Home Cart 0 Sign in  
X

[ CAS No. 65766-32-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 65766-32-7
Chemical Structure| 65766-32-7
Chemical Structure| 65766-32-7
Structure of 65766-32-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 65766-32-7 ]

Related Doc. of [ 65766-32-7 ]

Alternatived Products of [ 65766-32-7 ]

Product Details of [ 65766-32-7 ]

CAS No. :65766-32-7 MDL No. :MFCD09702146
Formula : C5H6ClN3 Boiling Point : -
Linear Structure Formula :- InChI Key :WZVLJUBTIWFTIE-UHFFFAOYSA-N
M.W : 143.57 Pubchem ID :309479
Synonyms :

Calculated chemistry of [ 65766-32-7 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.2
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 36.35
TPSA : 37.81 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.13 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.49
Log Po/w (XLOGP3) : 1.48
Log Po/w (WLOGP) : 0.98
Log Po/w (MLOGP) : 0.33
Log Po/w (SILICOS-IT) : 1.24
Consensus Log Po/w : 1.11

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.09
Solubility : 1.17 mg/ml ; 0.00813 mol/l
Class : Soluble
Log S (Ali) : -1.88
Solubility : 1.89 mg/ml ; 0.0132 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.68
Solubility : 0.298 mg/ml ; 0.00207 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.55

Safety of [ 65766-32-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H317-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 65766-32-7 ]

* 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 [ 65766-32-7 ]
  • Downstream synthetic route of [ 65766-32-7 ]

[ 65766-32-7 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 1193-21-1 ]
  • [ 593-51-1 ]
  • [ 65766-32-7 ]
YieldReaction ConditionsOperation in experiment
78% With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 14 h; Into a 100-mL round-bottom flask, was placed N,N-dimethylformamide (10 mL), 4,6- dichloropyrimidine (1 g, 6.71 mmol, 1 equiv), CS2CO3 (4.4 g, 13.50 mmol, 2.01 equiv), methanamine hydrochloride (905 mg, 13.40 mmol, 2.00 equiv). The resulting solution was stirred for 14 h at 80 °C. The resulting solution was diluted with 10 mL of H2O. The resulting solution was extracted with 4x10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1x10 mL of H2O. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 1). This resulted in 750 mg (78percent) of as a white solid. Analytical Data: LC-MS: (ES, m/z): RT = 0.476min, LCMS 32: m/z = 144 [M+l].
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 7, p. 1514 - 1524
[2] European Journal of Organic Chemistry, 2014, vol. 2014, # 7, p. 1514 - 1524
[3] Patent: WO2017/181177, 2017, A1, . Location in patent: Paragraph 0950-0953
[4] Tetrahedron, 2007, vol. 63, # 25, p. 5394 - 5405
  • 2
  • [ 1193-21-1 ]
  • [ 74-89-5 ]
  • [ 65766-32-7 ]
YieldReaction ConditionsOperation in experiment
97.43% at 0 - 20℃; A mixture of 79 (0.50g, 3.36mmol) and IPA (1.5ml) was stirred for a while and then 2M methylamine in THF (4.2ml, 8.40mmol) was added thereto at 0 °C. The resulting mixture was back to room temperature under stirring for overnight. The reaction was quenched by water and then the mixture was extracted by ethyl acetate (30ml x 3). The residue was purified by flash column over silica gel (ethyl acetate: n-Hexane = 1 :2, Rf = 0.20) to afford 83 (0.47g, 97.43percent) as a pale yellow solid. 1H-NMR (300MHz, CDCl3): δ 2.95 (d, J= 5.1 Hz, 3H), 5.26 (br, 1H), 6.34 (s, 1H), 8.34 (s, 1H).
93% With triethylamine In tetrahydrofuran at 20℃; for 23 h; Cooling with ice To a solution of 4,6-dichloropyrimidine (0.50 g) in tetrahydrofuran (0.84 mL), triethylamine (0.94 mL) was added,then a 2.0 mol/L solution of methylamine in tetrahydrofuran (1.7 mL) was added dropwise under ice cooling, and themixture was stirred at room temperature for 23 hours. The reaction solution was concentrated, and then, the obtaine dresidue was purified by silica gel column chromatography (MORITEX Purif Pack-NH, chloroform) to obtain the titlecompound (0.45 g, 93percent) as a colorless solid.1H NMR (300 MHz, CDCl3) δ ppm 2.96 (d, J=5.0Hz, 3H), 6.35 (s, 1H), 8.35 (s, 1H). MS (+): 144 [M+H]+.
93% at 20℃; for 15 h; Take 4,6-dichloropyrimidine (75.7 g, 0.51 mol),Isopropanol (0.98 L) and methylamine/tetrahydrofuran solution (2 mol/L, 0.76 L, 1.52 mol) were added.Stir at room temperature for 15 hours. The reaction was completely monitored by TLC, the reaction mixture was filtered, and the filtrate was concentrated.Distilled water (500 mL) and EA (300 mL) were added, liquid separation, aqueous phase EA extraction (300 mL×2), and the organic phase was combined.Wash with saturated aqueous sodium chloride solution, dry over anhydrous sodium sulfate,Beat with ethyl acetate: petroleum ether (1:30, 800 mL),After drying, a brown solid (68.0 g, yield 93percent) was obtained.
91% at 25℃; for 1 h; General procedure: To a suspension of 4,6-dichloropyrimidine 53 (3.0 g, 20 mmol) in isopropanol (40 mL) was added appropriate amine at such a rate that the internal temperature did not rise above 40 °C. After completion of the addition, the reaction mixture was stirred for 1 h at 25 °C. Water (30 mL) was added, and the resulting suspensio nwas cooled in an ice bath to 0 °C. The precipitated product was filtered off and washed with cold isopropanol/water (2:1, 50 mL) and water. The collected material was dried in vacuo to afford the title compounds.
88% at 20℃; 4,6-Dichloropyrimidine (10 g, 67 mmol) was dissolved in 100 ml isopropanol and the solution was cooled to 0 00 reprecipitating. Methylamine solution (33percent w/w, 17 ml, 140 mmol) was added slowly with stirring and the mixture was stirred overnight atroom temperature. The mixture was evaporated under reduced pressure. The residue was resuspended in water, stirred for 15 mm and then filtered. The solid was dried under reduced pressure. The filtrate was extracted three times with ethyl acetate. The combined organics were dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure. The solid obtained was combined with the firstprecipitate to give 8.50 g (59 mmol, 88percent yield) of the title compound as a white solid. Purity 87percent.1H NMR (300 MHz, CHLOROFORM-d) ö ppm 8.40 (s, 1H), 6.38 (s, 1H), 2.98 (d, 3H, J = 5.1 Hz).UPLC/MS (3 mm) retention time 0.74 mm.LRMS: m/z 144 (M+1, ixOl).
87% at -40 - 0℃; for 4 h; 6-Chloro-N-methylpyrimidin-4-amine (16)[00404] To a solution of 4,6-dichloropyrimidine (5.0 g, 33.79 mmol) in anhydrous THF (50 mL) was slowly added 2.0 M methylamine solution in THF (42.2 mL, 84.48 mmol) at -40 °C. The reaction mixture was stirred at 0 °C for 4 h and partitioned between CHCl3/2- propanol (4/1) and water. The organic layer was dried over anhydrous sodium sulfate, filtered through a pad of CELITE, and concentrated under reduced pressure. The white solid 6- chloro-N-methylpyrimidin-4-amine (4.2 g, 87percent yield) was used in the next reaction without purification. Rt = 1.55 min;1H NMR 600 MHz (CDCl3) 8.13 (br, 1H), 6.54 (m, 1H), 5.37 (br, 1H), 2.99 (m, 3H) ppm; MS m/z: 144.05 [M+1].
86% at 20℃; for 1 h; [0174] To a suspension of 4,6-dichloropyrimidine (0.50 g, 3.4 mmol) in propan-2-ol (10 mL) was added dropwise methylamine (2 M, 3.4 mL). After addition was completed, the reaction mixture was stirred at room temperature for 1 hour. Upon completion, the reaction mixture was concentrated in vacuo. The residue was dissolved with dichloromethane (50 mL), washed with water (10 mL), brine (2x 10 mL) sequentially. The organic phase was collected and concentrated to give 6-chloro-N-methylpyrimidin-4-amine (0.42 g, 86percent yield) as a white solid.
82% at 0 - 5℃; Example J cr ^ ^N'CH3 H6-Chloro-Af-methylpyrimidin-4-amine; [00252] 4,6-Dichloropyrimidine (978 mg, 6.56 mmol) was taken up in isopropanol(1O mL, 131 mmol) and cooled to 0-5 0C. A solution of 33percent methylamine in ethanol (1.768 mL, 13.2 mmol) was added, and the reaction mixture was stirred for 15 hours. The mixture was concentrated under reduced pressure and suspended in water. The title compound was obtained after filtration and drying in vacuo (772 mg, 82percent). 1H NMR (400 MHz, DMSO- d6) δ 8.27 (s, IH), 7.65 (s, IH), 6.50 (s, IH), 2.99 - 2.67 (m, 3H). LC/MS: m/z 144.1 [M+l].
62% at 20℃; for 18 h; e. ( 6-Ch loro-pyrimidin~4~yl)~methyl-amine To a solution of 4,6-dic oro-pyrimidine (7.45 g, 50 mmol) in iPrOH (50 mL) was added a solution of methyl amine in THF (2M, 30 mL, 60 mmol) at room temperature. The resulting mixture was stirred for 18 hours. The mixture was concentrated and the residue was purified by flash chromatography on silica eiuting with DCM:EtOAc = 6:1-1 :1 to obtain the title compound (4.4 g, yield: 62percent) as a white solid. lU NMR (400 MHz, CDC13) δ 2.96 (d, 3H), 5.22-5.36 (bs, 1H), 6.35 (s, 1H), 8.35 (s, 1H); MS (ESI): 144 [M+H]+.
62% at 20℃; for 18 h; To a solution of 4,6-dichloro-pyrimidine (7.45 g, 50 mmol) in iPrOH (50 mL) was added a solution of methyl amine in THF (2M, 30 mL, 60 mmol) at room temperature. The resulting mixture was stirred for 18 hours. The mixture was concentrated and the residue was purified by flash chromatography on silica eluting with DCM:EtOAc = 6: 1—1 : 1 to obtain the title compound (4.4 g, yield: 62percent) as a white solid. 1H-NMR (400 MHz, CDC13) δ 2.96 (d, 3H), 5.22-5.36 (bs, 1H), 6.35 (s, 1H), 8.35 s, 1H); MS (ESI): 144 [M+H]+.
62% at 20℃; for 2 h; General procedure: A solution of 4,6-dichloropyrimidine (20.14 mmol, 3.0 g) (A1) in 20 ml of isopropanol was slowly added dropwise to 10 ml of aqueous ammonia or methylamine or ethylamine at room temperature for 2 h. The solvent was evaporated under reduced pressure, Solid, adding 20 ml of water stirring filter, filter cake washed with water, vacuum drying, in intermediate A2 or A3.4 - methylamino -6 - chloro pyrimidine (A2), the white crystal, yield 62percent.

Reference: [1] Patent: WO2017/15400, 2017, A1, . Location in patent: Paragraph 0044; 0059
[2] Patent: EP3173408, 2017, A1, . Location in patent: Paragraph 0320; 0321
[3] Patent: CN108239069, 2018, A, . Location in patent: Paragraph 0110; 0113-0116
[4] European Journal of Medicinal Chemistry, 2014, vol. 75, p. 11 - 20
[5] Patent: WO2017/64068, 2017, A1, . Location in patent: Page/Page column 40; 41
[6] Patent: WO2016/23014, 2016, A2, . Location in patent: Paragraph 00403-00404
[7] Journal of Medicinal Chemistry, 2011, vol. 54, # 20, p. 7066 - 7083
[8] Patent: WO2018/191587, 2018, A1, . Location in patent: Paragraph 0173; 0174
[9] Patent: WO2011/25965, 2011, A1, . Location in patent: Page/Page column 43-44
[10] Journal of Medicinal Chemistry, 2012, vol. 55, # 6, p. 2869 - 2881
[11] Patent: WO2015/57938, 2015, A1, . Location in patent: Page/Page column 36
[12] Patent: WO2016/164754, 2016, A1, . Location in patent: Page/Page column 34
[13] Patent: CN106045918, 2016, A, . Location in patent: Paragraph 0093; 0094; 0095; 0096
[14] Journal of Applied Chemistry, 1955, vol. 5, p. 358,362
[15] Patent: WO2006/420, 2006, A1, . Location in patent: Page/Page column 161; 229-230
[16] Patent: WO2006/420, 2006, A1, . Location in patent: Page/Page column 245-246
[17] Patent: WO2006/420, 2006, A1, . Location in patent: Page/Page column 248-249
[18] Patent: WO2008/42639, 2008, A1, . Location in patent: Page/Page column 78
[19] Patent: US2007/49592, 2007, A1, . Location in patent: Page/Page column 39
[20] Tetrahedron, 2012, vol. 68, # 10, p. 2294 - 2298
[21] Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1819 - 1825
[22] Patent: WO2017/60488, 2017, A1, . Location in patent: Page/Page column 62; 63
[23] Patent: WO2008/42639, 2008, A1, . Location in patent: Page/Page column 78
  • 3
  • [ 32998-03-1 ]
  • [ 65766-32-7 ]
Reference: [1] Patent: DE839640, 1949, ,
[2] DRP/DRBP Org.Chem.,
[3] DRP/DRBP Org.Chem.,
[4] Patent: US2585906, 1949, ,
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 65766-32-7 ]

Chlorides

Chemical Structure| 31058-83-0

[ 31058-83-0 ]

6-Chloro-N,N-dimethylpyrimidin-4-amine

Similarity: 0.94

Chemical Structure| 5305-59-9

[ 5305-59-9 ]

6-Chloropyrimidin-4-amine

Similarity: 0.91

Chemical Structure| 5621-01-2

[ 5621-01-2 ]

6-Chloro-N,2-dimethylpyrimidin-4-amine

Similarity: 0.88

Chemical Structure| 1005-37-4

[ 1005-37-4 ]

6-Chloro-N4-methylpyrimidine-2,4-diamine

Similarity: 0.87

Chemical Structure| 32998-03-1

[ 32998-03-1 ]

2,6-Dichloro-N-methylpyrimidin-4-amine

Similarity: 0.85

Amines

Chemical Structure| 31058-83-0

[ 31058-83-0 ]

6-Chloro-N,N-dimethylpyrimidin-4-amine

Similarity: 0.94

Chemical Structure| 5305-59-9

[ 5305-59-9 ]

6-Chloropyrimidin-4-amine

Similarity: 0.91

Chemical Structure| 5621-01-2

[ 5621-01-2 ]

6-Chloro-N,2-dimethylpyrimidin-4-amine

Similarity: 0.88

Chemical Structure| 1005-37-4

[ 1005-37-4 ]

6-Chloro-N4-methylpyrimidine-2,4-diamine

Similarity: 0.87

Chemical Structure| 32998-03-1

[ 32998-03-1 ]

2,6-Dichloro-N-methylpyrimidin-4-amine

Similarity: 0.85

Related Parent Nucleus of
[ 65766-32-7 ]

Pyrimidines

Chemical Structure| 31058-83-0

[ 31058-83-0 ]

6-Chloro-N,N-dimethylpyrimidin-4-amine

Similarity: 0.94

Chemical Structure| 5305-59-9

[ 5305-59-9 ]

6-Chloropyrimidin-4-amine

Similarity: 0.91

Chemical Structure| 5621-01-2

[ 5621-01-2 ]

6-Chloro-N,2-dimethylpyrimidin-4-amine

Similarity: 0.88

Chemical Structure| 1005-37-4

[ 1005-37-4 ]

6-Chloro-N4-methylpyrimidine-2,4-diamine

Similarity: 0.87

Chemical Structure| 32998-03-1

[ 32998-03-1 ]

2,6-Dichloro-N-methylpyrimidin-4-amine

Similarity: 0.85