Home Cart 0 Sign in  
X

[ CAS No. 10397-13-4 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 10397-13-4
Chemical Structure| 10397-13-4
Chemical Structure| 10397-13-4
Structure of 10397-13-4 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 10397-13-4 ]

Related Doc. of [ 10397-13-4 ]

Alternatived Products of [ 10397-13-4 ]
Product Citations

Product Details of [ 10397-13-4 ]

CAS No. :10397-13-4 MDL No. :MFCD05022359
Formula : C8H9Cl2N3O Boiling Point : -
Linear Structure Formula :- InChI Key :OXCOCPRVQUEIOL-UHFFFAOYSA-N
M.W : 234.08 Pubchem ID :2772068
Synonyms :

Calculated chemistry of [ 10397-13-4 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.5
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 57.78
TPSA : 38.25 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.16 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.45
Log Po/w (XLOGP3) : 2.21
Log Po/w (WLOGP) : 1.24
Log Po/w (MLOGP) : 1.06
Log Po/w (SILICOS-IT) : 2.2
Consensus Log Po/w : 1.83

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.93
Solubility : 0.272 mg/ml ; 0.00116 mol/l
Class : Soluble
Log S (Ali) : -2.65
Solubility : 0.527 mg/ml ; 0.00225 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.08
Solubility : 0.196 mg/ml ; 0.000836 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.09

Safety of [ 10397-13-4 ]

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

Application In Synthesis of [ 10397-13-4 ]

* 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 [ 10397-13-4 ]
  • Downstream synthetic route of [ 10397-13-4 ]

[ 10397-13-4 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 110-91-8 ]
  • [ 3764-01-0 ]
  • [ 10397-13-4 ]
  • [ 52127-83-0 ]
YieldReaction ConditionsOperation in experiment
79% at 0 - 20℃; for 0.5 h; 2,4,6-Trichloropyrimidine (5) (3.158 g, 17.22 mmol) and acetone (60 mL) were combined and cooledto 0 °C. Morpholine (7) (1.05 eq., 1.576 g, 18.09 mmol) was added and the solution stirred at 0 °C for15 min then warmed to room temperature for another 15 min. The reaction was monitored by TLCanalysis (20percent ethyl acetate in hexanes). The reaction was then concentrated via rotary evaporationand further dried under high vacuum. Product was purified using silica column chromatographywith 20percent ethyl acetate in hexanes as the eluent. 10 (major regioisomer) (3.183 g, 13.6 mmol, 79percent).Elem. anal. for C8H9N3OCl2: C, 41.05 (found 42.27); H, 3.88 (found 4.06). 1H-NMR (300 MHz, CDCl3) δ 6.40 (s, 1H), 3.82–3.70 (m, 4H), 3.65 (m, 4H). HRMS [M]+ calcd. for C8H9N3OCl2, 234.0201; found234.0196. 11 (minor regioisomer) (0.806 g, 3.444 mmol, 20percent). 1H-NMR (300 MHz, chloroform-d) δ 6.56 (s, 1H), 3.85–3.60 (m, 8H). 13C-NMR (101 MHz, chloroform-d) δ 161.75, 160.55, 108.31, 66.59, 44.39.HRMS [M]+ calcd. for C8H9N3OCl2, 234.0201; found 234.0196.
65% at 0 - 20℃; Inert atmosphere A solution of morpholine (22.4 mL, 512.4 mmol, 4.2 eq) in EtOH (100 mL) is added dropwise to a cooled (0°C) solution of 2,4,6-trichloropyrimidine (14 mL, 122 mmol, 1 eq) in EtOH (200 mL). The mixture is stirred at rt overnight. The crude mixture is poured onto a saturated solution of NaHSO4 (1 L), and the resulting precipitate is collected by filtration. The solid is redissolved in a minimal amount of DCM and adsorbed on silica gel. FC (AcOEt Cycl 1 :3→ 1 :1 ) gives the desired compounds 4-(4,6-Dichloropyrimidin-2- yl)morpholine (20percent yield) and 4-(2,6-dichloropyrimidin-4-yl)morpholine (65percent yield). 4-(4,6-Dichloropyrimidin-2-yl)morpholine: 1H NMR (400 MHz, CDCl3): δ 6.53 (s, 1H), 3.1 (m, 4H), 3.71 (m, 4H). 13C NMR (100.6 MHz, CDCl3): δ 161.6, 160.4, 108.2, 66.5, 44.3. 4-(2,6-dichloropyrimidin-4-yl)morpholine: 1H NMR (400 MHz, CDCl3): δ 6.34 (s, 1H), 3.70 (m, 4H), 3.58 (m, 4H). 13C NMR (100.6 MHz, CDCl3): δ 162.9, 160.3, 159.5, 99.6, 66.9, 44.3.
18% With N-ethyl-N,N-diisopropylamine In ethanol at 0 - 20℃; To a solution of 2,4,6-trichloropyrimidine (14.0 mL, 122 mmol, 1 .0 eq.) in EtOH (150 mL) is added a solution of morpholine (1 1 .2 mL, 256 mmol, 2.1 eq.) and N,N- diisopropylethylamine (44.6 mL, 256 mmol, 2.1 eq.) in EtOH (150 mL) dropwise at 0 °C. The reaction mixture is stirred overnight at room temperature and the solvent is removed under reduced pressure. The crude product is extracted with dichloromethane (3 x 100 mL) and the organic phase is successively washed with saturated aqueous sodium bisulfate (3 x 400 mL). The combined organic layers are dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude mixture is purified by flash column chromatography (Si02, cyclohexane / ethyl acetate 9:1 -> 3:1 ) to yield i26 (5.02 g, 18percent) and i27 (16.7 g, 59percent), both as colorless solids. 4-(4,6-dichloropyrimidin-2-yl)morpholine (i26): 1H NMR (400 MHz, CDCI3): δ 6.56 (s, 1 H), 3.78 (m, 4 H) 3.74 (m, 4 H). 4-(2,6-dichloropyrimidin-4-yl)morpholine (i27): 1H NMR (400 MHz, CDCI3): δ 6.41 (s, 1 H), 3.78 (m, 4 H), 3.65 (m, 4 H).
18% With N-ethyl-N,N-diisopropylamine In ethanol at 0 - 20℃; To a solution of 2,4,6-trichloropyrimidine (14.0 mL, 122 mmol, 1.0 eq.) in EtOH (150 mL) is added a solution of morpholine (11.2 mL, 256 mmol, 2.1 eq.) and N,N- diisopropylethylamine (44.6 mL, 256 mmol, 2.1 eq.) in EtOH (150 mL) dropwise at 0 °C. The reaction mixture is stirred overnight at room temperature and the solvent is removed under reduced pressure. The crude product is extracted with dichloromethane (3 x 100 mL) and the organic phase is successively washed with saturated aqueous sodium bisulfate (3 x 400 mL). The combined organic layers are dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude mixture is purified by flash column chromatography (Si02, cyclohexane / ethyl acetate 9: 1 to 3: 1) to yield i26 (5.02 g, 18percent) and i27 (16.7 g, 59percent), both as colorless solids. 4-(4,6-dichloropyrimidin-2-yl)morpholine (i26): 1H NMR (400 MHz, CDC13): δ 6.56 (s, 1 H), 3.78 (m, 4 H) 3.74 (m, 4 H). 4-(2,6-dichloropyrimidin-4-yl)morpholine (i27): 1H NMR (400 MHz, CDC13): δ 6.41 (s, 1 H), 3.78 (m, 4 H), 3.65 (m, 4 H).
18% With N-ethyl-N,N-diisopropylamine In ethanol at 0 - 20℃; To a solution of 2,4,6-trichioropyrimidine (14.0 mL, 122 mmol, 1.0 eq.) in EtOH (150mL) is added a solution of morpholine (11.2 mL, 256 mmol, 2.1 eq.) and N,Ndiisopropylethylamine (44.6 mL, 256 mmol, 2.1 eq.) in EtOH (150 mL) dropwise at 0 °C. The reaction mixture is stirred overnight at room temperature and the solvent is removed under reduced pressure. The crude product is extracted with dichloromethane (3 x 100 mL) and the organic phase is successively washed with saturated aqueous sodium bisulfate (3 x 400 mL).The combined organic layers are dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude mixture is purified by flash column chromatography (Si02, cyclohexane / ethyl acetate 9:1 to 3:1) to yield 126 (5.02 g, 18percent) and 127 (16.7 g, 59percent), both as colorless solids.4-(4,6-dichloropyrimidin-2-yl)morpholine (126): ‘H NMR (400 MHz, CDC13): ö 6.56(s, 1 H), 3.78 (m, 4 H) 3.74 (m, 4 H).4-(2,6-dichloropyrimidin-4-yl)morpholine (127): ‘H NMR (400 MHz, CDC13): ö 6.41 (s, 1 H), 3.78 (m, 4 H), 3.65 (m, 4 H).
12% With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 0 - 20℃; for 24 h; Reference Example 11; (6-Chloro-2-morpholin-4-vI-pyrimidm-4-yl)-(2-pyridin-3-yl- ethvD-amine; To a stirred solution of 2,4,6-trichloropyrimidine (10 ml; 87 mmol), and DIPEA (16 mL; 92 mmol) in dioxane (60 mL) at 5 °C was added morpholine (8 ml; 91 mmol) over 5 minutes (a white solid separates during addition). The reaction mixture was stirred whilst allowing to warm to r.t. overnight (16 h). Volatiles were removed in vacuo, the resulting residue was redissolved (CH2Cl2) and evaporated onto silica and purified by flash <n="22"/>chromatography (90:10 to 50:50 petrol/EtOAc as eluent) to afford the regioisomeric products: 4-(4,6-dichloro-pyrimidin-2-yl)-morpholine (2.46 g; 12 percent); and 4-(2,6-dichloro-pyrimidin-4- yl)-morpholine (9.72 g; 48 percent).

Reference: [1] Molecules, 2018, vol. 23, # 7, p. 1 - 13
[2] Patent: WO2015/49369, 2015, A1, . Location in patent: Page/Page column 48; 49
[3] Patent: WO2016/75130, 2016, A1, . Location in patent: Page/Page column 124-125
[4] Patent: WO2017/198347, 2017, A1, . Location in patent: Page/Page column 88; 89
[5] Patent: WO2017/198346, 2017, A1, . Location in patent: Page/Page column 77; 78
[6] Patent: WO2008/125835, 2008, A1, . Location in patent: Referential example 11
[7] Patent: WO2006/65872, 2006, A1, . Location in patent: Page/Page column 43
[8] Patent: WO2006/53112, 2006, A1, . Location in patent: Page/Page column 50-51
[9] Patent: WO2009/66084, 2009, A1, . Location in patent: Page/Page column 61-62
[10] Patent: WO2006/124662, 2006, A1, . Location in patent: Page/Page column 73
[11] Patent: WO2005/7646, 2005, A1, . Location in patent: Page 46-47
[12] Patent: WO2005/7648, 2005, A2, . Location in patent: Page 62
  • 2
  • [ 5414-19-7 ]
  • [ 56-05-3 ]
  • [ 10397-13-4 ]
YieldReaction ConditionsOperation in experiment
28% With potassium carbonate In DMF (N,N-dimethyl-formamide) for 3 h; Heating / reflux 2-bromoethylether (3.65g), potassium carbonate (8.29g), and N,N-dimethylformamide (75mL) were added to 2-amino-4,6-dichloropyrimidine (2.46g), and the mixture was refluxed for 3 hours while heated. Subsequently, the reaction mixture was diluted with ethyl acetate, was washed with water, and was dried over anhydrous sodium sulfate. The solvent was removed and the resulting residue was purified on a silica gel column chromatography (hexane: ethyl acetate = 5: 1) to obtain 4,6-dichloro-2-(morpholine-4-yl)pyrimidine (985mg, 28percent). MS(EI)m/z:233(M+) HRMS(EI): Calcd for C8H9Cl2N3O: 233.0123; found:233.0152
Reference: [1] Patent: EP1473295, 2004, A1, . Location in patent: Page 20
  • 3
  • [ 110-91-8 ]
  • [ 3764-01-0 ]
  • [ 10397-13-4 ]
YieldReaction ConditionsOperation in experiment
33% at 165℃; for 0.5 h; To a solution of 2,4,6-trichloropyrimidine (5.0 mL, 42.6 mmol) in mesitylen (80 mL) at 165° C. was added dropwise a solution of morpholine (4.83 mL, 55.4 mmol) in mesitylen (20 mL) and the suspension was stirred at 165° C. for 30 min.
The reaction mixture was treated with H2O, EtOAc and NaHCO3.
The organic layer was washed with H2O and brine, dried (Na2SO4), filtered and concentrated.
The residue was purified by flash chromatography (hexane/EtOAc, 100:0→7:3).
The residue was triturated in hexane and filtered to afford the title compound (3.36 g, 33percent).
tR: 1.11 min (LC-MS 1); ESI-MS: 234.2 [M+H]+ (LC-MS 1).
1.4 g With triethylamine In dichloromethane at 5 - 20℃; for 2 h; 4-(4,6-dichloropyrimidin-2-yl)morpholine
The solution of compound 1-a (5.0 g, 27.5 mmol) and triethylamine (3.0 g, 30 mmol) in 25 ml of dichloromethane was added dropwise to a solution of morpholine (2.4 g, 27.5 mmol) in 5 ml of dichloromethane at 5 to 15°C and stirred at room temperature for 2 hours.
The reaction was completed and the mixture was extracted with dichloromethane.
The combined organic phases were separated and concentrated under reduced pressure to give the crude product which was purified by Combi-flash column chromatography to give compound 1-b (1.4 g). Purity: 95percent.
Spectrum data: MS m/z(ESI): 234[M+H]+.
Reference: [1] Patent: US2013/225574, 2013, A1, . Location in patent: Paragraph 0502; 0503
[2] Patent: WO2006/65872, 2006, A1, . Location in patent: Page/Page column 48
[3] Patent: WO2006/71538, 2006, A2, . Location in patent: Page/Page column 43
[4] Patent: WO2008/32033, 2008, A1, . Location in patent: Page/Page column 89
[5] Patent: WO2008/32036, 2008, A1, . Location in patent: Page/Page column 102
[6] Patent: WO2008/32089, 2008, A1, . Location in patent: Page/Page column 90
[7] Patent: WO2008/32027, 2008, A1, . Location in patent: Page/Page column 90
[8] Patent: EP3235816, 2017, A1, . Location in patent: Paragraph 0112-0113
[9] Patent: WO2008/32033, 2008, A1, . Location in patent: Page/Page column 89
[10] Patent: WO2008/32089, 2008, A1, . Location in patent: Page/Page column 90
[11] Patent: WO2008/32036, 2008, A1, . Location in patent: Page/Page column 102
  • 4
  • [ 24193-00-8 ]
  • [ 10397-13-4 ]
YieldReaction ConditionsOperation in experiment
50% at 120℃; for 16 h; 0341] A mixture of 2-morpholinopyrimidine-4,6-diol (30 g, 0.15 mol) and POCl3(150 mL, 1.61 mol) was heated at 1200C for 16 h, then cooled to RT. Excess POCl3 was removed to give a semi-solid. The solid was gradually transferred to a stirring solution of water (700 mL) and EtOH (100 mL) occasionally cooled with water. White solid formed and was subsequently filtered, washed with water, 10percent EtOH in water, and dried over P2O5 to give 4,6-dichloro-2-morpholinopyrimidine (17.82 g, 50percent). LC/MS (m/z): 233.9 (MH+), Rt 2.95 minutes.
Reference: [1] Patent: WO2007/84786, 2007, A1, . Location in patent: Page/Page column 119-120
[2] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 1, p. 34 - 38
[3] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 10, p. 774 - 779
[4] Patent: WO2009/66084, 2009, A1, . Location in patent: Page/Page column 62
  • 5
  • [ 50596-83-3 ]
  • [ 10397-13-4 ]
Reference: [1] Patent: US3984411, 1976, A,
  • 6
  • [ 17238-66-3 ]
  • [ 10397-13-4 ]
Reference: [1] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 1, p. 34 - 38
  • 7
  • [ 110-91-8 ]
  • [ 10397-13-4 ]
  • [ 10244-24-3 ]
YieldReaction ConditionsOperation in experiment
93%
Stage #1: With triethylamine In 1-methyl-pyrrolidin-2-one at 85℃; for 2.25 h; Heating / reflux
Stage #2: With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one; water; ethyl acetate
0388] To a slurry of 2-moφholino-4,6-dichloropyrimidine (prepared as inMethod 22, 2.0 g, 8.54 mmol) in NMP (14 mL), triethylamine (1.43 mL, 10.25 mmol) was added. The heterogeneous mixture was stirred for 15 minutes, then treated with morpholine (0.75 mL, 8.54 mmol). Upon refluxing at 85 0C under argon for 2 hours, the solution was cooled, then added to EtOAc (160 mL). The organic solution was washed with 25 mL of NaHCO3(sat.) (2 x), water (2 x) and brine, dried over Na2SO4, filtered and concentrated. The crude material was dissolved in 200 mL EtOAc and filtered through a SiO2 pad, further eluting with EtOAc, yielding 2.2 g (93percent) of 2,4-dimorpholino-6- chloropyrimidine as an off-white solid. LCMS (m/z): 285.0 (MH+), 1H NMR (CDCl3): δ 5.86 (s, IH), 3.71-3.76(m, 12H), 3.52-3.56(m, 4H).
93%
Stage #1: With triethylamine In 1-methyl-pyrrolidin-2-one for 0.25 h;
Stage #2: at 85℃; for 2 h; Inert atmosphere
Stage #3: With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one; ethyl acetate
To a slurry of 2-mo holino-4,6-dichloropyτimidine (prepared as in Method 22, 2.0 g, 8.54 mmol) in NMP (14 mL), triethylamine (1.43 mL, 10.25 mmol) was added. The heterogeneous mixture was stirred for 15 minutes, then treated with ηιοφιοηβ (0.75 mL, 8.54 mmol). Upon refluxing at 85 °C under argon for 2 hours, the solution was cooled, then added to EtOAc (160 mL). The organic solution was washed with 25 mL of NaHC03(sat.) (2 x), water (2 x) and brine, dried over Na2S04, filtered and concentrated. The crude material was dissolved in 200 mL EtOAc and filtered through a S1O2 pad, further eluting with EtOAc, yielding 2.2 g (93percent) of 2,4-dimoφholino-6-chloropyrimidine as an off-white solid. LCMS im/z): 285.0 (MH ), ^ NMR CDCls): δ 5.86 (s, 1H), 3.71 -3.76(m, 12H), 3.52-3.56(m, 4H).
Reference: [1] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 10, p. 774 - 779
[2] Patent: WO2007/84786, 2007, A1, . Location in patent: Page/Page column 139
[3] Patent: WO2012/109423, 2012, A1, . Location in patent: Page/Page column 28
Recommend Products
Same Skeleton Products
Historical Records

Pharmaceutical Intermediates of
[ 10397-13-4 ]

Buparlisib Intermediates

Chemical Structure| 106447-97-6

[ 106447-97-6 ]

2-Amino-4-(trifluoromethyl)pyridine

Chemical Structure| 73183-34-3

[ 73183-34-3 ]

4,4,4',4',5,5,5',5'-Octamethyl-2,2'-bi(1,3,2-dioxaborolane)

Chemical Structure| 105-53-3

[ 105-53-3 ]

Diethyl malonate

Chemical Structure| 10244-24-3

[ 10244-24-3 ]

4,4'-(6-Chloropyrimidine-2,4-diyl)dimorpholine

Chemical Structure| 944401-56-3

[ 944401-56-3 ]

5-Bromo-4-(trifluoromethyl)pyridin-2-amine

Related Functional Groups of
[ 10397-13-4 ]

Chlorides

Chemical Structure| 10397-15-6

[ 10397-15-6 ]

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

Similarity: 0.77

Chemical Structure| 10244-24-3

[ 10244-24-3 ]

4,4'-(6-Chloropyrimidine-2,4-diyl)dimorpholine

Similarity: 0.77

Chemical Structure| 23631-02-9

[ 23631-02-9 ]

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

Similarity: 0.67

Chemical Structure| 57473-32-2

[ 57473-32-2 ]

5,7-Dichloroimidazo[1,2-a]pyrimidine

Similarity: 0.65

Chemical Structure| 22404-46-2

[ 22404-46-2 ]

4-Chloro-N-methylpyrimidin-2-amine

Similarity: 0.63

Related Parent Nucleus of
[ 10397-13-4 ]

Morpholines

Chemical Structure| 10244-24-3

[ 10244-24-3 ]

4,4'-(6-Chloropyrimidine-2,4-diyl)dimorpholine

Similarity: 0.77

Chemical Structure| 57356-66-8

[ 57356-66-8 ]

4-(Pyrimidin-2-yl)morpholine

Similarity: 0.73

Chemical Structure| 663194-10-3

[ 663194-10-3 ]

4-(4-Bromopyrimidin-2-yl)morpholine

Similarity: 0.67

Chemical Structure| 19810-79-8

[ 19810-79-8 ]

2-Morpholinopyrimidin-4-ol

Similarity: 0.66

Chemical Structure| 861031-56-3

[ 861031-56-3 ]

2-Amino-4-morpholin-4-yl-pyrimidine

Similarity: 0.61

Pyrimidines

Chemical Structure| 10397-15-6

[ 10397-15-6 ]

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

Similarity: 0.77

Chemical Structure| 10244-24-3

[ 10244-24-3 ]

4,4'-(6-Chloropyrimidine-2,4-diyl)dimorpholine

Similarity: 0.77

Chemical Structure| 57356-66-8

[ 57356-66-8 ]

4-(Pyrimidin-2-yl)morpholine

Similarity: 0.73

Chemical Structure| 23631-02-9

[ 23631-02-9 ]

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

Similarity: 0.67

Chemical Structure| 663194-10-3

[ 663194-10-3 ]

4-(4-Bromopyrimidin-2-yl)morpholine

Similarity: 0.67