60186-89-2|4-Bromo-2,6-dimethoxypyrimidine| Ambeed

CAS No. :	60186-89-2
Formula :	C₆H₇BrN₂O₂
M.W :	219.04
SMILES Code :	COC1=CC(Br)=NC(OC)=N1
MDL No. :	MFCD07787454
InChI Key :	BFHOSMVQVHFCSK-UHFFFAOYSA-N
Pubchem ID :	11287431

Safety of [ 60186-89-2 ]

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

Computational Chemistry of [ 60186-89-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.33
Num. rotatable bonds	2
Num. H-bond acceptors	4.0
Num. H-bond donors	0.0
Molar Refractivity	42.72
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	44.24 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.41
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	1.84
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.26
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.	0.68
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	1.54
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.54

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.63
Solubility	0.515 mg/ml ; 0.00235 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.	-2.39
Solubility	0.893 mg/ml ; 0.00408 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	-2.77
Solubility	0.375 mg/ml ; 0.00171 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	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	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.	-6.33 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	0.0 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)	2.3

Application In Synthesis of [ 60186-89-2 ]

* 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 [ 60186-89-2 ]

[ 60186-89-2 ] Synthesis Path-Downstream 1~54

1
[ 2314-97-8 ]
[ 60186-89-2 ]
[ 76513-87-6 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 2755 - 2761.

4
[ 52517-92-7 ]
[ 60186-89-2 ]
[ 299966-38-4 ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

5
[ 107428-20-6 ]
[ 60186-89-2 ]
(+/-)-3-allyl-5-[(Z)-(2,6-dimethoxy-4-pyrimidinyl)methylene]dihydro-2(3H)-furanone [ No CAS ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

6
[ 60186-89-2 ]
[ 299966-60-2 ]
[ 299966-61-3 ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

7
[ 60186-89-2 ]
[ 434308-68-6 ]
[ 434308-70-0 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

8
[ 36847-11-7 ]
[ 124-41-4 ]
[ 60186-89-2 ]

References: [1]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.
[2]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

9
[ 946572-98-1 ]
[ 60186-89-2 ]
[ 946572-99-2 ]

References: [1]Synlett,2007,p. 1446 - 1448.

10
[ 959434-63-0 ]
[ 60186-89-2 ]
C₂₇H₃₉F₂N₅O₆ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5806 - 5811.

11
[ 60186-89-2 ]
[ 946573-00-8 ]

References: [1]Synlett,2007,p. 1446 - 1448.

12
[ 60186-89-2 ]
C₄₀H₄₃N₅O₈ [ No CAS ]

References: [1]Synlett,2007,p. 1446 - 1448.

13
[ 60186-89-2 ]
[ 434308-78-8 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

14
[ 60186-89-2 ]
[ 434308-58-4 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

15
[ 60186-89-2 ]
[ 434309-00-9 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

16
[ 60186-89-2 ]
[ 434308-98-2 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

17
[ 60186-89-2 ]
[ 434308-86-8 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

18
[ 60186-89-2 ]
[ 434308-88-0 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

19
[ 60186-89-2 ]
[ 434308-72-2 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

20
[ 60186-89-2 ]
[ 434308-74-4 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

21
[ 60186-89-2 ]
(1'R,2'R)-2,6-dimethoxy-4-(2'-dibenzylamino-1'-hydroxy-4'-trityloxybutyl)pyrimidine [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

22
[ 60186-89-2 ]
(2aS,3R,4S,5aS,7R)-7-[(S)-(tert-Butyl-dimethyl-silanyloxy)-(2,6-dimethoxy-pyrimidin-4-yl)-methyl]-3-methyl-4-triethylsilanyloxy-2,2a,3,4,5,5a,6,7-octahydro-1H-1,8,8b-triaza-acenaphthylene [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

23
[ 60186-89-2 ]
[ 434309-02-1 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

24
[ 60186-89-2 ]
[ 434309-04-3 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

25
[ 60186-89-2 ]
[ 434308-90-4 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

26
[ 60186-89-2 ]
(3R,4aS,6S,7R,8S)-8-Azidomethyl-3-[(S)-(tert-butyl-dimethyl-silanyloxy)-(2,6-dimethoxy-pyrimidin-4-yl)-methyl]-1-methoxy-7-methyl-6-triethylsilanyloxy-4,4a,5,6,7,8-hexahydro-3H-pyrido[1,2-c]pyrimidine [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

27
[ 60186-89-2 ]
[(1R,2S)-1-[(1S,4R,5R,6S)-6-(4-Bromo-benzyloxymethyl)-5-methyl-7-oxa-1-aza-bicyclo[2.2.1]hept-2-ylmethyl]-2-(tert-butyl-dimethyl-silanyloxy)-2-(2,6-dimethoxy-pyrimidin-4-yl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

28
[ 60186-89-2 ]
[ 434308-80-2 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

29
[ 60186-89-2 ]
[ 434308-76-6 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

30
[ 60186-89-2 ]
(4R,5S)-4-Dibenzylamino-5-(2,6-dimethoxy-pyrimidin-4-yl)-dihydro-furan-2-one [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

31
[ 60186-89-2 ]
[ 812646-14-3 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

32
[ 60186-89-2 ]
(3R,4aS,6S,7R,8S)-8-Aminomethyl-3-[(S)-(tert-butyl-dimethyl-silanyloxy)-(2,6-dimethoxy-pyrimidin-4-yl)-methyl]-6-hydroxy-7-methyl-octahydro-pyrido[1,2-c]pyrimidin-1-one [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

33
[ 60186-89-2 ]
(3R,4aS,7R,8S)-8-(4-Bromo-benzyloxymethyl)-3-[(S)-(tert-butyl-dimethyl-silanyloxy)-(2,6-dimethoxy-pyrimidin-4-yl)-methyl]-6-hydroxy-7-methyl-octahydro-pyrido[1,2-c]pyrimidin-1-one [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.
[2]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

34
[ 60186-89-2 ]
[(1R,2S)-1-[(1S,2S,4R,5R,6S)-6-(4-Bromo-benzyloxymethyl)-5-methyl-7-oxa-1-aza-bicyclo[2.2.1]hept-2-ylmethyl]-2-(tert-butyl-dimethyl-silanyloxy)-2-(2,6-dimethoxy-pyrimidin-4-yl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

35
[ 60186-89-2 ]
[(1R,2S)-1-[(2S,5R,6S)-6-(4-Bromo-benzyloxymethyl)-4-hydroxy-5-methyl-piperidin-2-ylmethyl]-2-(tert-butyl-dimethyl-silanyloxy)-2-(2,6-dimethoxy-pyrimidin-4-yl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1963 - 1977.

36
[ 60186-89-2 ]
(2S,3R)-6-[(2R,3S)-2-Amino-3-(tert-butyl-dimethyl-silanyloxy)-3-(2,6-dimethoxy-pyrimidin-4-yl)-propyl]-2-(4-bromo-benzyloxymethyl)-3-methyl-piperidin-4-ol [ No CAS ]

References: [1]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

37
[ 60186-89-2 ]
[(1R,2S)-1-[(5R,6S)-6-(4-Bromo-benzyloxymethyl)-5-methyl-7-oxa-1-aza-bicyclo[2.2.1]hept-2-ylmethyl]-2-(tert-butyl-dimethyl-silanyloxy)-2-(2,6-dimethoxy-pyrimidin-4-yl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

38
[ 60186-89-2 ]
[(1R,2S)-1-[(5R,6S)-6-(4-Bromo-benzyloxymethyl)-4-hydroxy-5-methyl-piperidin-2-ylmethyl]-2-(tert-butyl-dimethyl-silanyloxy)-2-(2,6-dimethoxy-pyrimidin-4-yl)-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Journal of the American Chemical Society,2002,vol. 124,p. 4950 - 4951.

39
[ 60186-89-2 ]
(+/-)-4-[(Z)-(2,6-dimethoxy-4-pyrimidinyl)methylene]tetrahydro-6-propyl-2(1H)-pyrimidinone [ No CAS ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

40
[ 60186-89-2 ]
(+/-)-(4R,6R)-4-[(2,6-dimethoxy-4-pyrimidinyl)methyl]tetrahydro-6-propyl-2(1H)-pyrimidinone [ No CAS ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

41
[ 60186-89-2 ]
[ 299966-63-5 ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

42
[ 60186-89-2 ]
(+/-)-(4R,6R)-4-allyl-6-[(R)-(2,6-dimethoxy-4-pyrimidinyl)hydroxymethyl]tetrahydro-2(1H)-pyrimidinone [ No CAS ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

43
[ 60186-89-2 ]
(+/-)-(4R,6R)-4-allyl-6-[(S)-(2,6-dimethoxy-4-pyrimidinyl)hydroxymethyl]tetrahydro-2(1H)-pyrimidinone [ No CAS ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.
[2]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

44
[ 60186-89-2 ]
[ 299966-69-1 ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

45
[ 60186-89-2 ]
4-Nitro-benzoic acid (R)-((4S,6S)-6-allyl-2-oxo-hexahydro-pyrimidin-4-yl)-(2,6-dimethoxy-pyrimidin-4-yl)-methyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,2000,vol. 65,p. 5668 - 5675.

46
[ 696-62-8 ]
[ 60186-89-2 ]
[ 1233493-56-5 ]

References: [1]Journal of Organic Chemistry,2010,vol. 75,p. 4686 - 4695.

47
[ 51934-41-9 ]
[ 60186-89-2 ]
[ 1233493-52-1 ]

References: [1]Journal of Organic Chemistry,2010,vol. 75,p. 4686 - 4695.

48
[ 98-86-2 ]
[ 60186-89-2 ]
[ 1236194-05-0 ]

References: [1]Journal of Organic Chemistry,2010,vol. 75,p. 5271 - 5277.

49
[ 60186-89-2 ]
[ 1452228-35-1 ]

References: [1]Patent: US2013/225593,2013,A1 .
[2]Patent: WO2014/127816,2014,A1 .
[3]Patent: WO2017/181177,2017,A1 .

50
[ 60186-89-2 ]
[ 1452228-36-2 ]

References: [1]Patent: US2013/225593,2013,A1 .
[2]Patent: WO2014/127816,2014,A1 .
[3]Patent: WO2017/181177,2017,A1 .

51
[ 60186-89-2 ]
[ 1452228-37-3 ]

References: [1]Patent: US2013/225593,2013,A1 .
[2]Patent: WO2014/127816,2014,A1 .
[3]Patent: WO2017/181177,2017,A1 .

52
[ 383-63-1 ]
[ 60186-89-2 ]
1-(2,6-dimethoxypyrimidin-4-yl)-2,2,2-trifluoroethane-1,1-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%		Into a 1-L 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed <strong>[60186-89-2]4-bromo-2,6-dimethoxypyrimidine</strong> (23 g, 105.01 mmol, 1 equiv), tetrahydrofuran (250 mL), Diethyl ether (250 mL). And n-BuLi(2.5M) (46.2 mg, 0.72 mmol, 1.10 equiv) was added dropwise at -78 C. After stirred for 5 min at -78 C, ethyl 2,2,2-trifluoroacetate (16.4 g, 115.43 mmol, 1.10 equiv) was added dropwise. After stirred for 30 min at -78 C, the resulting solution was stirred for overnight at RT. The reaction was then quenched by the addition of 200 mL of saturated NH4CI. Sodium carbonate was employed to adjust the pH to 8. The resulting solution was diluted with 1 L of EA. The resulting mixture was washed with 3x500 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 100- 1 : 10). The collected fractions were combined and concentrated under vacuum. This resulted in 15 g (56%) of the title compound as an off-white solid. Analytical Data: LC-MS: (ES, m/z): RT = 0.739 min, LCMS 32: m/z = 255 [M+l].
		To a solution of <strong>[60186-89-2]4-bromo-2,6-dimethoxy-pyrimidine</strong> (6.80 g, 27.94 mmol) in THF (190 mL) and diethylether (190 mL) n-butyllithium (in hexane/THF, 2.01 g, 30.74 mmol) is added dropwise with stirring at -78 C. After 4 min ethyl trifluoroacetate (4.46 g, 30.74 mmol) in THF (50 mL) is added dropwise at -78 C. The reaction mixture is stirred for 30 min at -78 C. and then the reaction is allowed to warm to room temperature slowly and stirred over night at room temperature. To the reaction mixture 1 N HCl solution is added. The resulting mixture is extracted with EA and washed with sat. sodium chloride solution and water. The organic phase is dried over sodium sulfate, filtered and the solvent is evaporated in vacuo. The residue is purified by flash column chromatography (silica gel, PE/EA=8/2) to give the product.
		To a solution of <strong>[60186-89-2]4-bromo-2,6-dimethoxy-pyrimidine</strong> (6.80 g, 27.94 mmol) in THF (190 mL) and diethylether (190 mL) n-butyllithium (in hexane/THF, 2.01 g, 30.74 mmol) is added dropwise with stirring at -78 C. After 4 min ethyl trifluoroacetate (4.46 g, 30.74 mmol) in THF (50 mL) is added dropwise at -78 C. The reaction mixture is stirred for 30 min at -78 C and then the reaction is allowed to warm to room temperature slowly and stirred over night at room temperature. To the reaction mixture 1 N HCI solution is added . The resulting mixture is extracted with EA and washed with sat. sodium chloride solution and water. The organic phase is dried over sodium sulfate, filtered and the solvent is evaporated in vacuo. The residue is purified by flash col umn chromatography (silica gel, PE / EA = 8 12) to give the product. MS (ESI+): m/z = 255 [M+H]+ TLC (silica gel, PE/EA 3/1 ): Rf = 0.20

References: [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01122; 01128-01130.
[2]Patent: US2013/225593,2013,A1 .Location in patent: Paragraph 0416.
[3]Patent: WO2014/127816,2014,A1 .Location in patent: Page/Page column 81.

53
(R)-5-(1-hydroxy-2-(2,8-diazaspiro[4.5]decan-8-yl)ethyl)-4-methylisobenzofuran-1(3H)-one [ No CAS ]
[ 60186-89-2 ]
(R)-5-(2-(2-(2,6-dimethoxypyrimidin-4-yl)-2,8-diazaspiro[4.5]decan-8-yl)-1-hydroxyethyl)-4-methylisobenzofuran-1(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; at 100℃;Sealed tube;	To a microwave vial was charged (R) -5- (1-hydroxy-2- (2, 8-diazaspiro [4.5] decan-8-yl) ethyl) -4-methylisobenzofuran-1 (3H) -one (40 mg, 0.121 mmol) , 4-bromo-2, 6-dimethoxypyrimidine (26.5 mg, 0.121 mmol) , tris (dibenzylideneacetone) dipalladium (0) (5.54 mg, 6.05 mumol) , 2-dicyclohexylphosphino-2?, 4?, 6?-triisopropylbiphenyl (11.5 mg, 0.024 mmol) , and potassium phosphate (51.4 mg, 0.242 mmol) . The vial was sealed, degased, and filled with dioxane (0.60 mL) . The reaction mixture was heated at 100 overnight, diluted with water, extracted with EtOAc. The organic layer was washed with brined, dried, evaporated to give the crude product, which was purified by silica gel column chromatography (0-10 MeOH/DCM) to afford (R) -5- (2- (2- (2, 6-dimethoxypyrimidin-4-yl) -2, 8-diazaspiro [4.5] decan-8-yl) -1-hydroxyethyl) -4-methylisobenzofuran-1 (3H) -one. LC-MS (ESI, m/z) : 469 [M+1] +.

References: [1]Patent: WO2016/65582,2016,A1 .Location in patent: Page/Page column 71.

54
[ 67-56-1 ]
[ 36847-11-7 ]
[ 60186-89-2 ]

Yield	Reaction Conditions	Operation in experiment
23 g	With sodium methylate; In diethyl ether; at 20℃; for 2h;	Into a 2-L 3-necked round-bottom flask, was placed 2,4,6-tribromopyrimidine (54 g, 170.47 mmol, 1 equiv), methanol (500 mL), diethyl ether (500 mL), and MeONa/MeOH (30%) (76.7 g, 2.50 equiv) was added dropwise. The resulting solution was stirred for 2 h at RT. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 1 L of EA. The resulting mixture was washed with 3x500 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 100-1 : 10). The collected fractions were combined and concentrated under vacuum. This resulted in 23 g (62%) of the title compound as a white solid. Analytical Data: LC-MS: (ES, m/z): RT = 1.287 min, LCMS 28: m/z = 219 [M+l].

References: [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01122; 01125-01127.

Historical Records

Technical Information

• Alkyl Halide Occurrence • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Nomenclature of Ethers • Preparation of Ethers • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Reactions of Ethers • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

Related Functional Groups of
[ 60186-89-2 ]

Bromides

A821227 [959240-72-3]

4-Bromo-2-methoxypyrimidine

Similarity: 0.83

A215406 [1086382-38-8]

4-Bromo-6-hydroxypyrimidine

Similarity: 0.76

A229613 [944709-74-4]

2-Bromo-6-methoxypyrimidine

Similarity: 0.70

A143634 [19752-61-5]

5-Bromo-2,4-di-tert-butoxypyrimidine

Similarity: 0.66

A116042 [14001-66-2]

5-Bromo-2-methoxypyrimidine

Similarity: 0.65

Ethers

A206714 [3551-55-1]

2,4-Dimethoxypyrimidine

Similarity: 0.83

A821227 [959240-72-3]

4-Bromo-2-methoxypyrimidine

Similarity: 0.83

A134719 [186435-66-5]

6-Amino-2-methoxypyrimidin-4-ol

Similarity: 0.72

A249253 [120129-83-1]

2,4-Dimethoxy-5,6-dimethylpyrimidine

Similarity: 0.71

A963559 [6320-15-6]

4-Chloro-2,6-dimethoxypyrimidine

Similarity: 0.71

Related Parent Nucleus of
[ 60186-89-2 ]

Pyrimidines

A206714 [3551-55-1]

2,4-Dimethoxypyrimidine

Similarity: 0.83

A821227 [959240-72-3]

4-Bromo-2-methoxypyrimidine

Similarity: 0.83

A215406 [1086382-38-8]

4-Bromo-6-hydroxypyrimidine

Similarity: 0.76

A134719 [186435-66-5]

6-Amino-2-methoxypyrimidin-4-ol

Similarity: 0.72

A963559 [6320-15-6]

4-Chloro-2,6-dimethoxypyrimidine

Similarity: 0.71

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CAS No.: 60186-89-2

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CAS No.: 60186-89-2

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[ 60186-89-2 ] Synthesis Path-Downstream 1~54

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[ 60186-89-2 ]

Bromides

Ethers

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[ 60186-89-2 ]

Pyrimidines

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CAS No.: 60186-89-2

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CAS No.: 60186-89-2

Alternative Products

Product Details of [ 60186-89-2 ]

Safety of [ 60186-89-2 ]

Computational Chemistry of [ 60186-89-2 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 60186-89-2 ]

[ 60186-89-2 ] Synthesis Path-Downstream 1~54

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 60186-89-2 ]

Bromides

Ethers

Related Parent Nucleus of [ 60186-89-2 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 60186-89-2 ]

Related Parent Nucleus of
[ 60186-89-2 ]