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Product Details of [ 6602-54-6 ]

CAS No. :6602-54-6 MDL No. :MFCD00014628
Formula : C6H3ClN2 Boiling Point : -
Linear Structure Formula :- InChI Key :JAUPUQRPBNDMDT-UHFFFAOYSA-N
M.W : 138.55 Pubchem ID :81079
Synonyms :

Calculated chemistry of [ 6602-54-6 ]

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 : 0.0
Molar Refractivity : 33.96
TPSA : 36.68 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) : -6.06 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.35
Log Po/w (XLOGP3) : 1.53
Log Po/w (WLOGP) : 1.61
Log Po/w (MLOGP) : 0.4
Log Po/w (SILICOS-IT) : 1.98
Consensus Log Po/w : 1.37

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.16
Solubility : 0.967 mg/ml ; 0.00698 mol/l
Class : Soluble
Log S (Ali) : -1.91
Solubility : 1.71 mg/ml ; 0.0123 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.7
Solubility : 0.278 mg/ml ; 0.002 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.56

Safety of [ 6602-54-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302+H312+H332-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 6602-54-6 ]

* 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 [ 6602-54-6 ]
  • Downstream synthetic route of [ 6602-54-6 ]

[ 6602-54-6 ] Synthesis Path-Upstream   1~39

  • 1
  • [ 6602-54-6 ]
  • [ 13438-65-8 ]
Reference: [1] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[2] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166
  • 2
  • [ 6602-54-6 ]
  • [ 24517-64-4 ]
Reference: [1] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[2] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166
[3] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[4] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166
[5] Patent: WO2003/76442, 2003, A1, . Location in patent: Page/Page column 69
[6] Tetrahedron Letters, 2013, vol. 54, # 25, p. 3233 - 3237
  • 3
  • [ 6602-54-6 ]
  • [ 7664-41-7 ]
  • [ 24517-64-4 ]
Reference: [1] Journal of the American Chemical Society, 1958, vol. 80, p. 421,425
[2] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[3] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166
  • 4
  • [ 6602-54-6 ]
  • [ 64-17-5 ]
  • [ 7664-41-7 ]
  • [ 24517-64-4 ]
Reference: [1] Journal of the American Chemical Society, 1958, vol. 80, p. 421,425
[2] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[3] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166
  • 5
  • [ 6602-54-6 ]
  • [ 20577-27-9 ]
YieldReaction ConditionsOperation in experiment
95% for 48 h; Reflux Acetic acid (826 mL) was added to 2-chloronicotinonitrile (250 g) and mixture was refluxed for 48 h. The reaction mass was poured in ice-water mixture. The precipitate obtained was filtered washed with water and dried to obtain 2-hydroxy-nicotinonitrile. Yield: 95 percent; *H NMR (300 MHz, DMSO-d6): δ 12.57 (s, 1H), 8.16 (dd, J=3, 6Hz, 1H), 7.80 (dd, J=3, 6Hz, 1H), 6.37 (t, 1H); MS (ES): m/z 121.
68% at 120℃; for 8 h; Acetic acid (20 mL) was added in three portions to 2-chloronicotinonitrile (1.38 g, 10 mmol) under stirring at room temperature.
Then, the temperature raised to 120 °C, and kept for 8 h.
After cooled to room temperature, the resulting precipitation was filtered.
2-hydroxynicotinonitrile was obtained as white needle crystal.
Yield: 68percent, 1H NMR (400 MHz, CDCl3): δ: 10.12 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 6.34 (m, 1H).TOF MS (EI+): C6H4N2O, found 121.03. Mp: 224-225 °C.
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 35, p. 6633 - 6636
[2] Patent: WO2014/207508, 2014, A1, . Location in patent: Page/Page column 55
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 18, p. 7624 - 7643
[4] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 21, p. 5738 - 5746
[5] Synthetic Communications, 2011, vol. 41, # 19, p. 2859 - 2869
[6] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 14, p. 4273 - 4278
[7] European Journal of Medicinal Chemistry, 2013, vol. 60, p. 410 - 420
  • 6
  • [ 6602-54-6 ]
  • [ 10366-35-5 ]
YieldReaction ConditionsOperation in experiment
98%
Stage #1: at 90℃; for 2 h;
Stage #2: for 1 h; Cooling with ice
To 1000ml three-necked flask was added concentrated sulfuric acid 400ml, 2-chloronicotinonitrile (138g, 1mol), completely dissolved, warmingTo 90 ° C, stirred for 2 hours,The reaction mixture was poured into a mixture of 1000 ml of ammonia water and 1 kg of ice and stirred for 1 hour. After filtration, the crude solid was obtained by filtration. The crude product was added to 1000 ml of ethyl acetate, stirred for 1 hour and separated by filtration to obtain a white solid. The white solid was further dried by blowing at 50 ° C to afford 153 g of the intermediate 2-chloronicotinamide as a white solid in 98percent yield.
96% With Acetaldehyde oxime; copper(II) oxide In water for 10 h; Reflux General procedure: To a 25 mL round-bottom flask equipped with magnetic stirrer were added nitrile (2.5 mmol), acetaldoxime (3.75 mmol), copper oxide (0.25 mmol) and H2O (10 mL). The mixture was heated to reflux for 2-14 h. After cooling to room temperature, the solution was directly evaporated to dryness and the residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give the corresponding amides. The commercially available amides were characterised by melting points, 2-amino-5-bromobenzamide (Table 2, entry 6) and 3,4-dichloropicolinamide (Table 2, entry 13) were characterised by NMR spectra and LC-MS.
71% With copper(l) iodide; caesium carbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene In nitromethane; water at 20 - 100℃; for 3 h; To a nitromethane (0.1 mL) solution of 2-chloroisophthalonitrile (4i) (30 mg, 0.217 mmol) were addedH2O (1.0 mL), DBU (66 mg, 0.433 mmol), copper (I) iodide (8 mg, 0.0433 mmol), cesium (I)carbonate (35 mg, 0.108 mmol) at room temperature. The reaction mixture was heated at 100 °C for3 h and then poured into water (50 mL). The organic layer was separated and the aqueous layer wasextracted with AcOEt. The combined organic layer was dried over MgSO4. The solvent wasremoved under reduced pressure. The residue was purified by preparative TLC on silica gel elutingwith AcOEt-n-hexane (1:1) to give 2-chloronicotinamide (5i)S12 (24 mg, 71percent) as pale yellow powders.mp 161-163 °C,
Reference: [1] Patent: CN105367571, 2017, B, . Location in patent: Paragraph 0014; 0037; 0038
[2] Tetrahedron Letters, 2012, vol. 53, # 4, p. 449 - 452
[3] Journal of Chemical Research, 2011, vol. 35, # 8, p. 480 - 483
[4] Synlett, 2018, vol. 29, # 15, p. 2061 - 2065
[5] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[6] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166
[7] Synthetic Communications, 1993, vol. 23, # 22, p. 3149 - 3155
  • 7
  • [ 6602-54-6 ]
  • [ 5345-47-1 ]
Reference: [1] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636[2] Org. Synth. Coll., 1963, vol. Vol. IV, p. 166
  • 8
  • [ 6602-54-6 ]
  • [ 36404-88-3 ]
Reference: [1] Journal of Medicinal Chemistry, 1988, vol. 31, # 3, p. 618 - 624
[2] Chemical and Pharmaceutical Bulletin, 2002, vol. 50, # 8, p. 1066 - 1072
[3] Patent: US5624935, 1997, A,
[4] Patent: US4619930, 1986, A,
[5] Patent: US4757073, 1988, A,
[6] Journal of Medicinal Chemistry, 2008, vol. 51, # 13, p. 4021 - 4029
[7] Patent: EP1726590, 2006, A1, . Location in patent: Page/Page column 47
  • 9
  • [ 6602-54-6 ]
  • [ 3939-13-7 ]
YieldReaction ConditionsOperation in experiment
69% With cesium fluoride In dimethyl sulfoxide at 90℃; for 2 h; General procedure: To a solution of 2,3-dichloropyridine(1.00 g, 6.76 mmol) in DMSO (33.8 ml) was added CsF (2.053 g, 13.51mmol) at room temperature. The mixture was stirred at 110 °C under air for 20h. The mixture was quenched with water at room temperature and extracted withEtOAc. The organic layer was separated, washed with water and brine, dried overNa2SO4 and concentrated in vacuo. The residue waspurified by column chromatography (silica gel, eluted with EtOAc in hexane) togive 3-chloro-2-fluoropyridine (0.639 g, 4.86 mmol, 71.9 percent) as colorlessoil. Thecompound 3B'-8B' were prepared in amanner similar to that described for 2B'.
Reference: [1] European Journal of Inorganic Chemistry, 2017, vol. 2017, # 2, p. 330 - 339
[2] Tetrahedron Letters, 2015, vol. 56, # 44, p. 6043 - 6046
[3] Heterocycles, 1992, vol. 34, # 8, p. 1507 - 1510
[4] Organic Letters, 2015, vol. 17, # 8, p. 1866 - 1869
[5] Journal of Organic Chemistry, 2015, vol. 80, # 24, p. 12137 - 12145
  • 10
  • [ 100-54-9 ]
  • [ 6602-54-6 ]
  • [ 89284-61-7 ]
Reference: [1] Tetrahedron Letters, 2005, vol. 46, # 1, p. 135 - 137
[2] Synthesis, 2007, # 20, p. 3247 - 3251
  • 11
  • [ 14906-64-0 ]
  • [ 33252-28-7 ]
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  • [ 89284-61-7 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1988, vol. 36, p. 2244 - 2247
  • 12
  • [ 1986-81-8 ]
  • [ 33252-28-7 ]
  • [ 6602-54-6 ]
  • [ 89284-61-7 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1988, vol. 36, p. 2244 - 2247
  • 13
  • [ 6602-54-6 ]
  • [ 20577-26-8 ]
Reference: [1] Tetrahedron, 2012, vol. 68, # 34, p. 6941 - 6947
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3013 - 3032
  • 14
  • [ 6602-54-6 ]
  • [ 6752-16-5 ]
YieldReaction ConditionsOperation in experiment
100% With hydrazine In ethanol at 170℃; for 0.166667 h; Microwave irradiation Example 8; [00146] Compound 7 (1.4 mmol) was dissolved in EtOH (10 mL) in a microwave tube, to which 5 equivalent of NH2NH2 was added, and the reaction mixture was heated by microwave irradiation for 10 min at 170aC. Evaporated the solvent to obtain the compound 8 in quantitative yield.
47% With hydrazine hydrate; caesium carbonate In N,N-dimethyl-formamide at 60℃; 2-Chloronicotinonitrile (0.75 g, 5.30 mmol), cupper iodide (I) (50 mg, 0.05 mmol), cesium carbonate (2.59 g, 7.96 mmol) and 1,10-phenanthroline (96 mg, 0.53 mmol) were suspended in 20 mL of dimethylformamide.
Hydrazine hydrate (1.6 mL, 31.83 mmol) was added and the mixture was stirred at 60°C overnight.
The mixture was cooled to room temperature, water was added and the aqueous phase was extracted with dichloromethane (x3).
The combined organic layers were dried with magnesium sulphate, filtered and evaporated.
The crude was purified by column chromatography using the SP1 Purification system (methanol-dichloromethane gradient) to yield 0.34 g (2.51 mmol, 47percent) of the title compound as a yellow solid. Purity:100percent.
1H NMR (200 MHz, DMSO-d6) δ ppm 11.91 (1 H, br. s.), 8.33 (1 H, dd, J=4.3, 1.6 Hz), 8.10 (1 H, dd, J=7.8, 1.6 Hz), 6.94 (1 H, dd, J=7.8, 4.7 Hz), 5.55 (2 H, s).
LRMS: m/z 135 (M+1).
Reference: [1] Patent: WO2007/59219, 2007, A1, . Location in patent: Page/Page column 56
[2] Chemical Communications, 2014, vol. 50, # 85, p. 12911 - 12914
[3] Canadian Journal of Chemistry, 1988, vol. 66, # 3, p. 420-428
[4] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 4, p. 763 - 767
[5] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 361 - 371
[6] Tetrahedron Letters, 2004, vol. 45, # 11, p. 2389 - 2392
[7] Tetrahedron, 2015, vol. 71, # 34, p. 5597 - 5601
[8] Patent: EP2380890, 2011, A1, . Location in patent: Page/Page column 36
[9] Journal of Medicinal Chemistry, 2018, vol. 61, # 6, p. 2472 - 2489
[10] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 13, p. 4763 - 4772
  • 15
  • [ 6602-54-6 ]
  • [ 60-34-4 ]
  • [ 72583-83-6 ]
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 11, p. 2389 - 2392
[2] Farmaco, 2005, vol. 60, # 6-7, p. 513 - 517
[3] Canadian Journal of Chemistry, 1988, vol. 66, # 3, p. 420-428
  • 16
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  • [ 271-73-8 ]
Reference: [1] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 361 - 371
  • 17
  • [ 6602-54-6 ]
  • [ 5271-27-2 ]
  • [ 61338-13-4 ]
  • [ 61337-88-0 ]
Reference: [1] Patent: US2002/95038, 2002, A1,
  • 18
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  • [ 61338-13-4 ]
Reference: [1] Organic Preparations and Procedures International, 2007, vol. 39, # 4, p. 399 - 402
[2] Patent: CN105367571, 2017, B,
  • 19
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  • [ 61337-89-1 ]
Reference: [1] Organic Preparations and Procedures International, 2007, vol. 39, # 4, p. 399 - 402
[2] Patent: CN105367571, 2017, B,
  • 20
  • [ 6602-54-6 ]
  • [ 676-58-4 ]
  • [ 55676-21-6 ]
Reference: [1] Organic and Biomolecular Chemistry, 2010, vol. 8, # 22, p. 5166 - 5173
  • 21
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  • [ 917-64-6 ]
  • [ 55676-21-6 ]
Reference: [1] Zeitschrift fuer Chemie (Stuttgart, Germany), 1990, vol. 30, # 7, p. 245 - 246
  • 22
  • [ 6602-54-6 ]
  • [ 2365-48-2 ]
  • [ 111042-89-8 ]
Reference: [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 6, p. 2606 - 2618
[2] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 85 - 89
[3] ChemMedChem, 2014, vol. 9, # 11, p. 2587 - 2601
[4] ChemMedChem, 2014, vol. 9, # 11, p. 2587 - 2601
[5] Organic and Biomolecular Chemistry, 2015, vol. 13, # 24, p. 6814 - 6824
  • 23
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  • [ 133627-47-1 ]
Reference: [1] Patent: WO2016/118586, 2016, A1,
[2] Green Chemistry, 2017, vol. 19, # 13, p. 2986 - 2991
  • 24
  • [ 6602-54-6 ]
  • [ 546-88-3 ]
  • [ 92914-74-4 ]
YieldReaction ConditionsOperation in experiment
48%
Stage #1: With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane at 20℃; for 2 h; Inert atmosphere
Stage #2: at 20℃; for 25 h; Inert atmosphere
Method 1. Representative example
Isoxazolo[5,4-b]pyridin-3-amine (2)
From 2-chloronicotinonitrile in 1,2-dimethoxyethane in 48percent yield
Reference: [1] Patent: WO2016/24233, 2016, A1, . Location in patent: Page/Page column 33
  • 25
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  • [ 92914-74-4 ]
Reference: [1] Acta Poloniae Pharmaceutica - Drug Research, 2003, vol. 60, # 4, p. 293 - 301
[2] Green Chemistry, 2016, vol. 18, # 18, p. 4941 - 4946
[3] Acta Poloniae Pharmaceutica - Drug Research, 2003, vol. 60, # 4, p. 293 - 301
  • 26
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  • [ 114080-94-3 ]
Reference: [1] Zeitschrift fuer Chemie (Stuttgart, Germany), 1987, vol. 27, # 9, p. 337 - 338
  • 27
  • [ 6602-54-6 ]
  • [ 116855-03-9 ]
Reference: [1] Canadian Journal of Chemistry, 1988, vol. 66, # 3, p. 420-428
[2] Canadian Journal of Chemistry, 1988, vol. 66, # 3, p. 420-428
  • 28
  • [ 6602-54-6 ]
  • [ 117007-52-0 ]
Reference: [1] Tetrahedron, 2015, vol. 71, # 34, p. 5597 - 5601
[2] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 361 - 371
  • 29
  • [ 6602-54-6 ]
  • [ 205744-14-5 ]
Reference: [1] Tetrahedron Letters, 2010, vol. 51, # 31, p. 4053 - 4057
  • 30
  • [ 6602-54-6 ]
  • [ 405224-23-9 ]
Reference: [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 18, p. 7624 - 7643
  • 31
  • [ 6602-54-6 ]
  • [ 405224-24-0 ]
Reference: [1] Patent: WO2012/101239, 2012, A1,
[2] Patent: US2013/85144, 2013, A1,
[3] Patent: EP2689778, 2014, A1,
[4] Patent: EP2689779, 2014, A1,
[5] Patent: WO2014/16433, 2014, A1,
[6] Patent: WO2014/16434, 2014, A1,
[7] Patent: KR2017/46848, 2017, A,
  • 32
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  • [ 371935-74-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 9, p. 2438 - 2442
  • 33
  • [ 6602-54-6 ]
  • [ 623-50-7 ]
  • [ 371945-06-1 ]
YieldReaction ConditionsOperation in experiment
70% at 70℃; for 4 h; To a stirred mixture of the pyridine 51a (2.00 g, 1.0 eq), the alcohol 51b (1.43 mL, 1.05 eq), CuI (0.05 g, 0.02 eq) is added Cs2CO3 (10.3 g, 2.2 eq) and heated at 70° C. during4 h. The reaction mixture is cooled down to RT, poured into H2O (300 mL) and allowed to stand for 1 h until precipitation. The suspension is filtered, triturated with Et2O/Hex (1:1), dried with toluene azeotrope to give 51c (2.0 g, 70percent).
50% With caesium carbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 80℃; for 24 h; Inert atmosphere 2- Chloro 3-pyridine carbonitrile (1, 2.0 g, 1 equiv.), Cs2C03 (14.2 g, 3 equiv.) and ethyl glycolate (1.5 mL, 1.2 equiv.) were placed in a flask under inert atmosphere. Dry toluene and DBU (4.3 mL, 2 equiv) were added and the suspension was heated at 80 °C for 24 h with vigorous stirring. The reaction mixture was cooled to RT, and then water and EtOAc were added. The organic layer was seperated and was washed with water before being dried over anhydrous Na2S04 and concentrated in vacuo. Purification was done by column chromatography on silica gel using 10-40percent EtOAC: hexane as a mobile phase to get product 2 (1.5 g, 50percent) as a white solid. *H NMR (CDC13, 400 MHz): δ 8.51 (dd, / = 5.0, 2.0 Hz, 1H), 7.96 (dd, / = 8.0, 2.0 Hz, 1H), 7.23-7.28 (m,1H), 4.44 (q, / = 7.0 Hz, 2H), 4.01 (br, s, 2H), 1.44 (t, / = 7.0 Hz, 3H); ESI-MS: nt/z 229.05 [M+Na]+
40% With caesium carbonate In 1-methyl-pyrrolidin-2-one at 75℃; for 20 h; Inert atmosphere 2-Chloro-3-pyridinecarbonitrile, 1 , (4.0Og, 28.9mmol), Cs2CO3 (28.2g, 86.6mmol) and ethyl glycolate (3mL, 31.7mmol) were placed in a flask under Ar(g). Dry NMP was added, and the suspension was heated at 75°C for 2Oh with vigorous stirring. The reaction mixture was cooled to rt, whereupon water (200 mL) and Et2ψ (3 x 10OmL) were added. The organic layers were combined, washed with water (3 x 15mL) before being dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica (eluant 15-40percent EtOAc/Hex) gave 2 (2.41 g, 1 1 Jmmol, 40percent) as a white solid.1H NMR (400MHz, CDCI3) δH: 8.51 (dd, J=5.0, 2.0Hz, 1 H), 7.96 (dd, J=8.0, 2.0Hz, 1 H), 7.23-7.28 (m, 1 H), 4.44 (q, J=7.0Hz, 2H), 4.01 (br. s., 2H), 1.44 (t, J=7.0Hz, 3H).MS (ES+) 229 (100percent, [M+Na]+).
Reference: [1] Patent: US2010/261714, 2010, A1, . Location in patent: Page/Page column 75
[2] Synthesis, 2007, # 20, p. 3247 - 3251
[3] Patent: WO2017/90058, 2017, A1, . Location in patent: Page/Page column 14
[4] Patent: WO2011/21038, 2011, A1, . Location in patent: Page/Page column 18; 24
[5] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 2, p. 138 - 142
[6] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 9, p. 2438 - 2442
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  • [ 765-30-0 ]
  • [ 639807-18-4 ]
Reference: [1] Patent: US2004/2603, 2004, A1, . Location in patent: Page 4-5
  • 35
  • [ 6602-54-6 ]
  • [ 639807-18-4 ]
Reference: [1] Green Chemistry, 2017, vol. 19, # 13, p. 2986 - 2991
  • 36
  • [ 6602-54-6 ]
  • [ 39971-65-8 ]
  • [ 386704-06-9 ]
Reference: [1] Journal of the American Chemical Society, 2013, vol. 135, # 32, p. 12122 - 12134
  • 37
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  • [ 956010-88-1 ]
Reference: [1] Tetrahedron, 2015, vol. 71, # 34, p. 5597 - 5601
  • 38
  • [ 6602-54-6 ]
  • [ 1171919-75-7 ]
YieldReaction ConditionsOperation in experiment
19%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78 - -30℃; for 1 h; Inert atmosphere
Stage #2: With iodine In tetrahydrofuran; hexane at -78℃; for 0.5 h;
Step 1:
Synthesis of 2-chloro-4-iodonicotinonitrile
In an atmosphere of argon gas, at -30° C., n-butyl lithium (2.4M hexane solution, 3.0 mL, 7.2 mmol) was added dropwise to a solution of diisopropylamine (0.728 g, 7.2 mmol) in anhydrous tetrahydrofuran (20 mL) to get a reaction mixture.
The reaction mixture was stirred at -30° C. for 30 minutes, and then cooled to -78° C. A solution of 2-chloro-nicotinonitrile (1.0 g, 7.2 mmol) in anhydrous tetrahydrofuran (10 mL) was added dropwise, and the reaction mixture was then stirred at -78° C. for 60 minutes.
A solution of iodine (1.8 g, 7.2 mmol) in anhydrous tetrahydrofuran (10 mL) was added dropwise, and the reaction mixture was then stirred at -78° C. for 30 minutes.
The reaction mixture was quenched with saturated ammonium chloride solution (50 mL), diluted with water (50 mL), and extracted with ethyl acetate (100 mL*3).
The organic phases were combined.
The combined organic phases were washed with saline solution (100 mL*3), dried with anhydrous sodium sulfate, filtrated, and concentrated.
The residue was purified by column chromatography (petroleum ether:ethyl acetate=80:1) to get product as yellow solid (0.357 g, yield: 19percent).
1H NMR (400 MHz, DMSO-d6) δ 8.32 (d, J=5.2 Hz, 1H), 8.15 (d, J=5.2 Hz, 1H)
MS (ESI+): m/z 264.9 [M+H]+
Reference: [1] Patent: US2017/29404, 2017, A1, . Location in patent: Paragraph 0155-0158
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  • [ 941294-54-8 ]
Reference: [1] Patent: WO2012/101239, 2012, A1,
[2] Patent: US2013/85144, 2013, A1,
[3] Patent: EP2689778, 2014, A1,
[4] Patent: EP2689779, 2014, A1,
[5] Patent: WO2014/16433, 2014, A1,
[6] Patent: WO2014/16434, 2014, A1,
[7] Patent: KR2017/46848, 2017, A,
Same Skeleton Products
Historical Records

Pharmaceutical Intermediates of
[ 6602-54-6 ]

Nevirapine Related Intermediates

Chemical Structure| 21901-18-8

[ 21901-18-8 ]

4-Methyl-3-nitropyridin-2(1H)-one

Chemical Structure| 133627-45-9

[ 133627-45-9 ]

2-Chloro-4-methylpyridin-3-amine

Chemical Structure| 23056-39-5

[ 23056-39-5 ]

2-Chloro-4-methyl-3-nitropyridine

Chemical Structure| 639807-18-4

[ 639807-18-4 ]

2-(Cyclopropylamino)nicotinic acid

Chemical Structure| 2942-59-8

[ 2942-59-8 ]

2-Chloronicotinic acid

Related Functional Groups of
[ 6602-54-6 ]

Chlorides

Chemical Structure| 66909-33-9

[ 66909-33-9 ]

2-Chloro-5-cyano-3-picoline

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Chemical Structure| 40381-90-6

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2,6-Dichloropyridine-3-carbonitrile

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Chemical Structure| 791644-48-9

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2-Chloro-5-fluoronicotinonitrile

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Chemical Structure| 33252-30-1

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Chemical Structure| 72093-11-9

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2-Chloro-3,4-dimethylpyridine

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Nitriles

Chemical Structure| 66909-33-9

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2,6-Dichloropyridine-3-carbonitrile

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2-Chloro-5-fluoronicotinonitrile

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Chemical Structure| 33252-30-1

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2-Chloroisonicotinonitrile

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Related Parent Nucleus of
[ 6602-54-6 ]

Pyridines

Chemical Structure| 66909-33-9

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2-Chloro-5-cyano-3-picoline

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2,6-Dichloropyridine-3-carbonitrile

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2-Chloro-5-fluoronicotinonitrile

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Chemical Structure| 33252-30-1

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Chemical Structure| 72093-11-9

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2-Chloro-3,4-dimethylpyridine

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