diluted with 50 mL of EtOAc. The mixture waswashed with water (1x50 mL). The organics were separated; the aqueous solution was extracted withethyl acetate (3x50 mL). Combined organics were dried over magnesium sulfate, filtered andconcentrated in vacuo to afford crude product (about 1.0 g) as brown oil. The crude was purified onsilica (Biotage system, 40 g cartridge) with 0-30percent gradient of EtOAc/EtOH (4:1) in hexanes. Fractionscontaining product were combined, evaporated, and dried under vacuum to afford 21 as white solid(0.531 g, 64percent ). 1H NMR (400 MHz, DMSO-d6) δ 1.26 (d, J = 6.7 Hz, 3H), 1.60 (td, J = 5.7, 5.0, 3.5Hz, 2H), 1.71 (qd, J = 4.1, 3.4, 1.3 Hz, 2H), 3.22 (d, J = 3.9 Hz, 1H), 3.28 (s, 3H), 3.50 (td, J = 11.8,3.0 Hz, 1H), 3.65 (dd, J = 11.5, 3.2 Hz, 1H), 3.78 (d, J = 11.4 Hz, 1H), 3.99 (dd, J = 11.4, 3.6 Hz, 1H),4.20 (d, J = 13.5 Hz, 1H), 4.60 (s, 1H), 6.83 (s, 1H), 7.20 (t, J = 7.7 Hz, 1H), 7.31 (t, J = 2.6 Hz, 1H),7.46 (t, J = 2.8 Hz, 1H), 7.54 (dd, J = 8.0, 1.0 Hz, 1H), 8.05 (dd, J = 7.5, 1.0 Hz, 1H), 11.28 (t, J = 2.3Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ 12.78, 13.87, 39.34, 40.81, 46.62, 46.87, 66.54, 70.71,101.01, 103.33, 114.29, 120.92, 121.06, 126.75, 126.80, 129.84, 137.48, 161.99, 162.45, 164.94.MS-ESI m/z 413.26 [MH]+. Anal. Found (percent w/w): C, 61.27; H, 6.02; N, 13.42. C21H24N4O3S requiresC, 61.15; H, 5.86; N, 13.58. [α]23D -88.3 (c 1.03, DMSO).

Reference： [1] Chem, 2018, vol. 4, # 3, p. 522 - 532

3
[ 1233339-73-5 ]
[ 1233339-22-4 ]

Reference： [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 5, p. 2125 - 2138
[2] Chem, 2018, vol. 4, # 3, p. 522 - 532

4
[ 1233339-71-3 ]
[ 1233339-22-4 ]