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Product Details of [ 49608-01-7 ]

CAS No. :49608-01-7 MDL No. :MFCD00082739
Formula : C8H8ClNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :ILDJJTQWIZLGPO-UHFFFAOYSA-N
M.W : 185.61 Pubchem ID :2799611
Synonyms :

Calculated chemistry of [ 49608-01-7 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.25
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 45.33
TPSA : 39.19 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) : -5.81 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.18
Log Po/w (XLOGP3) : 2.28
Log Po/w (WLOGP) : 1.91
Log Po/w (MLOGP) : 1.25
Log Po/w (SILICOS-IT) : 2.16
Consensus Log Po/w : 1.96

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.6
Solubility : 0.467 mg/ml ; 0.00252 mol/l
Class : Soluble
Log S (Ali) : -2.74
Solubility : 0.338 mg/ml ; 0.00182 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.12
Solubility : 0.14 mg/ml ; 0.000753 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.72

Safety of [ 49608-01-7 ]

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 [ 49608-01-7 ]

* 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 [ 49608-01-7 ]
  • Downstream synthetic route of [ 49608-01-7 ]

[ 49608-01-7 ] Synthesis Path-Upstream   1~14

  • 1
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  • [ 39658-41-8 ]
Reference: [1] Tetrahedron Letters, 2013, vol. 54, # 5, p. 414 - 418
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  • [ 98-80-6 ]
  • [ 29051-44-3 ]
YieldReaction ConditionsOperation in experiment
69% With tetrakis(triphenylphosphine) palladium(0); water; sodium carbonate In 1,4-dioxane at 110℃; for 18 h; To a stirred solution of compound A (3 g, 16.16 mmol, 1 eq) in a mixture of dioxane and water (150 mL, 4: 1) mixture were added compound B (3 g, 24.2 mmol, 1.5 eq) and sodium carbonate (8.6 g, 80.8 mmol, 5 eq) and the mixture was degassed with argon for 30 minutes. Pd(Ph3P)4 (1.9 g, 1.62 mmol, 0.1 eq) was added to it and the resulting mixture was further degassed with argon for another 10 minutes and stirred at 110 °C for 18 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was diluted with water (30 mL) and washed with ethyl acetate (20 mL). The aq. part was acidified with saturated aq. citric acid solution to pH 5. The organic components were extracted with 10percent MeOHZ CH2CI2 (100 mL) and the organic layer was concentrated in vacuo to obtain the compound C (2.2 g, 69percent) as white solid which was used in the next step without further purification. (0315) [0305] FontWeight="Bold" FontSize="10" H NMR (400 MHz, DMSO-cfe) δ 13.4(br s, 1 H), 9.14 (d, / = 2 Hz, 1 H), 8.33- 8.31 (m, 1 H), 8.17-8.15 (m, 2 H), 8.10 (d, / = 8 Hz, 1H), 7.55-7.48 (m, 3 H); (0316) [0306] LCMS: m/z = 200.1 [M+H], RT = 3.21 minutes; (Program Rl, Column Y).
Reference: [1] Patent: WO2018/64135, 2018, A1, . Location in patent: Paragraph 0303-0306
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  • [ 1970-80-5 ]
Reference: [1] Journal of the American Chemical Society, 1992, vol. 114, # 3, p. 825 - 831
  • 4
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  • [ 21543-49-7 ]
YieldReaction ConditionsOperation in experiment
59% With sodium tetrahydroborate In methanol at 0 - 20℃; for 16 h; To a solution of 19-2B (500 mg, 2.693 mmol) in MeOH (5 mL) was added sodium borohydride (153 mg, 4.04 mmol) portion wise at 0 °C and stirred at RT for 16 hr. The reaction was quenched with saturated ammonium chloride and diluted with EtOAc (50 mL) washed with water (50 mL), brine (20 mL) and dried over Na2S04, and the organic phase was concentrated under reduced pressure to get crude compound. Obtained crude was purified using silica gel chromatography (30percent EtOAc in hexanes) to afford 19-3B (230 mg, 1.60 mmol, 59percent yield) as a pale yellow solid. MS (ESI): m/z 144.0 (M+l)+.
58% With sodium tetrahydroborate In ethanol at 20℃; for 41 h; To a solution of ethyl 6-chloronicotinate (25.8 g, 0.139 mol) in ethanol was added sodium borohydride (10.5 g, 0.278 mol), followed by stirring under an atmosphere of nitrogen gas at room temperature. After 41 hours, the reaction mixture was concentrated and then the residue was diluted with a saturated aqueous ammonium chloride solution and ethyl acetate. The organic layer was washed with a saturated aqueous ammonium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was subjected to silica gel column chromatography (elution solvent; hexane, hexane:ethyl acetate=4:1, 2:1, and 3:2), to give the title compound (11.7 g, 58percent) as a pale yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm; 4.54 (2H, d, J=5.6Hz), 5.43 (1H, t, J = 5.6 Hz), 7.48 (1H, d, J = 8.4 Hz), 7.80 (1H, dd, J = 2.4, 8.4 Hz), 8.35 (1H, d, J = 2.4 Hz).
Reference: [1] Patent: WO2016/154241, 2016, A1, . Location in patent: Paragraph 578; 581
[2] Patent: EP1439175, 2004, A1, . Location in patent: Page 42-43
[3] Patent: WO2005/56529, 2005, A1, . Location in patent: Page/Page column 43
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  • [ 49608-01-7 ]
  • [ 182924-36-3 ]
Reference: [1] Patent: WO2016/154241, 2016, A1,
  • 6
  • [ 5326-23-8 ]
  • [ 64-17-5 ]
  • [ 49608-01-7 ]
Reference: [1] Patent: EP1180514, 2002, A1, . Location in patent: Example 113
[2] Tetrahedron, 2002, vol. 58, # 22, p. 4429 - 4438
[3] Journal of Medicinal Chemistry, 1993, vol. 36, # 18, p. 2676 - 2688
[4] Patent: US6344463, 2002, B1, . Location in patent: Page column 17
  • 7
  • [ 5326-23-8 ]
  • [ 78-39-7 ]
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Reference: [1] Patent: US5659042, 1997, A,
  • 8
  • [ 5326-23-8 ]
  • [ 49608-01-7 ]
Reference: [1] Patent: US5250548, 1993, A,
  • 9
  • [ 14906-63-9 ]
  • [ 1452-94-4 ]
  • [ 49608-01-7 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1988, vol. 36, p. 2244 - 2247
[2] Chemical and Pharmaceutical Bulletin, 1988, vol. 36, p. 2244 - 2247
  • 10
  • [ 2398-81-4 ]
  • [ 49608-01-7 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1988, vol. 36, p. 2244 - 2247
  • 11
  • [ 58757-38-3 ]
  • [ 64-17-5 ]
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Reference: [1] Chemical and Pharmaceutical Bulletin, 1988, vol. 36, p. 2244 - 2247
  • 12
  • [ 118292-06-1 ]
  • [ 49608-01-7 ]
  • [ 118292-40-3 ]
YieldReaction ConditionsOperation in experiment
60%
Stage #1: With potassium carbonate; triphenylphosphine In toluene at 45 - 50℃;
Stage #2: at 45 - 115℃;
Charged ethyl 6-chloronicotinate (10.0 gm) in a R.B. Flask arranged with reflux condenser on oil bath, containing toluene (100 ml). Stirred and charged potassium carbonate (30.0 gm), triphenylphosphine (4.0 gm) and 5percent Pd/C (4.0 gm) to the reaction solution. Gradually raised the temperature to 45-50 C and maintained under stirring at 45 - 50°C for 2 hours. Charged 6-ethynyl-4,4-dimethylthiochromane (8 gm) and Copper iodide (0.05 gm) at 45-50°C. After charging, the reaction temperature was raised to 105- 115°C and maintained under stirring at 105-1150C temperature for 10 hours. After completion, the reaction mass was cooled to 25-300C and filtered the catalyst Pd/C. To the filtrate charged water (300 ml) and stirred for 30 min. Separated the organic layer and the aqueous layer was extracted with toluene (100 ml). Separated the organic layer and combined all organic layers. Concentrated the solvent under reduced pressure to get residual mass. Charged hexane (25 ml) to the residual mass and stirred at 25-300C for 1.0 hour. Cooled the reaction to -10 to 5°C and maintained for 1.0 hour. Filtered the solid Tazarotene and dried in oven till constant weight. Weight of Tazarotene = 8.3 gm percent Yield = 60.0 percent.
9 g
Stage #1: With palladium on activated charcoal; potassium carbonate; sodium sulfate; triphenylphosphine In toluene at 50 - 55℃; for 2 h; Inert atmosphere
Stage #2: With copper(l) iodide In toluene at 105 - 115℃;
To 188 ml of toluene was added palladium on carbon (10 g) under N2 atmosphere. The mixture was heated to 105-115 °C to remove water by azeotropic distillation. Thereaction mass was cooled to 50-55 °C. To the above mixture, anhydrous sodium sulphate(12.5 g), anhydrous potassium carbonate (37.5 g), triphenylphosphine (5 g), ethyl 6-chioronicotinoate (12.5 g) and toluene (12.5 ml) were added at 50-55 °C and stirred for 2hours. To the above mixture, 4,4-dimethyl-6-ethynylthiochroman (10 g), cuprous iodide(0.06 g) and toluene (12.5 ml) were added and the reaction mixture was heated to 105-115 °C for 10-12 hours. The reaction mixture was cooled to 25-30 °C and water (125 ml)was added. The biphasi reaction mixture was filtered and from the filtrate, product enriched organic layer was separated. The organic layer was washed with water (2 X 65. ml) and brine solution (2 X 65 ml), dried over anhydrous sodium sulphate (5 g) and all the solvent was distilled off to get residual mass. The residual mass was dissolved in n20 heptane (50 ml) at 75-80 °C, which was treated with activated charcoal, neutral aluminaand filtered. The filtrate was stirred at 25-30 °C for 20 hours. The resulted solid was filtered off, washed with n-heptane (12.5 ml) and dried to yield 9 g of tazarotene. (HPLC purity of tazarotene— 97.64percent; Content of dimer impurity - 1.31percent).
Reference: [1] Patent: WO2009/116075, 2009, A2, . Location in patent: Page/Page column 12
[2] Patent: WO2015/107542, 2015, A2, . Location in patent: Page/Page column 12
[3] Patent: WO2015/107542, 2015, A3, . Location in patent: Page/Page column 12
  • 13
  • [ 118292-06-1 ]
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  • [ 118292-40-3 ]
Reference: [1] Patent: US5089509, 1992, A,
  • 14
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  • [ 588720-42-7 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 24, p. 8219 - 8248
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