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Product Details of [ 56-05-3 ]

CAS No. :56-05-3 MDL No. :MFCD00006090
Formula : C4H3Cl2N3 Boiling Point : -
Linear Structure Formula :- InChI Key :JPZOAVGMSDSWSW-UHFFFAOYSA-N
M.W :163.99 Pubchem ID :65522
Synonyms :

Calculated chemistry of [ 56-05-3 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 36.46
TPSA : 51.8 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) : -6.04 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.42
Log Po/w (XLOGP3) : 1.78
Log Po/w (WLOGP) : 1.37
Log Po/w (MLOGP) : 0.6
Log Po/w (SILICOS-IT) : 1.64
Consensus Log Po/w : 1.36

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.47
Solubility : 0.554 mg/ml ; 0.00338 mol/l
Class : Soluble
Log S (Ali) : -2.49
Solubility : 0.535 mg/ml ; 0.00327 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.52
Solubility : 0.5 mg/ml ; 0.00305 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.62

Safety of [ 56-05-3 ]

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 [ 56-05-3 ]

* 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 [ 56-05-3 ]
  • Downstream synthetic route of [ 56-05-3 ]

[ 56-05-3 ] Synthesis Path-Upstream   1~31

  • 1
  • [ 56-05-3 ]
  • [ 74-89-5 ]
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YieldReaction ConditionsOperation in experiment
91% With N-ethyl-N,N-diisopropylamine In methanol; butan-1-ol at 95℃; Intermediate 20 -chloro-6-(2,3-dichlorophenyl)pyrimidin-2-amine. A mixture of 4,6-dichloropyrimidin-2-amine (3.28 g, 20.0 mmol), methanamine (12.0 mL, 24.0 mmol; as a 2 M solution in methanol) and Hunig's base in n- butanol (20 mL) was heated at 95°C overnight. The mixture was concentrated and the crude was taken up in EtOAc (300 mL) and washed with water (3 x 150 mL). The organic layer was dried over MgS04, filtered and concentrated to give the desired product as a buff solid (2.90 g, 91 percent). LCMS [M+H]+ 159.
90.6% at 80℃; for 6 h; Sealed tube 2-Amino-4,6-dichloropyrimidine (1.0 g, 6.1 mmol) was dissolved in 15 mL of methylamine solution.The tube was sealed at 80 ° C for 6 h.Dry the solvent,Ethyl acetate dissolved,Column chromatography purification [P: E = 4: 1 (V: V)],Obtained white solid 0.87g,The yield was 90.6percent.
85% With potassium carbonate In ethanol for 18 h; Heating / reflux 2-Amino-4-chloro-6-methylayninopyrimidine (NU6042) (for Use as an Intermediate Compound)
A mixture of 2-amino-4,6-dichloropyrimidine (1 g, 6.1 mmol), methylamine (0.8 ml), potassium carbonate (0.5 g, 3.62 mmol) and anhydrous ethanol (15 ml) were heated under reflux, under nitrogen, for 18 h.
The reaction mixture was cooled to room temperature, filtered, and the filtrate was concentrated to a volume of approximately 2 ml, when a cream solid was obtained (0.82 g, 85percent), m.p. 152-157° C.; νmax/cm-1 3442 (NH), 2934 (CH3), 2549 (NH2); δH (200 MHz, d6-DMSO) 3.48 (3H, s, CH3), 5.84 (1H, s, C(5)H), 6.53 (2H, br s, NH2), 7.28 (1H, br s, NH); m/z (+EI) 158 (M+, 100percent), 123 (M+-Cl, 9), 94 (18).
Reference: [1] Patent: WO2015/187089, 2015, A1, . Location in patent: Page/Page column 70
[2] Patent: CN108191774, 2018, A, . Location in patent: Paragraph 0203; 0204; 0205
[3] Patent: US6677345, 2004, B1, . Location in patent: Page/Page column 12
[4] Patent: WO2010/120854, 2010, A1, . Location in patent: Page/Page column 87
[5] Journal of Medicinal Chemistry, 2011, vol. 54, # 6, p. 1871 - 1895
[6] Patent: US2016/159750, 2016, A1, . Location in patent: Paragraph 0404-0406
[7] Patent: CN105732516, 2016, A, . Location in patent: Paragraph 0017; 0018
[8] DRP/DRBP Org.Chem.,
[9] Patent: US2585906, 1949, ,
  • 2
  • [ 56-05-3 ]
  • [ 124-40-3 ]
  • [ 1007-11-0 ]
YieldReaction ConditionsOperation in experiment
94% With N-ethyl-N,N-diisopropylamine In acetonitrile at 50℃; for 1.5 h; Intermediate 32; δ-Chloro-ΛΛΛ^-dimethyl^^-pyrimidinediamine; To a solution of 4,6-dichloropyrimidinamine (2.0 g, 12.2 mmol) in acetonitrile were added Hunig's base (2.34 mL, 13.4 mmol) and dimethylamine (6.7 mL, 13.4 mmol), and the reaction mixture was stirred for 1.5 hours at 50 0C. The mixture was poured onto CH2CI2 and water. The organic layer was separated, washed with brine, and concentrated to afford the title compound (2.2 g, 94percent) as an off-white solid. LC-MS (ES) m/z = 173, 175 [M+H]+.
Reference: [1] Patent: WO2010/59658, 2010, A1, . Location in patent: Page/Page column 121
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 3011
[3] Journal of the Chemical Society, 1957, p. 2151[4] Journal of the Chemical Society, 1952, p. 1532
[5] Organic Magnetic Resonance, 1982, vol. 20, # 4, p. 274 - 275
[6] Journal of Medicinal Chemistry, 2011, vol. 54, # 6, p. 1871 - 1895
  • 3
  • [ 56-05-3 ]
  • [ 506-59-2 ]
  • [ 1007-11-0 ]
Reference: [1] Patent: WO2010/120854, 2010, A1, . Location in patent: Page/Page column 90
  • 4
  • [ 56-05-3 ]
  • [ 3764-01-0 ]
Reference: [1] Organic Process Research and Development, 2017, vol. 21, # 1, p. 44 - 51
  • 5
  • [ 3764-01-0 ]
  • [ 10132-07-7 ]
  • [ 56-05-3 ]
Reference: [1] Chemische Berichte, 1903, vol. 36, p. 2234
[2] Chemische Berichte, 1901, vol. 34, p. 3363
[3] Chemische Berichte, 1903, vol. 36, p. 2234
[4] Chemische Berichte, 1901, vol. 34, p. 3363
[5] Chemische Berichte, 1903, vol. 36, p. 2234
[6] Chemische Berichte, 1901, vol. 34, p. 3363
[7] Journal of Heterocyclic Chemistry, 1999, vol. 36, # 5, p. 1259 - 1261
  • 6
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  • [ 10132-07-7 ]
  • [ 56-05-3 ]
Reference: [1] Chemische Berichte, 1903, vol. 36, p. 2227
[2] Chemische Berichte, 1901, vol. 34, p. 3363
[3] Chemische Berichte, 1903, vol. 36, p. 2227
[4] Chemische Berichte, 1901, vol. 34, p. 3363
  • 7
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  • [ 56-05-3 ]
YieldReaction ConditionsOperation in experiment
98.8% at 40 - 90℃; for 2 h; In a four-necked flask equipped with a reflux condenser, warm up and stir. 510 g of 2-amino-4,6-dihydroxypyrimidine (content 98percent, 4 mol) was added using a constant pressure dropping funnel. And 1428 g of phosphorus oxychloride (content 99percent). The temperature was raised to 40 to 45 ° C and 810 g of triethylamine (content 99percent) was added dropwise. After the addition was completed, the temperature was raised to 85 to 90 ° C and kept for 2 hours. HPLC (high performance liquid phase) analysis of 2-amino-4,6-dihydroxypyrimidine was less than 1percent, and the reaction was completed. Add 3000g of toluene, cool down to 0 ~ 10 ° C, add 3000g of ice water mixture, hydrolyze at low temperature, and raise to room temperature. Layered. The aqueous layer was extracted twice with 400 g of toluene, and the organic phases were combined, washed with aqueous sodium carbonate and washed with water to neutral. The organic phase was concentrated and 1800 g of toluene was recovered. 2668g of a high concentration toluene solution was obtained, and the purity by HPLC was 96.8percent. The content was 22.58percent (external standard method), and the crude product yield was 92percent.
75% With trichlorophosphate In <i>N</i>,<i>N</i>-dimethyl-aniline at 60℃; Vacuum-dried 2-amino-4,6-dihydroxypyrimidine(15 mmol) was treated with phosphorous oxychloride (45 mmol), and the mixtureheated to 60 °C for 4-5 hours. While maintaining this temperature, N,N-dimethylaniline (22 mmol) was addedover a period of one hour. The reaction mixture was stirred for an additionalhour, then cooled to 0 °C, and quenched with water. The resultingprecipitates were filtered and washed with water and dried under vacuum to getyellowish white 2-amino-4,6-dichloropyrimidine. Crystallization was carried outfrom ethanol.Yield: 75percent;solid, m.p. 217-219 °C; Rf: 0.42 (ethyl acetate/hexanes, 5:5);1H-NMR (300 MHz, DMSO-d6): δ7.58 (s, 2H, NH2),6.85 (s, 1H, H-5); EI MS: m/z(rel. abund. percent) 163 (M+, 77.6), 165 (M+ + 2,51.6), 145 (22.7), 128 (100), 92 (22.6); HR-EIMS calcd for C4H3N3Cl2:162.9704; observed 162.9703; Anal. calcd for C4H3Cl2N3:C, 29.30; H, 1.84; N, 25.62; Found: C, 29.51; H, 1.94; N, 26.75.
Reference: [1] Patent: CN108395409, 2018, A, . Location in patent: Paragraph 0046-0047; 0050
[2] Organic Letters, 2009, vol. 11, # 1, p. 61 - 64
[3] Chemical Communications, 2017, vol. 53, # 18, p. 2689 - 2692
[4] Organic and Biomolecular Chemistry, 2017, vol. 15, # 47, p. 10087 - 10094
[5] Tetrahedron Letters, 2015, vol. 56, # 10, p. 1179 - 1182
[6] Patent: US2018/155298, 2018, A1, . Location in patent: Paragraph 1106; 1107
  • 8
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  • [ 56-05-3 ]
Reference: [1] Chemische Berichte, 1903, vol. 36, p. 2234
[2] Chemische Berichte, 1901, vol. 34, p. 3363
[3] Chemische Berichte, 1903, vol. 36, p. 2234
[4] Chemische Berichte, 1901, vol. 34, p. 3363
[5] Chemische Berichte, 1903, vol. 36, p. 2234
[6] Chemische Berichte, 1901, vol. 34, p. 3363
[7] Journal of Heterocyclic Chemistry, 1999, vol. 36, # 5, p. 1259 - 1261
  • 9
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  • [ 56-05-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2429 - 2439
  • 10
  • [ 4425-67-6 ]
  • [ 56-05-3 ]
  • [ 51501-53-2 ]
Reference: [1] Journal of the American Chemical Society, 1950, vol. 72, p. 4271[2] Journal of the American Chemical Society, 1951, vol. 73, p. 3862
  • 11
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Reference: [1] Journal of Heterocyclic Chemistry, 1999, vol. 36, # 5, p. 1259 - 1261
  • 12
  • [ 56-09-7 ]
  • [ 56-05-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 23, p. 6610 - 6614
  • 13
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  • [ 7664-41-7 ]
  • [ 10132-07-7 ]
  • [ 56-05-3 ]
Reference: [1] Chemische Berichte, 1903, vol. 36, p. 2227
[2] Chemische Berichte, 1901, vol. 34, p. 3363
[3] Chemische Berichte, 1903, vol. 36, p. 2227
[4] Chemische Berichte, 1901, vol. 34, p. 3363
  • 14
  • [ 56-05-3 ]
  • [ 156-83-2 ]
Reference: [1] Chemische Berichte, 1903, vol. 36, p. 2234
[2] Chemische Berichte, 1901, vol. 34, p. 3363
  • 15
  • [ 56-05-3 ]
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  • [ 156-83-2 ]
Reference: [1] Chemische Berichte, 1903, vol. 36, p. 2234
[2] Chemische Berichte, 1901, vol. 34, p. 3363
  • 16
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  • [ 1194-21-4 ]
YieldReaction ConditionsOperation in experiment
86% With sodium hydroxide In water for 5 h; Reflux To a solution of 4,6-dichloropyrimidin-2-amine (21.2 g, 129.27 mmol) in 200 mL of IN NaOH was added NaOH (4 g, 100.00 mmol) in several batches. The resulting solution was refluxed for 5 hours. The reaction mixture was cooled in a bath of H2O/ice. Adjustment of the pH to 5-6 was accomplished by the addition of CH3COOH. A filtration was performed and the filter cake was collected. The solid was washed with water and dried under an oven with reduced pressure. This resulted in 17 g (86percent) of 2-amino-6-chloropyrirnidin-4(3H)-one as a white solid.
Reference: [1] Chemistry (Weinheim an der Bergstrasse, Germany), 2002, vol. 8, # 1, p. 293 - 301
[2] Organic Letters, 2009, vol. 11, # 1, p. 61 - 64
[3] Patent: WO2009/139834, 2009, A1, . Location in patent: Page/Page column 93
[4] Journal of the Chemical Society, 1951, p. 3,6
[5] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 8, p. 1081 - 1083
[6] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 23, p. 6610 - 6614
[7] Patent: WO2004/56831, 2004, A1, . Location in patent: Page 74-75
  • 17
  • [ 67-56-1 ]
  • [ 56-05-3 ]
  • [ 5734-64-5 ]
YieldReaction ConditionsOperation in experiment
84%
Stage #1: With sodium hydride In tetrahydrofuran for 0.25 h; Inert atmosphere
Stage #2: for 15 h; Inert atmosphere
General procedure: Intermediates Id–f were prepared by a method similar to that for intermediates Ia–c. A solution ofNaH (5.8 mmol) in dry THF (12 mL) was cooled to 0 °C under N2, then a substituted alcohol (6.1 mmol)was added dropwise. The mixture was stirred for 15 min while maintaining the temperature at 0 °C.Next, 2-amino-4-chloro-6- substituted-pyrimidine (5.8 mmol) was added to the solution. The reactionwas continued at 62 °C for 15 h. Then the mixture was cooled to ambient temperature, and quenchedwith 1 mL of 1 M hydrochloric acid solution. The mixture was diluted with EtOAc (20 mL), washedtwice with a saturated NaHCO3 solution (20 mL) and brine (20 mL), dried with anhydrous Na2SO4and evaporated in vacuo. Finally, the residue was purified by silica gel column chromatography(EtOAc/petroleum ether) to afford compounds Id–f. 4-Chloro-6-methoxypyrimidin-2-amine (Id). White solid, mp 165–167 °C, yield = 84percent. 1H-NMR (CDCl3) δ 6.04 (s, 1H, ArH), 5.35–5.14 (m, 2H, NH2), 3.81 (s, 3H, OCH3).
Reference: [1] Patent: WO2004/37795, 2004, A1, . Location in patent: Page/Page column 8
[2] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 10, p. 774 - 779
[3] Molecules, 2018, vol. 23, # 9,
[4] Nippon Kagaku Zasshi, 1953, vol. 74, p. 624[5] Chem.Abstr., 1954, p. 13693
[6] Patent: US4645530, 1987, A,
[7] Patent: US4547215, 1985, A,
  • 18
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  • [ 5734-64-5 ]
YieldReaction ConditionsOperation in experiment
90% for 20 h; Heating / reflux To a solution of 4,6-dichloro-2-amino pyrimidine (5.0 g, 30.5 mmol) in MeOH (100 mL) was added 25percent sodium methoxide (6.59 g, 30.5 mmol). The solution was refluxed for 20 hours, at which time the methanol was removed in vacuo. The residue was dissolved in EtOAc (350 mL), washed with H2O (100 mL) and with NaCl(sat.) (100 mL), dried over Na2SO4, filtered and concentrated yielding 4.4 g (90percent) of 4-chloro- 6-methoxypyrimidine-2-ylamine.
88.7% for 2 h; Inert atmosphere; Reflux In 500mL eggplant-shaped flask,2-Amino-4,6-dichloropyrimidine (50.0 g, 304.9 mmol)Dissolved in tetrahydrofuran (200 mL),Sodium methoxide (32.9 g, 609.8 mmol) was added under N2 protection,Reflux 2h.The reaction was completed, cooled, the reaction liquid into the water, suction filtration, the filter cake was beaten with methanol (80mL × 1)The filtrate was filtered to obtain 2-amino-4-chloro-6-methoxypyrimidine 43.2g, the yield was 88.7percent.
Reference: [1] Patent: WO2004/37795, 2004, A1, . Location in patent: Page/Page column 6-7
[2] Patent: WO2004/37795, 2004, A1, . Location in patent: Page/Page column 8
[3] Patent: WO2008/98058, 2008, A1, . Location in patent: Page/Page column 65
[4] Patent: CN106966992, 2017, A, . Location in patent: Paragraph 0005; 0027; 0028
[5] Chemische Berichte, 1903, vol. 36, p. 3383
[6] Chemische Berichte, 1903, vol. 36, p. 3383
[7] Pesticide Science, 1996, vol. 47, # 2, p. 103 - 114
[8] Patent: US2016/159750, 2016, A1, . Location in patent: Paragraph 0400
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  • [ 124-41-4 ]
  • [ 5734-64-5 ]
YieldReaction ConditionsOperation in experiment
90% for 20 h; Heating / reflux 0262] To a solution of 4,6-dichloro-2-amino pyrimidine (5.0 g, 30.5 mmol) in methanol (100 mL) was added 25percent sodium methoxide (6.59 g, 30.5 mmol). The solution was refluxed for 20 hours, at which time the methanol was removed in vacuo. The residue was dissolved in EtOAc (350 mL), washed with H2O (100 mL) and with NaCl(Sat.) (100 mL), dried over Na2SO4, filtered and concentrated yielding 4.4 g (90percent) of 4-chloro- 6-methoxypyrimidine-2-ylamine.
Reference: [1] Patent: WO2004/37795, 2004, A1, . Location in patent: Page/Page column 9
[2] Patent: WO2007/84786, 2007, A1, . Location in patent: Page/Page column 98-99
[3] Journal of the Chemical Society, 1946, p. 81,84
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  • [ 64-17-5 ]
  • [ 89784-02-1 ]
Reference: [1] Nippon Kagaku Zasshi, 1953, vol. 74, p. 624[2] Chem.Abstr., 1954, p. 13693
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  • [ 141-52-6 ]
  • [ 89784-02-1 ]
Reference: [1] Journal of the Chemical Society, 1946, p. 81,84
  • 22
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  • [ 71-43-2 ]
  • [ 3740-92-9 ]
Reference: [1] European Journal of Medicinal Chemistry, 2005, vol. 40, # 9, p. 862 - 874
  • 23
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  • [ 51501-53-2 ]
YieldReaction ConditionsOperation in experiment
86.8% With N-chloro-succinimide In chloroform for 2 h; Reflux A suspension of 2-amino-4,6-dichloropyrimidine (2.0 g, 12.20 mmol) in chloroform (30 mL) was prepared and N-chlorosuccinimide (1.71 g, 12.81 mmol) was added portionwise. The reaction mixture was refluxed for 2 h. The reaction mixture was cooled to room temperature, diluted with a saturated solution of NaHCCb then extracted with DCM and ethyl acetate. A precipitate formed which was removed by filtration. The combined organic extracts were dried and concentrated under reduced pressure. The crude residue was purified by column chromatography, eluting with 0 - 40percent EtOAc in cyclohexane. The appropriate fractions were combined and concentrated to give the title compound (2.1 g, 86.8percent yield). LCMS: RT 4.03 mm, MI 199.8, Method (4LCMS1)
86.8% With N-chloro-succinimide In chloroform for 2 h; Reflux [00232] A suspension of 2-amino-4,6-dichloropyrimidine (2.0 g, 12.20 mmol) in chloroform (30 mL) was prepared and N-chlorosuccinimide (1 .71 g, 12.81 mmol) was added portionwise. The reaction mixture was refluxed for 2 h. The reaction mixture was cooled to room temperature, diluted with a saturated solution of NaHC03 then extracted with DCM and ethyl acetate. A precipitate formed which was removed by filtration. The combined organic extracts were dried and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel, eluting with 0 - 40percent EtOAc in cyclohexane. The appropriate fractions were combined and concentrated to give the title compound (2.1 g, 86.8percent yield). LCMS: RT 4.03 min, Ml 199.8, Method (4LCMS1 )
Reference: [1] Patent: WO2018/55402, 2018, A1, . Location in patent: Page/Page column 224-225
[2] Patent: WO2018/87527, 2018, A1, . Location in patent: Paragraph 00231-00232
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Reference: [1] Journal of the American Chemical Society, 1950, vol. 72, p. 4271[2] Journal of the American Chemical Society, 1951, vol. 73, p. 3862
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YieldReaction ConditionsOperation in experiment
88% With bromine; sodium acetate In water; acetic acid Example 52
5-Bromo-6-(5-chloro-2-methoxy-phenyl)-N*4*-(1H-indazol-6-yl)-pyrimidine-2,4-diamine
To a stirred mixture of 4,6-dichloro-pyrimidin-2-yl-amine (2.46 g, 15.0 mmol) and sodium acetate (6.15 g, 75.0 mmol) in acetic acid (150 ml) was added bromine (3.24 g, 20.25 mmol) dropwise.
The mixture was then stirred at 60° C. for 2 hours.
Volatiles were evaporated under reduced pressure.
The residue was stirred with water (500 ml) for 1 hour, filtered, and dried under reduced pressure to provide 2-amino-4,6-dichloro-5-bromo-pyrimidine (3.2 g, 88percent yield) as a white solid.
83.7% With bromine; sodium carbonate In methanol; water at 20 - 30℃; for 42.5 h; Bromine (0.85 mL, 0.0166 mole) was added dropwise over 20 minutes to a stirred suspension of 2-amino-4,6-dichloropyrimidine (CAS#56-05-3, 1.70 g, 0.01037 mole) and sodium carbonate (1.00 g, 0.01244 mole) in 1:1 methanol/water (30 mL) at ambient temperature.
Ten minutes after the addition was complete, more sodium carbonate (0.78 g, 0.0093 mole) was added to the reaction mixture.
The reaction mixture was stirred at ambient temperature for 42 hours, then it was diluted with aqueous sodium bicarbonate to provide 5-bromo-4,6-dichloropyrimidin-2-amine as a precipitate that was collected by filtration and rinsed with water.
The vacuum-dried solid weighed 2.11 g (83.7percent yield).
1H NMR (300 MHz, d6-DMSO) δ ppm 7.67 (s, 1H), 7.70 (s, 1H). MS (DCl-NH3) m/z=241 (M+H)+, m/z=258 (M+NH4)+.
Reference: [1] Patent: US2004/204386, 2004, A1,
[2] Patent: US2010/331294, 2010, A1, . Location in patent: Page/Page column 18
[3] Yakugaku Zasshi, 1942, vol. 62, p. 315,333; dtsch. Ref. S. 95, 106[4] Chem.Abstr., 1951, p. 5150
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  • [ 3824-45-1 ]
Reference: [1] Tetrahedron, 1996, vol. 52, # 1, p. 23 - 36
  • 27
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  • [ 675-11-6 ]
Reference: [1] Chemistry Letters, 1993, # 3, p. 509 - 512
  • 28
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  • [ 56-09-7 ]
  • [ 5604-46-6 ]
YieldReaction ConditionsOperation in experiment
81.3% at 5 - 20℃; for 24.5 h; Reflux DMF (2.4 mL, 31.5 mmol) was slowly added dropwise to phosphorus oxychloride (7.5 mL, 81.9 mmol) at 5-10 °C, followed by the slow addition of 2-amino-4,6-dihydroxypyrimidine (2 g, 15.74 mmol), stirred at rt for 30min, refluxed for 24h, cooled toroom temperature, the reaction solution was slowly poured into 100mL of ice water, stirred for 1h after standing overnight, filtered off with suction, washed with ice water and ethyl acetate werewash filter cake Recrystallization gave 2.44 g of a pale yellow solid, yield 81.3percent
Reference: [1] Patent: CN108371662, 2018, A, . Location in patent: Paragraph 0050; 0113; 0114; 0115; 0116
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  • [ 36314-97-3 ]
YieldReaction ConditionsOperation in experiment
64% With potassium carbonate In acetonitrile at 90℃; for 4 h; Example 2 Preparation of Compound 2 <n="41"/>Step A - Synthesis of Compound 2b; To compound 2a (2.Og, 12.2mmol) was added CH3CN (4OmL), K2CO3 (2M solution, 6.1 mL, 12.2mmol), Pd(PPh3)4 (0.35g, 0.31mmol), and PhB(OH)2 (0.74g, 6.1mmol). The solution was stirred and heated to 9O0C for 4h. Allowed to cool, transferred to sep. funnel, added CH2CI2 (5OmL), added H2O (5OmL), mixed, separated, extracted aqueous layer with CH2CI2, combined organic layers, dried (MgSO4), filtered, and concentrated. Purified using preparative thin layer chromatography (100percent CHzCI2) to yield compound 2b (0.8g, 64percent).
60% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 95℃; for 12 h; Sealed tube Intermediate 6 -chloro-6-phenylpyrimidin-2-amine. A mixture of 2-amino-4,6-dichloropyrimidine (3 g, 18.29 mmol, 1 equiv.), phenylboronic acid (2.45 g, 20.12 mmol, 1.1 equiv.), K2C03 (5.06 g, 36.6 mmol, 2 equiv.) and Pd(PPh3)4 (700 mg, 0.6 mmol, 0.03 equiv.) in 1 ,4-dioxane (15 ml_) and water (1 ml_) was heated in a sealed tube at 95°C for 12 h. The mixture was run through a plug of silica using EtOAc as eluent, concentrated and purified by column chromatography (1 :4 EtOAc/pentane) to give the desired product as a white solid (2.2 g, 60 percent). LCMS [M+H]+ 206; 1 H NMR (400 MHz, CDCI3) 5 8.27 - 8.20 (2H, m), 8.16 - 8.05 (3H, m), 7.19 (2H, s), 6.76 (1 H, s).
Reference: [1] Patent: WO2009/111449, 2009, A1, . Location in patent: Page/Page column 38-39
[2] Patent: WO2015/187089, 2015, A1, . Location in patent: Page/Page column 65
[3] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 9, p. 2303 - 2308
[4] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 16, p. 3670 - 3674
[5] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 8, p. 2497 - 2501
  • 30
  • [ 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
  • 31
  • [ 56-05-3 ]
  • [ 1612184-10-7 ]
YieldReaction ConditionsOperation in experiment
47% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 90℃; for 2 h; Sealed tube A stirred mixture of 2-amino-4,6-dichloropyrimidine (0.50 g, 3.1 mmol), 3-chloro- 2-methylphenylboronic acid (0.57 g, 3.4 mmol), Na2003 (1.0 g, 9.8 mmol), palladium tetrakis(triphenylphosphine)palladium (0) (0.088 g, 0.076 mmol),dioxane (22 mL) and water (8 mL) were heated in a sealed tube at 90 00 for 2 hours. The solvents were removed and the resulting solid was dissolved in EtOAc (20 mL) and washed with water. The organic phase was dried over MgSO4 and concentrated. The crude material was purified by flash chromatography (1:4 EtOAc/petroleum ether) to give the desired product as a white solid (0.36g, 47percent).LCMS [M+H] 254; 1H NMR (400 MHz, DMSO-d6) ö ppm 7.52 - 7.56 (1 H, dd, J1 = 6.5 Hz, J2 = 2.5 Hz) 7.30 - 7.33 (2 H, m) 7.26 (2 H, s) 6.79 (1 H, s) 2.32 (3 H,s).
47% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 90℃; for 2 h; Sealed tube Intermediate 24 4-chloro-6-(3-chloro-2-methylphenyl)pyrimidin-2-amine. A stirred mixture of 2-amino-4,6-dichloropyrimidine (0.50 g, 3.1 mmol), 3-chloro- 2-methylphenylboronic acid (0.57 g, 3.4 mmol), Na2C03 (1.0 g, 9.8 mmol), palladium tetrakis(triphenylphosphine)palladium (0) (88 mg, 0.076 mmol), dioxane (22 mL) and water (8 mL) were heated in a sealed tube at 90°C for 2 hours. The solvents were removed in vacuo and the remaining solid was added EtOAc (20 mL) and washed with water. The organic phase was dried over MgS04 and removed in vacuo. The crude material was purified by flash chromatography (1 :4 EtOAc/petroleum ether) to give the desired product as a white solid (365 mg, 47percent). LCMS [M+H]+ 254; 1 H NMR (400 MHz, DMSO-d6) δ ppm 7.52 - 7.56 (1 H, dd, J = 6.5 Hz, J2 = 2.5 Hz) 7.30 - 7.33 (2 H, m) 7.26 (2 H, s) 6.79 (1 H, s) 2.32 (3 H, s).
Reference: [1] Patent: WO2015/187088, 2015, A1, . Location in patent: Page/Page column 41; 42
[2] Patent: WO2015/187089, 2015, A1, . Location in patent: Page/Page column 71; 72
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