122194-07-4|Dimethyl n,n-diisopropylphosphoramidite| Ambeed

CAS No. :	122194-07-4
Formula :	C₈H₂₀NO₂P
M.W :	193.22
SMILES Code :	CC(N(C(C)C)P(OC)OC)C
MDL No. :	MFCD00153505
InChI Key :	KXUMNSXPAYCKPR-UHFFFAOYSA-N
Pubchem ID :	5171659

Safety of [ 122194-07-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 122194-07-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	0
Fraction Csp3	1.0
Num. rotatable bonds	5
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	53.61
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	35.29 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.9
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.86
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.62
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.22
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.03
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.93

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.88
Solubility	2.55 mg/ml ; 0.0132 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.22
Solubility	1.16 mg/ml ; 0.00599 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.23
Solubility	11.3 mg/ml ; 0.0586 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.16 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	3.42

Application In Synthesis of [ 122194-07-4 ]

* 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.

Downstream synthetic route of [ 122194-07-4 ]

[ 122194-07-4 ] Synthesis Path-Downstream 1~54

1
[ 67-56-1 ]
[ 96163-52-9 ]
[ 122194-07-4 ]

References: [1]Tetrahedron Letters,1990,vol. 31,p. 6363 - 6366.

2
[ 67-56-1 ]
[ 92611-10-4 ]
[ 122194-07-4 ]

References: [1]Journal of the American Chemical Society,1986,vol. 108,p. 2040 - 2048.

3
[ 3120-74-9 ]
[ 122194-07-4 ]
[ 108-18-9 ]
[ 154469-89-3 ]

References: [1]Journal of labelled compounds and radiopharmaceuticals,1994,vol. 34,p. 73 - 78.

4
[ 124-41-4 ]
[ 86030-43-5 ]
[ 122194-07-4 ]

References: [1]Journal of labelled compounds and radiopharmaceuticals,1994,vol. 34,p. 73 - 78.

5
[ 21090-30-2 ]
[ 122194-07-4 ]
[ 116864-28-9 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1994,p. 2123 - 2130.

6
[ 122194-07-4 ]
[ 85231-45-4 ]
4-Oxo-pentanoic acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-(dimethoxy-phosphanyloxymethyl)-tetrahydro-furan-3-yl ester [ No CAS ]

References: [1]Tetrahedron,1994,vol. 50,p. 10225 - 10234.

7
[ 122194-07-4 ]
[ 868-85-9 ]

References: [1]Tetrahedron Letters,1990,vol. 31,p. 6363 - 6366.

8
[ 122194-07-4 ]
[ 51549-40-7 ]
[ 146578-13-4 ]

References: [1]Tetrahedron Letters,1992,vol. 33,p. 7319 - 7323.

9
[ 122194-07-4 ]
[ 5983-14-2 ]
[ 122194-08-5 ]

References: [1]Tetrahedron,1994,vol. 50,p. 10225 - 10234.

10
[ 22147-29-1 ]
[ 122194-07-4 ]
glyceryl dimethyl phosphite [ No CAS ]

References: [1]Journal of Organic Chemistry,1996,vol. 61,p. 14 - 15.

11
[ 122194-07-4 ]
[ 87418-87-9 ]
2',3'-di-O-tert-butyldimethylsilyluridin-5'-yl dimethyl phosphite [ No CAS ]

References: [1]Tetrahedron,1996,vol. 52,p. 1027 - 1034.

12
[ 81246-80-2 ]
[ 122194-07-4 ]
Phosphorous acid (2R,3R,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-(tert-butyl-dimethyl-silanyloxy)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester dimethyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,1996,vol. 61,p. 6273 - 6281.

13
[ 122194-07-4 ]
[ 118849-17-5 ]
Phosphorous acid (2R,3S,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-(2,2,2-trifluoro-acetylamino)-tetrahydro-furan-3-yl ester dimethyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,1996,vol. 61,p. 6273 - 6281.

14
[ 288-94-8 ]
[ 122194-07-4 ]
[ 108-18-9 ]
dimethyl tetrazolylphosphite [ No CAS ]

References: [1]Journal of the Chemical Society. Perkin Transactions 2 (2001),1998,p. 1621 - 1628.

15
[ 67-56-1 ]
[ 921-26-6 ]
[ 122194-07-4 ]

Yield	Reaction Conditions	Operation in experiment
42%	With triethylamine; In tetrahydrofuran; for 0.333333h;Inert atmosphere; Cooling with ice;	Synthesis of 3-9, the resulting yellow solution was spin evaporated directly added triethylamine 47mL (325mmol, 32.9g), 250mL of tetrahydrofuran and stirred to give a yellow suspension. In the dropping funnel was added anhydrous methanol 13mL (322mmol, 10.3g), nitrogen ice-salt bath was added dropwise methanol within 20min, 150mL of tetrahydrofuran wash dropping funnel. After dropping to give a white suspension. The ice bath was removed, stirred for 2h, allowed to stand for a few minutes, filtered off with suction to obtain yellow liquid with a pale pink solid. Wash a small amount of tetrahydrofuran solid. Tetrahydrofuran was removed by rotary evaporation. 5% sodium bicarbonate was poured into 10mL, 20mL and extracted three times with dichloromethane and the combined organic phase, methylene chloride was removed by rotary evaporation, distillation under reduced pressure pumps, taking 78 stable fraction. To give a colorless liquid and a white solid within a condenser tube, identified as the same substance, the collection can be combined, yield 16.68 g, 42% yield.

References: [1]Journal of the Chemical Society. Perkin Transactions 2 (2001),1998,p. 1621 - 1628.
[2]Patent: CN102977145,2017,B .Location in patent: Paragraph 0184; 0185.

16
[ 67-56-1 ]
[ 56183-63-2 ]
[ 122194-07-4 ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 6167 - 6172.

17
[ 89619-03-4 ]
[ 122194-07-4 ]
[ 302808-96-4 ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 6167 - 6172.

18
[ 122194-07-4 ]
[ 2592-95-2 ]
phosphorous acid benzotriazol-1-yl ester dimethyl ester [ No CAS ]

References: [1]Tetrahedron Letters,2004,vol. 45,p. 979 - 982.

19
[ 122194-07-4 ]
[ 26198-21-0 ]
phosphorous acid dimethyl ester 6-trifluoromethyl-benzotriazol-1-yl ester [ No CAS ]

References: [1]Tetrahedron Letters,2004,vol. 45,p. 979 - 982.

20
[ 288-94-8 ]
[ 122194-07-4 ]
[ 688341-33-5 ]
methyl 4-deoxy-2,6-di-O-benzyl-3-keto-α-D-galactopyranoside [ No CAS ]
Phosphorous acid (4S,5R,6S)-5-benzyloxy-2-benzyloxymethyl-6-methoxy-2-tetrazol-1-yl-tetrahydro-pyran-4-yl ester dimethyl ester [ No CAS ]
C₃₀H₄₈N₄O₉P₂ [ No CAS ]

References: [1]Organic Letters,2004,vol. 6,p. 1365 - 1368.

21
[ 122194-07-4 ]
[ 2592-95-2 ]
phosphoric acid benzotriazol-1-yl ester dimethyl ester [ No CAS ]

References: [1]Journal of the American Chemical Society,2004,vol. 126,p. 10884 - 10896.

22
[ 122194-07-4 ]
[ 657357-51-2 ]
[ 868367-88-8 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 8122 - 8129.

23
[ 122194-07-4 ]
[ 657357-49-8 ]
[ 868367-89-9 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 8122 - 8129.

24
[ 922712-28-5 ]
[ 122194-07-4 ]
[ 922712-30-9 ]

References: [1]Journal of the American Chemical Society,2006,vol. 128,p. 16464 - 16465.

25
[ 922712-50-3 ]
[ 122194-07-4 ]
[ 922712-36-5 ]

References: [1]Journal of the American Chemical Society,2006,vol. 128,p. 16464 - 16465.

26
[ 122194-07-4 ]
[ 343925-61-1 ]
acetic acid 3-acetoxy-2-acetoxymethyl-5-acetylamino-6-(dimethoxy-thiophosphoryl)-tetrahydro-pyran-4-yl ester [ No CAS ]
acetic acid 3-acetoxy-2-acetoxymethyl-5-acetylamino-6-(dimethoxy-phosphorylsulfanyl)-tetrahydro-pyran-4-yl ester [ No CAS ]

References: [1]Tetrahedron Letters,2007,vol. 48,p. 1945 - 1949.

27
C₂₃H₃₃N₅O₈Si [ No CAS ]
[ 122194-07-4 ]
C₂₅H₃₈N₅O₁₀SiP [ No CAS ]

References: [1]Journal of the American Chemical Society,2007,vol. 129,p. 7010 - 7011.

28
[ 108-18-9 ]
(+-)-chloroacetic acid-<<β-(2,4-dimethyl-phenoxy)-isopropyl>-methyl-amide> [ No CAS ]
[ 122194-07-4 ]

References: [1]Journal of the Chemical Society. Perkin Transactions 2 (2001),1998,p. 1621 - 1628.

29
[ 4132-28-9 ]
[ 122194-07-4 ]
[ 148171-71-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 4,5-dichloroimidazole; In dichloromethane; at 20℃; for 1.75h;	A mixture of 2, 3,4, 6-tetra-D-benzyl-D-mannose (Koto et al., 1976) (940 mg, 1.74 mmol), dimethoxy-N, N-diisopropylphosphoromidate (437 mg, 2.27 mmol) and 4,5-dichloroimidazole (355 mg, 2.61 mmol) in dry dichloromethane (25 mL), under nitrogen, was stirred at room temperature for 105 min. The mixture was poured into water (100 mL) and extracted with dichloromethane. The organic layer was washed with water, dried over magnesium sulfate and the solvent was removed. The residue consisting mainly of phosphite 10 was used without further purification.

References: [1]Patent: WO2005/49631,2005,A1 .Location in patent: Page/Page column 30.

30
[ 122194-07-4 ]
[ 164221-12-9 ]
[ 1192949-29-3 ]