309947-86-2|tert-Butyl N-tert-butoxycarbonyl-N-(7H-purin-6-yl)carbamate| Ambeed

CAS No. :	309947-86-2
Formula :	C₁₅H₂₁N₅O₄
M.W :	335.36
SMILES Code :	O=C(OC(C)(C)C)N(C(OC(C)(C)C)=O)C1=C2NC=NC2=NC=N1
MDL No. :	MFCD17676144
InChI Key :	WNOSWAQZBWMIGM-UHFFFAOYSA-N
Pubchem ID :	10497007

Safety of [ 309947-86-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 309947-86-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	24
Num. arom. heavy atoms	9
Fraction Csp3	0.53
Num. rotatable bonds	7
Num. H-bond acceptors	7.0
Num. H-bond donors	1.0
Molar Refractivity	87.77
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	110.3 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.52
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	2.35
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.03
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.	0.92
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	0.98
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.96

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.22
Solubility	0.204 mg/ml ; 0.000609 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-4.31
Solubility	0.0166 mg/ml ; 0.0000494 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	-3.27
Solubility	0.179 mg/ml ; 0.000535 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	No
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	Yes
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	Yes
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	Yes
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.	-6.68 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	0.0
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<0.0
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)	3.05

Application In Synthesis of [ 309947-86-2 ]

* 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 [ 309947-86-2 ]

[ 309947-86-2 ] Synthesis Path-Downstream 1~54

1
[ 309947-86-2 ]
[ 309947-88-4 ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 7697 - 7699.

2
[ 309947-84-0 ]
[ 309947-86-2 ]

Yield	Reaction Conditions	Operation in experiment
79.5%	With sodium hydrogencarbonate; In methanol; at 50℃; for 0.5h;	Sb2 (500mg, 1.1mmol) was dissolved in methanol (13ml), then added (6.5ml) of saturated NaHCO3 solution, then placed in an oil bath at 50 C for 0.5h, after TLC detection reaction was completed, diluted with plenty of EA water Wash twice, then wash twice with saturated NaCl, dry Na2SO4, concentrate, top column, and quickly pass through the column with (PE/EA=1:1).The white solid product S2 (306.1 mg, 79.5%) was obtained.
	With sodium hydrogencarbonate; In methanol; at 50℃; for 2h;	Step 2: The above residue was solved in 20 mL methanol, which was followed by adding 20% sodium bicarbonate solution (4 mL), the mixture was stirred at 50 C for 2 hrs, which was then purified by a flash chromatography (PE/EA=6/1) to give white solid as the desired product. NMR (400 MHz, DMSO) delta: 13.70 (s, 1H), 8.79 (s, 1H), 8.64 (s, 1H), 1.37 (s, 18H). LC-MS: m/z 336.4 (M+H)+

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 7697 - 7699.
[2]European Journal of Organic Chemistry,2008,p. 5786 - 5797.
[3]Tetrahedron,2007,vol. 63,p. 9836 - 9841.
[4]Chemistry - A European Journal,2009,vol. 15,p. 6244 - 6257.
[5]Patent: CN109912672,2019,A .Location in patent: Paragraph 0084-0085; 0087.
[6]Tetrahedron Letters,2010,vol. 51,p. 2948 - 2950.
[7]Patent: WO2015/123365,2015,A1 .Location in patent: Page/Page column 125.

3
[ 5720-05-8 ]
[ 309947-86-2 ]
di(tert-butyl) 9-p-tolyl-9H-purin-6-yliminodicarbonate [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.

4
[ 5467-74-3 ]
[ 309947-86-2 ]
di(tert-butyl) 9-(4-bromophenyl)-9H-purin-6-yliminodicarbonate [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.

5
[ 5122-99-6 ]
[ 309947-86-2 ]
[ 917081-91-5 ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 2067 - 2077.

6
[ 5720-07-0 ]
[ 309947-86-2 ]
di(tert-butyl) 9-(4-methoxyphenyl)-9H-purin-6-yliminodicarbonate [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.

7
[ 129423-29-6 ]
[ 309947-86-2 ]
di(tert-butyl) 9-(3-phenylprop-1-enyl)-9H-purin-6-yliminodicarbonate [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.

8
2,4,5-trimethylphenylboronic acid [ No CAS ]
[ 309947-86-2 ]
di(tert-butyl) 9-(2,4,5-trimethylphenyl)-9H-purin-6-yliminodicarbonate [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.

9
[ 309947-86-2 ]
[ 98-80-6 ]
di(tert-butyl) 9-phenyl-9H-purin-6-yliminodicarbonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper diacetate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 96h;Molecular sieve;	General procedure: To a solution of 3 (100 mg, 0.30 mmol), phenylboronic acid (75 mg, 0.61mmol), andtriethylamine (60 muL), in dry DMF (1.5 mL) was added copper (II) acetate (90 mg, 0.50 mmol)and 5A molecular sieves (300 mg). The resulting mixture was stirred for 4 days at ambienttemperature under air. Volatiles were evaporated and the crude material was re-dissolved in dryMeOH (3.0 mL). To this solution K2CO3 (100mg, 0.72 mmol) was added and the mixture wasstirred for 12 h at ambient temperature. Volatiles were evaporated and the crude was partitioned(CH2Cl2//H2O). The organic layer was separated and dried over Na2SO4. Flash chromatography(70% EtOAc/Hexanes) gave 6a (30 mg, 0.10 mmol, 33%). 1H NMR (CDCl3, 500MHz) delta 8.84 (s,1H), 8.24 (s, 1H), 8.15 (bs, 1H), 7.74 (d, J = 8.0, 2H), 7.62 (t, J = 7.5, 2H), 7.51 (t, J = 7.5, 1H),1.60 (s, 9H); 13C NMR (CDCl3, 125MHz) delta 153. 7, 150.3, 149.7, 141.3, 134.3, 130.0, 128.6,123.5, 82.4, 28.2; HRMS = [M+H] 312.1456; C16H18N5O2 = 312.1460.

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.
[2]Tetrahedron Letters,2015,vol. 56,p. 6574 - 6576.

10
[ 877651-72-4 ]
[ 309947-86-2 ]
C₂₃H₃₃N₅O₆ [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

11
[ 96-41-3 ]
[ 309947-86-2 ]
C₂₀H₂₉N₅O₄ [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.
[2]Tetrahedron Letters,2010,vol. 51,p. 2948 - 2950.

12
[ 60410-16-4 ]
[ 309947-86-2 ]
C₂₂H₂₉N₅O₆ [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

13
[ 163226-45-7 ]
[ 309947-86-2 ]
(1R,4R,5S)-9-N-[3-(trityloxymethyl)-4,5-O,O-isopropylidene-2-cyclopenten-L-yl]N₆,N₆-bis-(tert-butoxycarbonyl)adenine [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

14
[ 185622-63-3 ]
[ 309947-86-2 ]
C₂₃H₃₁N₅O₆ [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

15
[ 309947-86-2 ]
[ 698999-23-4 ]
C₂₅H₃₅N₅O₆ [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

16
[ 303963-93-1 ]
[ 309947-86-2 ]
[ 952418-11-0 ]

References: [1]Tetrahedron,2007,vol. 63,p. 9836 - 9841.

17
[ 24424-99-5 ]
[ 309947-86-2 ]

References: [1]Tetrahedron,2007,vol. 63,p. 9836 - 9841.
[2]Journal of Organic Chemistry,2000,vol. 65,p. 7697 - 7699.
[3]Patent: WO2015/123365,2015,A1 .
[4]Patent: CN109912672,2019,A .

18
[ 66224-66-6 ]
[ 309947-86-2 ]

References: [1]Tetrahedron,2007,vol. 63,p. 9836 - 9841.
[2]Journal of Organic Chemistry,2000,vol. 65,p. 7697 - 7699.
[3]Patent: WO2015/123365,2015,A1 .
[4]Patent: CN109912672,2019,A .

19
[ 309947-86-2 ]
[ 72877-50-0 ]

References: [1]Tetrahedron,2007,vol. 63,p. 9836 - 9841.

20
[ 309947-86-2 ]
neplanocin A [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

21
[ 309947-86-2 ]
[ 111005-70-0 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

22
[ 309947-86-2 ]
[ 125409-63-4 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

23
[ 309947-86-2 ]
[ 158799-95-2 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 9187 - 9189.

24
[ 309947-86-2 ]
N⁹-(4-bromophenyl)adenine [ No CAS ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.

25
[ 309947-86-2 ]
[ 127820-21-7 ]

References: [1]Journal of Organic Chemistry,2006,vol. 71,p. 9183 - 9190.

26
(+/-)-t-1-(tert-butyldiphenylsilyloxy)methyl-4-hydroxy-7-oxabicyclo-[3.3.0]oct-2-ene-8-one [ No CAS ]
[ 309947-86-2 ]
C₂₉H₃₁N₅O₃Si [ No CAS ]

References: [1]Tetrahedron,2008,vol. 64,p. 1494 - 1505.

27
[ 1009810-92-7 ]
[ 309947-86-2 ]
C₂₆H₃₆FN₅O₆ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 220 - 222.

28
[ 309947-86-2 ]
[ 5437-45-6 ]
[ 1108637-35-9 ]

References: [1]European Journal of Organic Chemistry,2008,p. 5786 - 5797.

29
[ 1150503-06-2 ]
[ 309947-86-2 ]
[ 1150502-75-2 ]

References: [1]European Journal of Organic Chemistry,2009,p. 1082 - 1092.

30
[ 1192851-94-7 ]
[ 309947-86-2 ]
N-[9-(2,4-bis(benzyloxy)-5-cyclohexylmethoxy-benzyl)-9H-purin-6-yl]-N-(2,2-dimethyl-propionyl)-2,2-dimethylpropionamide [ No CAS ]