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Chemical Structure| 49845-33-2
Chemical Structure| 49845-33-2
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Product Details of [ 49845-33-2 ]

CAS No. :49845-33-2 MDL No. :MFCD00127867
Formula : C4HCl2N3O2 Boiling Point : -
Linear Structure Formula :- InChI Key :INUSQTPGSHFGHM-UHFFFAOYSA-N
M.W : 193.98 Pubchem ID :521266
Synonyms :

Calculated chemistry of [ 49845-33-2 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 40.87
TPSA : 71.6 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) : -6.1 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.0
Log Po/w (XLOGP3) : 1.95
Log Po/w (WLOGP) : 1.69
Log Po/w (MLOGP) : -0.29
Log Po/w (SILICOS-IT) : 0.28
Consensus Log Po/w : 0.93

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.61
Solubility : 0.477 mg/ml ; 0.00246 mol/l
Class : Soluble
Log S (Ali) : -3.08
Solubility : 0.162 mg/ml ; 0.000835 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.27
Solubility : 1.04 mg/ml ; 0.00538 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.0

Safety of [ 49845-33-2 ]

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 [ 49845-33-2 ]

* 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.

  • Upstream synthesis route of [ 49845-33-2 ]
  • Downstream synthetic route of [ 49845-33-2 ]

[ 49845-33-2 ] Synthesis Path-Upstream   1~19

  • 1
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YieldReaction ConditionsOperation in experiment
94% With trichlorophosphate In <i>N</i>,<i>N</i>-dimethyl-aniline at 110℃; for 8 h; 5-nitro-uracil (6.28 g, 0.040 mol) was mixed with phosphorus oxychloride (26 ml) and slowly added with stirringN, N-dimethylaniline (8 ml) and then heated to 110 ° C for 8 h. After the reaction, the excess phosphorus oxychloride was distilled off,And the mixture was triturated and chromatographed on silica gel and concentrated to give 6.2 g of a yellow oily liquid. (Yield: 94percent)
68% Reflux Example 1; Compounds Made by Route 1Example 1.1 7-Methoxy-3-phenyl-pyrimido[5,4-e][l,2,4]triazineStep A: 2,4-Dichloro-5-nitropyrimidineFollowing the procedure in Route 1, a mixture of 5-nitrouracil (5.0 g, 31.8 mmol), phosphoryl chloride (25.0 ml, 274 mmol) and dimethylaniline (6 ml, 47.8 mmol) was heated with occasional shaking, until the reaction commenced. When this had subsided the mixture was refluxed for 2 h, then cooled, and most of the phosphoryl chloride evaporated off under reduced pressure. The residue was poured on ice with vigorous stirring and, after 5 minutes, extracted with ether, the extract was washed with water and dried with Na2SO4. Removal of the ether and distillation of the residue gave the title compound as a pale yellow oil (4.2 g, 68percent). 1H NMR (CDCl3, 300 MHz): δ 9.16 (s, IH).
51% at 150℃; for 1.25 h; N,N-dimethylaniline (12.1 mL, 95.5 mmol) is combined with 5-nitrouracil (10.0 g, 63.7 mmol) and stirred under a N2 atmosphere. Phosphorous oxychloride (23.7 mL, 254.6 mmol) is slowly added to the stirring mixture. Upon completion of addition, the mixture is heated to 150° C. for 75 min. The reaction mixture was then poured over ice and extracted with Et2O (3.x.250 mL). The combined organics are washed with brine, dried over MgSO4 and concentrated to afford the crude product as a brown oil (6.3 g, 51percent) which was further used without purification. 1H NMR (300 MHz, CDCl3) δ 9.19 (s, 1H).
41% for 3 h; Reflux; Inert atmosphere 5-nitropyrimidine-2,4(1H,3H)-dione 5 (8.66 g, 55.1 mmol) was dissolved in freshly distilled phosphorus oxytrichloride (25.7 mL, 275.5 mmol) at room temperature. N,N-Dimethylaniline (17.4 mL, 137.8 mmol) was added dropwise to the stirred solution and the reaction was refluxed for 3 hours, or until complete. The black solution was cooled and concentrated under reduced pressure to remove excess phosphorus oxytrichloride, then poured into ice-water (82 mL). The aqueous solution was extracted with diethyl ether (3 x 110 mL), and the combined organic layers were washed with brine (160 mL), dried over anhydrous magnesium sulfate and the solvent evaporated to yield a brown oil. The crude product was purified by silica gel chromatography using ethyl acetate/hexane (1/10 v/v) as an eluent. The product was obtained as a yellow oil 5 (4.3 g, 22.5 mmol, 41percent). m.p. 29-30 °C; Rf 0.42 (1/10 v/v ethyl acetate/hexane); IR (ZnSe cell, solid) vmax: 1541 (s, NO2), 1342 (s, NO2/C-N=C), 1305 (s, NO2/C-N=C), 1203 (s, C-Cl), 1178 (s, C-Cl), 871 (s, C=C-H), 678 (s, C=C-H); 1H NMR (500 MHz, CDCl3): δ 9.16 (1H, s) ppm; 13C NMR (125 MHz, CDCl3): δ 162.74 (4-CCl), 156.62 (6-CH), 155.69 (2-CCl), 141.67 (5-CNO2) ppm; LRMS (+ GC/MS, 3.14 min) m/z: 197, 195, 193 ([M]+, 7, 39, 59percent), 160, 158 ([M - Cl]+, 25, 70percent), 137, 135 ([M - (CH2ClN)2 + H]+, 34, 53percent), 124, 122, 120 ([M – (C2HClN)3 + H]+, 11, 65, 100percent), 93 (63percent), 65, 63 (32, 78percent).
16.8 g at 130℃; for 3 h; 25 gm of 5-nitro uracil is suspended in 490 ml of phosphorous oxychloride for 10 minutes and diisopropyl ethylamine is slowly added to the suspension at room temp. The reaction suspension is refluxed at 130 oC for 3h. The solution is concentrated under reduced pressure to be a volume of 100 ml. Then the solution is added dropwise to 500 ml of ice water and stirred for 1h, and extracted with diethyl ether. The organic layer is washed with 500 ml of saturated ammonium chloride and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Column chromatography on silica gel (ethyl acetate: Hexane=1:5) affords 16.8 gm of the title compound. White solid; mp:30-32 oC; IR (KBr): 1670, 1620, 1350, 785 cm-1; 1H NMR (400 MHz, CDCl3): δ 9.25 (s, 1H, H6) ppm; m/z=195(M+).

Reference: [1] Patent: CN106432239, 2017, A, . Location in patent: Paragraph 0066; 0071; 0072
[2] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 2, p. 321 - 328
[3] Tetrahedron Letters, 2006, vol. 47, # 50, p. 8897 - 8900
[4] Patent: WO2010/83645, 2010, A1, . Location in patent: Page/Page column 27
[5] Patent: US7256196, 2007, B1, . Location in patent: Page/Page column 8; 9-10
[6] European Journal of Medicinal Chemistry, 2015, vol. 95, p. 29 - 34
[7] Chemische Berichte, 1906, vol. 39, p. 252
[8] Journal of the Chemical Society, 1951, p. 1565,1568[9] Journal of the Chemical Society, 1953, p. 1646
[10] Journal of the Chemical Society, 1951, p. 474,478[11] Journal of the Chemical Society, 1952, p. 4219,4224
[12] Journal of Medicinal Chemistry, 2004, vol. 47, # 1, p. 240 - 253
[13] Patent: US2002/52375, 2002, A1,
[14] Patent: WO2003/99809, 2003, A1, . Location in patent: Page 32
[15] Patent: WO2003/99231, 2003, A2, . Location in patent: Page 32
[16] Patent: WO2005/3099, 2005, A2, . Location in patent: Page 136-137
[17] Patent: WO2005/97162, 2005, A2, . Location in patent: Page/Page column 541; 549; 552-553
[18] Tetrahedron Letters, 2011, vol. 52, # 42, p. 5521 - 5524
[19] Patent: US2015/266828, 2015, A1, . Location in patent: Paragraph 0313
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Reference: [1] Journal of Organic Chemistry, 2015, vol. 80, # 5, p. 2676 - 2699
[2] Journal of Chemical Research, Miniprint, 1992, # 2, p. 514 - 539
[3] Patent: WO2009/155156, 2009, A1, . Location in patent: Page/Page column 77-78
  • 3
  • [ 611-08-5 ]
  • [ 10025-87-3 ]
  • [ 49845-33-2 ]
Reference: [1] Patent: US6342503, 2002, B1, . Location in patent: Example 105
  • 4
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  • [ 10025-87-3 ]
  • [ 49845-33-2 ]
Reference: [1] Patent: US6342503, 2002, B1, . Location in patent: Page column 69 - 70
  • 5
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  • [ 49845-33-2 ]
Reference: [1] Chemische Berichte, 1906, vol. 39, p. 252
  • 6
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  • [ 611-08-5 ]
Reference: [1] Synthetic Communications, 1985, vol. 15, # 3, p. 171 - 178
  • 7
  • [ 574-66-3 ]
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  • [ 611-08-5 ]
Reference: [1] Synthetic Communications, 1985, vol. 15, # 3, p. 171 - 178
  • 8
  • [ 49845-33-2 ]
  • [ 5177-27-5 ]
YieldReaction ConditionsOperation in experiment
80%
Stage #1: for 14 h;
Stage #2: With sodium carbonate In water; ethyl acetate
A heterogeneous solution of 2.4-dichloro-5-nitro-pyrimidine (1.0 eq.) and iron (6.0 eq) in acetic acid, at a concentration of 0.4 M, was stirred vigorously for 14 hours.
The mixture was then passed through a celite pad, eluting with MeOH.
Upon removal of the volatiles in vacuo, the residue was dissolved in EtOAc, washed with Na2CO3(sat.), NaCl(sat.), was dried over MgSO4, was filtered and the volatiles were removed in vacuo yielding 2,4-dichloropyrimidin-5-amine (80percent). LCMS (m/z): 157.0 (MH+); LC Rt=1.85 min.
74% at 45 - 90℃; The title compound was prepared according to the methods in Inoue, Chem. Pharm. Bull. 6:343-346, 1958. 2,4-dichloro-5-nitro-pyrimidine (20 g, 0.103 mol) in acetic acid (400 mL) was agitated using an overhead stirrer and iron powder (20 g) added. The mixture was slowly heated until approximately 45-50 °C at which point an exotherm to 85-90 °C was observed. The mixture was removed from heating and stirred for a further 60 minutes or until no starting material is observed by t.l.c.Once cooled, the reaction mixture was filtered through celite and the filtrate concentrated under vacuum. The residue was treated with a small amount of water and the solid filtered off. Whilst moist, the solid was re-crystallized from water, the solid filtered off and dried under vacuum overnight to yield the desired product(12.512 g, 0.76 mol, 74percent). 1H, 400MHz, δ (d6-DMSO): 6.07 (2H, s, NH2), 8.11 (1H, s, ArH); HPLC: 3.74 min; LRMS: m/z = 164.2 (M)
Reference: [1] Patent: US2011/195980, 2011, A1, . Location in patent: Page/Page column 17
[2] Patent: WO2011/106168, 2011, A1, . Location in patent: Page/Page column 83; 84; 101; 102
[3] Journal of the Chemical Society, 1951, p. 1565,1568[4] Journal of the Chemical Society, 1953, p. 1646
[5] Chemical and Pharmaceutical Bulletin, 1958, vol. 6, p. 352,354
[6] Patent: CN103864792, 2017, B, . Location in patent: Paragraph 0357; 0358; 0359; 0360
  • 9
  • [ 49845-33-2 ]
  • [ 1920-66-7 ]
YieldReaction ConditionsOperation in experiment
92.6% With ammonium hydroxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 1 h; To a solution of NH3.H2O (aq., 24 mL) and DIPEA (37.2 mL) in DCM (400 mL) was added dropwise a solution of compound 21-1 (30 g, 15436 mmol) in DCM at 0° C., and the reaction solution was stirred at 0° C. for 1 h, followed by filtration. The filter cake was dried to give compound 21-2 (25 g, Yield 92.6percent) as yellow solid. LCMS (ESI) m/z: 175.0 (M+1)
90.1% With ammonia; N-ethyl-N,N-diisopropylamine In dichloromethane; water at 0℃; for 1 h; Aqueous ammonia(8.0ml) and N,N-diisopropylethylamine(13.2ml) were dissolved into 150ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine(10.0g) in dichloromethane(30ml) at 0°C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for 1 hour. The precipitate was filtered off. The filter cake was recrystallized to obtain a yellow solid(8.1g) in a yield of 90.1percent. 1H NMR(400 MHz, DMSO-d6): δ 9.20(s, 1H), 9.02(s, 1H), 8.60(s, 1H)ppm.
84% With ammonium hydroxide; sodium hydroxide In tetrahydrofuran at 55℃; for 2 h; To 2,4-dichloro-5-nitropyrimidine (500 mg, 2.5 mmol) dissolved in tetrahydrofuran (10 mL), sodium hydroxide (238 mg, 2.8 mmol) and aqueous ammonia (0.3 mL) was added, and reacted for 2 hrs at 55°C. The solvent was removed under reduced pressure, and the residue was separated by flash column chromatography (dichloromethane: methanol=100:1), to obtain Compound w: 2-chloro-5-nitro-4-aminopyrimidine as a white solid (0.47 g, yield 84percent). MS(ESI)m/z: [M+H]+=175.
Reference: [1] Patent: US2017/313683, 2017, A1, . Location in patent: Paragraph 0541-0542
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 23, p. 10685 - 10699
[3] Patent: EP2578584, 2013, A1, . Location in patent: Paragraph 0071; 0072
[4] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 2, p. 321 - 328
[5] Patent: EP3284743, 2018, A1, . Location in patent: Paragraph 0135
[6] Chemische Berichte, 1906, vol. 39, p. 252
[7] Journal of Applied Chemistry, 1952, vol. 2, p. 239
[8] Journal of Medicinal Chemistry, 1992, vol. 35, # 23, p. 4455 - 4463
[9] Patent: US2005/250779, 2005, A1, . Location in patent: Page/Page column 5
[10] Patent: US2007/72862, 2007, A1, . Location in patent: Page/Page column 83-84
[11] Patent: US2012/172347, 2012, A1, . Location in patent: Page/Page column 35
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Reference: [1] Chemische Berichte, 1906, vol. 39, p. 252
  • 11
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  • [ 18620-73-0 ]
Reference: [1] Chemische Berichte, 1906, vol. 39, p. 252
[2] Journal of the Chemical Society, 1951, p. 474,478[3] Journal of the Chemical Society, 1952, p. 4219,4224
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 1, p. 240 - 253
  • 12
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Reference: [1] Chemische Berichte, 1906, vol. 39, p. 252
  • 13
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  • [ 30561-07-0 ]
Reference: [1] Patent: US5861401, 1999, A,
  • 14
  • [ 124-41-4 ]
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  • [ 30561-07-0 ]
Reference: [1] Journal of Applied Chemistry, 1957, vol. 7, p. 109,112
[2] Journal of the Chemical Society, 1957, p. 4997,5000
[3] Patent: US6342503, 2002, B1, . Location in patent: Example 105
  • 15
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  • [ 890094-38-9 ]
YieldReaction ConditionsOperation in experiment
90.4% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5 h; Isopropylamine(4.5ml) and N,N-diisopropylethylamine(13.2ml) were dissolved into 150ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine(10.0g) in dichloromethane(30ml) at 0°C. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for half an hour. Purification was conducted by a column chromatography to obtain a bright-yellow solid(10.1g) in a yield of 90.4percent. 1H NMR(400 MHz, CDCl3): δ 9.03(s, 1H), 8.24(s, 1H), 4.53(m, 1H), 1.34(d, J=6.8Hz, 6H)ppm.
81% With potassium carbonate In cyclohexane at 5 - 15℃; Step 1(1 a) (2a) (3a)Compound (1 a), 2,4-dichloro-5-nitropyrimidine, (100 g, 0.52 mol) is dissolved in 1 .0 L cyclohexane and potassium carbonate (83 g, 0.60 mol) is added. The resulting suspension is stirred at a temperature between 5 and 15°C and compound (2a), isopropylamine, (44.2 ml, 0.52 mol) is slowly added. After complete addition stirring is continued under warm up of the reaction mixture to room temperature. Water (400 mL) is added (caution: exothermic reaction). The reaction mixture is filtered. Ethyl acetate (400 mL) is added to the filtrate. The organic phase is separated, dried andevaporated.Yield: 90.9 g (81 percent of theory) of compound (3a) as a brown crystalline solid.1H-NMR confirmed the structure of compound (3a).
81% With potassium carbonate In cyclohexane at 5 - 20℃; Compound (1a), 2,4-dichloro-5-nitropyrimidine, (100 g, 0.52 mol) is dissolved in 1.0 L cyclohexane and potassium carbonate (83 g, 0.60 mol) is added. The resulting suspension is stirred at a temperature between 5 and 15° C. and compound (2a), isopropylamine, (44.2 ml, 0.52 mol) is slowly added. After complete addition stirring is continued under warm up of the reaction mixture to room temperature. Water (400 mL) is added (caution: exothermic reaction). The reaction mixture is filtered. Ethyl acetate (400 mL) is added to the filtrate. The organic phase is separated, dried and evaporated.Yield: 90.9 g (81percent of theory) of compound (3a) as a brown crystalline solid. 1H-NMR confirmed the structure of compound (3a).
Reference: [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 23, p. 10685 - 10699
[2] Patent: EP2578584, 2013, A1, . Location in patent: Paragraph 0075; 0076
[3] Patent: WO2011/101369, 2011, A1, . Location in patent: Page/Page column 48
[4] Patent: US2012/329803, 2012, A1, . Location in patent: Page/Page column 20
[5] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 16, p. 4360 - 4365
[6] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 3, p. 1427 - 1432
[7] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 1810 - 1822
[8] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 2173 - 2185
  • 16
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YieldReaction ConditionsOperation in experiment
62.8% With sodium hydrogencarbonate In cyclohexane at 80℃; for 4 h; Step 2 Methyl (2R)-2-[(2-chloro-5-nitro-pyrimidin-4-yl)-isopropyl-amino] butanoate; 2,4-Dicloro-5-nitor-pyrimidine (19.90 g, 103 mmol) was dissolved in 300 mL of cyclohexane followed by the addition of methyl (2R)-2-(isopropylamino)butanoate 22a (16.40 g, 103 mmol) and sodium bicarbonate (36.61 g, 412 mmol). The reaction solution was heated to 80°C, stirred for 4 hours and filtered. The filtrate was concentrated under reduced pressure, added with 100 mL of water and extracted with dichloromethane (100 mL.x.3). The combined organic phase was washed with saturated sodium chloride solution (100 mL), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound methyl (2R)-2-[(2-chloro-5-nitro-pyrimidin-4-yl)-isopropyl-amino]butanoate 22b (20.50 g, yield: 62.8percent) as a yellow solid.
62.8% With sodium hydrogencarbonate In cyclohexane at 80℃; for 4 h; Step 2
Methyl (2R)-2-[(2-chloro-5-nitro-pyrimidin-4-yl)-isopropyl-amino]butanoate
2,4-Dichloro-5-nitro-pyrimidine (19.90 g, 103 mmol) was dissolved in 300 mL of cyclohexane followed by the addition of methyl (2R)-2-(isopropylamino)butanoate 22a (16.40 g, 103 mmol) and sodium bicarbonate (36.61 g, 412 mmol).
The reaction solution was heated to 80° C., stirred for 4 hours and filtered.
The filtrate was concentrated under reduced pressure, added with 100 mL of water and extracted with dichloromethane (100 mL*3).
The combined organic phase was washed with saturated sodium chloride solution (100 mL), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure.
The resulting residue was purified by silica gel column chromatography to obtain the title compound methyl (2R)-2-[(2-chloro-5-nitro-pyrimidin-4-yl)-isopropyl-amino]butanoate 22b (20.50 g, yield: 62.8percent) as a yellow solid.
Reference: [1] Patent: EP2481739, 2012, A1, . Location in patent: Page/Page column 57
[2] Patent: US2012/184543, 2012, A1, . Location in patent: Page/Page column 59
[3] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2743 - 2749
[4] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 5, p. 1311 - 1315
[5] Journal of Medicinal Chemistry, 2018, vol. 61, # 17, p. 7785 - 7795
  • 17
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YieldReaction ConditionsOperation in experiment
79%
Stage #1: With sodium hydroxide In cyclohexane; water
Stage #2: With sodium hydrogencarbonate In cyclohexane for 5 h; Heating / reflux
9.3 mL of a 50percent aqueous sodium hydroxide solution is added to a stirred mixture of 33.3 g (170 mmol) 22 hydrochloride in 60 mL cyclohexane and 60 mL demineralised water. The aqueous phase is separated and the organic phase is added dropwise to a refluxed suspension of 30 g (155 mmol) 5 and 52 g (619 mmol) sodium hydrogencarbonate in 230 mL cyclohexane. The suspension is refluxed for 5 hours using a water separator to remove the formed water. 75 mL of solvent is destilled off. At 75 °C the suspension is suction filtered to remove the salts. The solvent is destilled of. The residue is dissolved in 240 mL 2-propanol and 90 mL of sovent is destilled of again. The solution is cooled slowly to 2 °C. The suspension is suction filtered and washed with cold 2-propanol. After drying in a vacuum drying oven at 50°C, 38.9 g (79percent of theory) of product 22 is obtained
Reference: [1] Patent: WO2007/90844, 2007, A1, . Location in patent: Page/Page column 12-13
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YieldReaction ConditionsOperation in experiment
79%
Stage #1: With sodium hydroxide; water In cyclohexane
Stage #2: With sodium hydrogencarbonate In cyclohexane; water for 5 h; Heating / reflux
9.3 ml. of a 50percent aqueous sodium hydroxide solution is added to a stirred mixture of 33.3 g (170 mmol) 22 hydrochloride in 60 ml. cyclohexane and 60 ml. demineralised water. The aqueous phase is separated and the organic phase is added dropwise to a refluxed suspension of 30 g (155 mmol) 5 and 52 g (619 mmol) sodium hydrogencarbonate in 230 ml. cyclohexane. The suspension is refluxed for 5 hours using a water separator to remove the formed water. 75 ml. of solvent is destilled off. At 75 0C the suspension is suction filtered to remove the salts. The solvent is destilled of. The residue is dissolved in 240 ml. 2-propanol and 90 ml. of sovent is destilled of again. The solution is cooled slowly to 2 0C. The suspension is suction filtered and washed with cold 2-propanol. After drying in a vacuum drying oven at 500C, 38.9 g (79percent of theory) of product 22 is obtained
Reference: [1] Patent: WO2009/19205, 2009, A1, . Location in patent: Page/Page column 13
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Reference: [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 14, p. 5675 - 5690
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4,6-Dichloro-5-nitropyrimidine

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Chemical Structure| 13162-43-1

[ 13162-43-1 ]

4,6-Dichloro-2-methyl-5-nitropyrimidine

Similarity: 0.75

Related Parent Nucleus of
[ 49845-33-2 ]

Pyrimidines

Chemical Structure| 13162-26-0

[ 13162-26-0 ]

2,4-Dichloro-6-methyl-5-nitropyrimidine

Similarity: 0.91

Chemical Structure| 4359-87-9

[ 4359-87-9 ]

2,4,6-Trichloro-5-nitropyrimidine

Similarity: 0.86

Chemical Structure| 10320-42-0

[ 10320-42-0 ]

2-Chloro-5-nitropyrimidine

Similarity: 0.81

Chemical Structure| 4316-93-2

[ 4316-93-2 ]

4,6-Dichloro-5-nitropyrimidine

Similarity: 0.79

Chemical Structure| 5177-27-5

[ 5177-27-5 ]

5-Amino-2,4-dichloropyrimidine

Similarity: 0.76