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[ CAS No. 37687-57-3 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 37687-57-3
Chemical Structure| 37687-57-3
Chemical Structure| 37687-57-3
Structure of 37687-57-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 37687-57-3 ]

CAS No. :37687-57-3 MDL No. :MFCD03425852
Formula : C8H7ClO3 Boiling Point : -
Linear Structure Formula :- InChI Key :DTMJGFBJQBQOIA-UHFFFAOYSA-N
M.W : 186.59 Pubchem ID :603956
Synonyms :

Calculated chemistry of [ 37687-57-3 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 45.35
TPSA : 46.53 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) : -6.41 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.68
Log Po/w (XLOGP3) : 1.45
Log Po/w (WLOGP) : 1.87
Log Po/w (MLOGP) : 1.09
Log Po/w (SILICOS-IT) : 2.14
Consensus Log Po/w : 1.65

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.15
Solubility : 1.33 mg/ml ; 0.00711 mol/l
Class : Soluble
Log S (Ali) : -2.03
Solubility : 1.73 mg/ml ; 0.00927 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.52
Solubility : 0.569 mg/ml ; 0.00305 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.5

Safety of [ 37687-57-3 ]

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 [ 37687-57-3 ]

* 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 [ 37687-57-3 ]
  • Downstream synthetic route of [ 37687-57-3 ]

[ 37687-57-3 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 37687-57-3 ]
  • [ 67287-53-0 ]
Reference: [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
[2] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
[3] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
  • 2
  • [ 37687-57-3 ]
  • [ 74-88-4 ]
  • [ 5417-17-4 ]
YieldReaction ConditionsOperation in experiment
92% With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide In dichloromethane at 20℃; for 12 h; General procedure: Following an adaptation of the procedure of McKillop et al.7, anaqueous solution of 1.20 g of NaOH (30 mmol, 3.0 eq.) in 50 mL of deionized water was added to astirring solution of 2.31 g (10 mmol) of 2-bromo-isovanillin (2-bromo-3-hydroxy-4-methoxybenzaldehyde)in 50 mL of dichloromethane. Next, phase transfer catalyst was added, as 3.40 g of eithertetrabutylammonium hydrogen sulfate (TBAHS, 10.0 mmol, 1.0 eq.) or recycled catalyst (assuming thatthe recovered catalyst is tetrabutylammonium hydroxide, 2.6 g is 10 mmol, 1.0 eq). Once dissolved, 17g (120 mmol, 12 eq.) of methyl iodide was then added to the mixture and the reaction was allowed tostir at room temperature. Reaction progress was monitored by HPLC. As monitored by HPLC, reactionprogress generally showed complete turnover to product with no side products by 3 hours, however thesolution was typically allowed to stir overnight for convenience. The reaction mixture was extracted with3 x 50 mL portions of CH2Cl2. The combined organic extracts were washed with brine and deionizedwater, dried over MgSO4, filtered, and concentrated by evaporation under reduced pressure to yield aeither a white or yellow solid. To remove catalyst, the solid was first ground to a fine powder with amortar and pestle. This solid was poured on top of a 2 – 3 cm layer of dry silica gel in a 3 – 4 cm (I.D.)sintered glass fritted Buchner funnel. The solid was extracted with 1:5 ethyl acetate:hexanes in 75 mLportions by pouring the solvent mixture over the dry solids with vacuum suction to collect the solutionin a round bottom flask. Allow the solids to dry between solvent portions for best separation. The first1250 mL typically contained 85 - 95percent of pure product. The combined eluent was evaporated to drynessunder reduced pressure to afford a dense, white, flakey solid (2.06 g, 90percent). If the product was found tocontain non-halogenated contaminants from the previous step, pure halogenated product was easilyobtained by recrystallization from hexanes. The phase transfer catalyst, presumably a mixture oftetrabutylammonium salts, was recovered by either scooping it out of the filter or by eluting with ethylacetate.
42 mmol, 98% With potassium carbonate In acetonitrile Step 2--Formation of 2-Chloro-3,4-dimethoxybenzaldehyde
To 8.03 g (43 mmol) of 2-Chloro-3-hydroxy-4-methoxybenzaldehyde in 100 mL of acetonitrile was added 7.7 g (55 mmol) of powdered potassium carbonate followed by 8.3 mL (0.13 mol) of iodomethane.
The reaction was slowly warmed to reflux where it was stirred for 24 h.
After cooling to room temperature the suspension was filtered and the filtrate evaporated to dryness in vacuo to give 8.5 g (42 mmol, 98percent) of a white solid shown to be desired product by 1 H NMR.
Reference: [1] Synlett, 2014, vol. 25, # 20, p. 2891 - 2894
[2] Patent: US5866513, 1999, A,
  • 3
  • [ 37687-57-3 ]
  • [ 584-08-7 ]
  • [ 5417-17-4 ]
YieldReaction ConditionsOperation in experiment
96% With sodium hydroxide In chloroform; water; acetonitrile Step 2
Synthesis of 2-chloro-3,4-dimethoxybenzaldehyde
184 g (0.986 mol) of 2-chloro-3-hydroxy-4-methoxybenzaldehyde was dissolved in 2 l of CH3 CN. 204 g (1.476 mol) of K2 CO3 and 298 g (2.096 mol) of CH3 I were added to the solution, which was heated under reflux for 4 hours.
After cooling, the crystals were separated by filtration and the mother liquor was concentrated under reduced pressure.
800 ml of water and 600 ml of CHCl3 were added to the residue to conduct extraction.
The CHCl3 layer was washed with 500 ml of 10percent NaOH and a saturated Nacl aqueous solution.
It was dehydrated over MgSO4 and concentrated to dryness under reduced pressure to obtain 189.49 g (96percent) of 2-chloro-3,4-dimethoxybenzaldehyde.
mp 70°~72° C.
NMR (90 MHz, CDCl3) δ:3.88 (3H, s), 3.96 (3H, s), 6.92 (1H, d), 7.72 (1H, d), 10.28 (1H, s)
Reference: [1] Patent: US5292521, 1994, A,
  • 4
  • [ 37687-57-3 ]
  • [ 77-78-1 ]
  • [ 5417-17-4 ]
Reference: [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
  • 5
  • [ 621-59-0 ]
  • [ 37687-57-3 ]
  • [ 5417-17-4 ]
Reference: [1] Patent: US4104379, 1978, A,
  • 6
  • [ 621-59-0 ]
  • [ 37687-57-3 ]
YieldReaction ConditionsOperation in experiment
80% With sulfuryl dichloride In acetic acid at 0 - 2℃; for 2 h; Neat sulfuryl chloride (14.85 g, 110mmol, 1.1 eq.) was added dropwise over 5 minutes to a solution of isovanillin (15.00 g, 100 mmol, 1 eq)in 120 mL of glacial acetic acid in an ice-water bath. After 2 hours of stirring with ice-water bath cooling,the reaction was filtered, washed with cold acetic acid, and dried under vacuum to afford 14.16 g ofwhite solid. HPLC and 1H-NMR indicate indicated the presence of unreacted isovanillin. This solid wasdissolved in boiling ethanol and recrystallized to yield 11.91 g (80percent) of fluffy white needles (mp = 200.0– 209.9 °C). 1H-NMR indicated <1percent isovanillin after one recrystallization. 1H NMR (300 MHz, CDCl3): 10.19 (s, 1H, CHO), 9.83 (d, J = 31.4 Hz, 1H, OH), 7.41 (d, J = 8.6 Hz, 1H, ArH), 7.12 (d, J = 8.6 Hz, 1H, ArH),3.93 (s, 3H, OCH3); 1H-NMR (300 MHz, DMSO-d6): 10.19 (s, 1H, CHO), 9.89 (s, 1H, OH), 7.42 (d, J = 8.6Hz, 1H, Ar-H), 7.12 (d, J = 8.6 Hz, 1H, Ar-H), 3.93 (s, 3H, OMe); EI-MS m/z: 187 (M+2), 185 (M+, 100percent),171, 157, 143, 129, 115, 107, 99, 79, 65, 51. UV-Vis: 215.3, 237.2, 283.8 nm.
69% With tert-butylhypochlorite In acetic acid Step 1
Synthesis of 2-chloro-3-hydroxy-4-methoxybenzaldehyde
41.2 g (0.271 mol) of isovanillin was dissolved in 160 ml of 90percent AcOH under heating.
29.41 g of t-BuOCl was added dropwise to the solution while it was kept at 35° to 40° C.
The solution was stirred at room temperature for 3 hours and then 200 ml of ether was added thereto.
The mixture was left to stand overnight and crystals thus formed were separated by filtration and washed with ether.
42.0 g of the crude crystals were recrystallized from acetonitrile to obtain 35 g of 2-chloro-3-hydroxy-4-methoxybenzaldehyde (69percent).
mp 203°~205° C.
NMR (90 MHz, DMSO-d6) δ:3.94 (3H, s), 7.10 (1H, d), 7.42 (1H, d), 9.84 (1H, s), 10.16 (1H, s)
Reference: [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
[2] Organic Process Research and Development, 2001, vol. 5, # 1, p. 45 - 49
[3] Synlett, 2014, vol. 25, # 20, p. 2891 - 2894
[4] Journal of Organic Chemistry, 2012, vol. 77, # 2, p. 977 - 984
[5] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 6, p. 1805 - 1814
[6] Turkish Journal of Chemistry, 2010, vol. 34, # 2, p. 181 - 186
[7] Patent: US5292521, 1994, A,
[8] Angewandte Chemie - International Edition, 1998, vol. 37, # 9, p. 1236 - 1239
[9] Yakugaku Zasshi, 1956, vol. 76, p. 1122,1125[10] Chem.Abstr., 1957, p. 3505
[11] Arzneimittel-Forschung/Drug Research, 1986, vol. 36, # 3, p. 457 - 460
[12] Patent: US5866513, 1999, A,
  • 7
  • [ 5417-17-4 ]
  • [ 37687-57-3 ]
Reference: [1] Journal of the American Chemical Society, 1955, vol. 77, p. 5314,5317
  • 8
  • [ 93983-14-3 ]
  • [ 37687-57-3 ]
Reference: [1] Journal of the American Chemical Society, 1955, vol. 77, p. 5314,5317
  • 9
  • [ 90282-99-8 ]
  • [ 37687-57-3 ]
Reference: [1] Journal of the American Chemical Society, 1955, vol. 77, p. 5314,5317
  • 10
  • [ 37687-57-3 ]
  • [ 71636-38-9 ]
Reference: [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
[2] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
[3] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
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