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[ CAS No. 387-45-1 ] {[proInfo.proName]}

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Chemical Structure| 387-45-1
Chemical Structure| 387-45-1
Structure of 387-45-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 387-45-1 ]

CAS No. :387-45-1 MDL No. :MFCD00003306
Formula : C7H4ClFO Boiling Point : -
Linear Structure Formula :- InChI Key :OACPOWYLLGHGCR-UHFFFAOYSA-N
M.W : 158.56 Pubchem ID :67847
Synonyms :

Calculated chemistry of [ 387-45-1 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 36.8
TPSA : 17.07 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) : -5.77 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.51
Log Po/w (XLOGP3) : 2.11
Log Po/w (WLOGP) : 2.71
Log Po/w (MLOGP) : 2.48
Log Po/w (SILICOS-IT) : 3.04
Consensus Log Po/w : 2.37

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.53
Solubility : 0.468 mg/ml ; 0.00295 mol/l
Class : Soluble
Log S (Ali) : -2.1
Solubility : 1.26 mg/ml ; 0.00796 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.23
Solubility : 0.0938 mg/ml ; 0.000592 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.33

Safety of [ 387-45-1 ]

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

Application In Synthesis of [ 387-45-1 ]

* 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 [ 387-45-1 ]
  • Downstream synthetic route of [ 387-45-1 ]

[ 387-45-1 ] Synthesis Path-Upstream   1~25

  • 1
  • [ 387-45-1 ]
  • [ 13096-96-3 ]
YieldReaction ConditionsOperation in experiment
62% With hydrazine hydrate In 1,2-dimethoxyethaneReflux A solution of 2-chloro-6-fluorobenzaldehyde (10 g, 63.07 mmol, 1.00 equiv) and hydrazine hydrate (80percent, 20 g, 399.52 mmol, 6.30 equiv) in ethylene glycol dimethyl ether (20 mL, 206.63mmol, 3.30 equiv) was heated to reflux overnight. The reaction was quenched by water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified on a silica gel column eluting with ethyl acetate/petroleum ether (1:10) to give 6 g (62percent) of the title compound as a yellow solid. LC-MS (ES, m/z): 153 [M+H].Step 2: Synthesis of 4-chloro-3-iodo-1H-indazole
52% With hydrazine hydrate In 1,2-dimethoxyethaneReflux Example 174[0438] (5)-N-(benzo[ ][l,3]dioxol-5-yl)-2-(2-(4-chloro-3-(2-hydroxyethyl)-lH-indazol- 1 -yl)acetamido)-N-methyl-3 -phenylpropanamideExample 174A. Preparation of 4-chloro-lH-indazole[0439] Hydrazine hydrate (85percent, 50 mL) was added over a period of 10 minutes to a solution of 2-chloro-6-fluorobenzaldehyde (5.0 g, 31.6 mmol, 1.0 eq) in DME (50 mL). The reaction mixture was re fluxed overnight and concentrated in vacuum to approximately 50 mL. Water (50 mL) was added to the mixture. The resulting solid precipitate was collected by filtration and dried to give 4-chloro-lH-indazole (2.5 g, 16.4 mmol, yield: 52percent), LC/MS: m/z M++l = 153.
Reference: [1] Patent: US2007/244178, 2007, A1, . Location in patent: Page/Page column 12
[2] Patent: WO2015/25025, 2015, A1, . Location in patent: Page/Page column 166
[3] Patent: WO2012/65062, 2012, A1, . Location in patent: Page/Page column 122
[4] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8166 - 8172
  • 2
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  • [ 13096-96-3 ]
Reference: [1] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8166 - 8172
  • 3
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  • [ 20925-60-4 ]
Reference: [1] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8166 - 8172
  • 4
  • [ 387-45-1 ]
  • [ 434-75-3 ]
YieldReaction ConditionsOperation in experiment
99% With sodium chlorite; sodium dihydrogenphosphate; dihydrogen peroxide In tetrahydrofuran; water at 20℃; for 3 h; To the solution of 2-chloro-6-fluorobenzaidehyde {1 ,0 g, 6.31 mmoi) in 25 mL of THF and 10 ml of H2O was added 8H2PO4 (454 rng, 3.78 mmoi). The reaction was stirred 10 min at room temperature before introduction of NaCiC (1.88 g, 20.8.1 mmoi) and 1 ,4 mL of H2O2 (30percentwt ..in H2O), The reaction was stirred at room temperature 3h, Upon completion, the reaction mixture was extracted with EtOAc. The combined organic layers were washed with an aqueous solution of NaOH 1 .. The combined aqueous layers were acidified to pH-1 'with an aqueous solution of HG 1 and wer extracted with EtOAc. The combined organic layers were washed with brine and dried over >SQ . Filtration and removal of the solven in. vacuo provided 1.10 g (99percent) of the title compound as a colorless solid which was used without further purification; FontWeight="Bold" FontSize="10" H NMR (400 MHz, CDC ) δ - 7.44 - 7.37 (m, 1 H), 7.31 - 7.27 (m, 1 H), 7.1 - 7,07 (m, 1 H},
Reference: [1] ChemMedChem, 2016, vol. 11, # 23, p. 2607 - 2620
[2] Patent: WO2018/52903, 2018, A1, . Location in patent: Page/Page column 47-48
[3] Tetrahedron Letters, 1988, vol. 29, # 16, p. 1967 - 1970
[4] Chemische Berichte, 1936, vol. 69, p. 2253,2255
[5] Tetrahedron Letters, 1988, vol. 29, # 16, p. 1967 - 1970
  • 5
  • [ 387-45-1 ]
  • [ 437-81-0 ]
Reference: [1] Patent: WO2003/101926, 2003, A1, . Location in patent: Page 18, 19
[2] Patent: WO2003/101926, 2003, A1, . Location in patent: Page 18, 19
[3] Patent: WO2003/101926, 2003, A1, . Location in patent: Page 18, 19
[4] Patent: WO2003/101926, 2003, A1, . Location in patent: Page 18, 19
[5] Patent: WO2003/101926, 2003, A1, . Location in patent: Page 18, 19
[6] Patent: WO2003/101926, 2003, A1, . Location in patent: Page 18, 19
[7] Patent: WO2003/101926, 2003, A1, . Location in patent: Page 18, 19
[8] Patent: US6465643, 2002, B1,
[9] Patent: WO2004/74296, 2004, A2, . Location in patent: Page/Page column 12-13
[10] Patent: WO2004/74296, 2004, A2, . Location in patent: Page/Page column 13
[11] Patent: WO2004/74296, 2004, A2, . Location in patent: Page/Page column 13
  • 6
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  • [ 387-45-1 ]
Reference: [1] Journal of Fluorine Chemistry, 1990, vol. 46, # 3, p. 529 - 537
[2] Journal of Fluorine Chemistry, 2004, vol. 125, # 6, p. 1031 - 1038
[3] Journal of Fluorine Chemistry, 1990, vol. 46, # 3, p. 529 - 537
  • 7
  • [ 387-45-1 ]
  • [ 29866-54-4 ]
YieldReaction ConditionsOperation in experiment
64.2% With sodium hydroxide In methanol; hexane; dichloromethane; water PREPARATION 12
2-Chloro-6-methoxybenzaldehyde
2-Chloro-6-fluorobenzaldehyde (51.5 g., 0.030 mole) was taken into 500 ml. of methanol.
Sodium hydroxide (14.4 g., 0.35 mole) was added and the stirred reaction mixture heated to reflux for 3 hours.
The mixture was cooled to room temperature, and the volume reduced to 200 ml. by distillation in vacuo.
Water (400 ml.) and methylene chloride (200 ml.) were added and the two phase system equilibrated.
The organic phase was separated and the aqueous phase extracted with two additional 100 ml. portions of methylene chloride.
The combined organic layers were dried over anhydrous sodium sulfate, filtered and the methylene chloride removed by distillation at atmospheric pressure with displacement by hexane (450 ml.) to a final volume of 300 ml.
The product layer, initially present as an oil, began to crystallize at 45° C.
The mixture was cooled to room temperature, granulated for 16 hours, and filtered to yield 2-chloro-6-methoxybenzaldehyde [35.6 g., 64.2percent; Rf 0.2 (CHCl3)].
Reference: [1] Patent: US4367234, 1983, A,
  • 8
  • [ 67-56-1 ]
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  • [ 29866-54-4 ]
Reference: [1] Gazzetta Chimica Italiana, 1993, vol. 123, # 11, p. 617 - 622
  • 9
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  • [ 18362-30-6 ]
YieldReaction ConditionsOperation in experiment
62%
Stage #1: With potassium hydroxide In dimethyl sulfoxide at 0 - 20℃; for 18 h;
Stage #2: With hydrogenchloride In water; dimethyl sulfoxide
Potassium hydroxide (10 g) was added slowly to a stirred solution of 2-chloro-6-fluoro- benzaldehyde (14.0 g, 88.3 mmol) in dimethylsulfoxide (20 mL) at 0°C, the reaction mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was diluted with water (100 mL) and acidified to pH 2 with concentrated HCl. The precipitates were filtered, washed with water (2x100 mL) and dried over anhydrous sodium sulfate, to give a residue which was used directly in the next step. Yield: 8.5 g (62percent). H NMR (400 MHz, CDCI3) δ ppm 6.85 - 7.02 (m, 2H) 7.39 - 7.47 (m, 1H) 10.41 (s, 1H) 11.95 (s, 1H).
61%
Stage #1: With potassium hydroxide In dimethyl sulfoxide at 0 - 20℃;
Stage #2: With hydrogenchloride; water In dimethyl sulfoxide
2-chloro-6-hydroxybenzaldehyde
To a solution of 2-chloro-6-fluorobenzaldehyde (2.44 g, 15.4 mmol) in DMSO (20 mL) at 0° C. was added potassium hydroxide (2.23 g, 33.8 mmol) slowly.
The reaction mixture was allowed to stir and warm to rt overnight and then diluted with water (65 mL).
The mixture was acidified to pH<1 with conc. HCl.
A white solid formed and was filtered, washed with water, and dried to give 2-chloro-6-hydroxybenzaldehyde (1.48 g, 61percent). LCMS: (FA) ES-155.0.
Reference: [1] European Journal of Organic Chemistry, 2018, vol. 2018, # 25, p. 3348 - 3351
[2] Patent: WO2012/87229, 2012, A1, . Location in patent: Page/Page column 14
[3] Patent: US2008/171754, 2008, A1, . Location in patent: Page/Page column 89
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 12, p. 1345 - 1358
[5] Zeitschrift fuer Naturforschung, Teil B: Anorganische Chemie, Organische Chemie, Biochemie, Biophysik, Biologie, 1972, vol. 27, p. 663 - 674
[6] Journal of the Chemical Society, Chemical Communications, 1994, # 14, p. 1697 - 1698
[7] Patent: US5149357, 1992, A,
  • 10
  • [ 56456-50-9 ]
  • [ 387-45-1 ]
YieldReaction ConditionsOperation in experiment
91% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium carbonate; N-Phenylglycine; copper(ll) bromide In water for 8 h; Reflux; Schlenk technique General procedure: A mixture of p-methylbenzyl alcohol (1.0 mmol), N-phenylglycine(0.0076 g, 0.05 mmol), CuBr2 (0.0112 g, 0.05 mmol),Na2CO3 (0.1060 g, 1.0 mmol), TEMPO (0.0078 g, 0.05 mmol),H2O (3.0 mL) were added to a 100 mL Schlenk tube, which wasvigorously stirred in air under reflux for 0.5 h. After the reaction,the product was extracted with CH2Cl2 (3 × 2.0 mL). Thecombined organic phase was washed with H2O (3.0 mL) anddried over anhydrous MgSO4. After concentration undervacuum, the residue was purified by column chromatography toafford p-methylbenzaldehyde.Isolated yield: 0.1080 g (90percent).
Reference: [1] Synthetic Communications, 2008, vol. 38, # 15, p. 2638 - 2645
[2] Journal of the American Chemical Society, 2011, vol. 133, # 42, p. 16901 - 16910
[3] RSC Advances, 2014, vol. 4, # 90, p. 48777 - 48782
[4] Journal of Organic Chemistry, 2015, vol. 80, # 21, p. 11184 - 11188
[5] Synlett, 2015, vol. 26, # 6, p. 779 - 784
[6] Synthetic Communications, 2009, vol. 39, # 2, p. 366 - 370
[7] Advanced Synthesis and Catalysis, 2014, vol. 356, # 8, p. 1741 - 1746
  • 11
  • [ 443-33-4 ]
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Reference: [1] RSC Advances, 2013, vol. 3, # 45, p. 22918 - 22921
  • 12
  • [ 625-98-9 ]
  • [ 68-12-2 ]
  • [ 387-45-1 ]
Reference: [1] Tetrahedron Letters, 2013, vol. 54, # 45, p. 6053 - 6056
  • 13
  • [ 661452-15-9 ]
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Reference: [1] Synthetic Communications, 2008, vol. 38, # 10, p. 1629 - 1637
  • 14
  • [ 83-38-5 ]
  • [ 437-81-0 ]
  • [ 387-45-1 ]
Reference: [1] Journal of Fluorine Chemistry, 1990, vol. 46, # 3, p. 529 - 537
[2] Journal of Fluorine Chemistry, 2004, vol. 125, # 6, p. 1031 - 1038
[3] Journal of Fluorine Chemistry, 1990, vol. 46, # 3, p. 529 - 537
  • 15
  • [ 89-98-5 ]
  • [ 387-45-1 ]
Reference: [1] Journal of the American Chemical Society, 2018, vol. 140, # 8, p. 2789 - 2792
  • 16
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Reference: [1] Patent: US6465643, 2002, B1,
  • 17
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Reference: [1] Chemische Berichte, 1936, vol. 69, p. 2253,2255
[2] Chemische Berichte, 1931, vol. 64, p. 2688,2692
  • 18
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  • [ 7726-95-6 ]
  • [ 387-45-1 ]
Reference: [1] Chemische Berichte, 1936, vol. 69, p. 2253,2255
  • 19
  • [ 387-45-1 ]
  • [ 68220-26-8 ]
Reference: [1] ChemMedChem, 2016, vol. 11, # 23, p. 2607 - 2620
[2] Patent: WO2018/52903, 2018, A1,
  • 20
  • [ 387-45-1 ]
  • [ 21327-86-6 ]
Reference: [1] Organic Process Research and Development, 2002, vol. 6, # 3, p. 220 - 224
  • 21
  • [ 387-45-1 ]
  • [ 77491-27-1 ]
  • [ 21327-86-6 ]
Reference: [1] Patent: WO2017/161116, 2017, A1, . Location in patent: Paragraph 00429
  • 22
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  • [ 35490-90-5 ]
Reference: [1] Patent: WO2007/82809, 2007, A1, . Location in patent: Page/Page column 7
  • 23
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  • [ 1847-24-1 ]
Reference: [1] Patent: WO2012/164355, 2012, A1,
  • 24
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  • [ 2365-48-2 ]
  • [ 35212-95-4 ]
Reference: [1] Patent: US2003/166628, 2003, A1,
  • 25
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  • [ 518990-33-5 ]
Reference: [1] Patent: WO2015/25025, 2015, A1,
[2] Patent: WO2012/65062, 2012, A1,
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