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[ CAS No. 49843-98-3 ] {[proInfo.proName]}

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Cat. No.: {[proInfo.prAm]}
Chemical Structure| 49843-98-3
Chemical Structure| 49843-98-3
Structure of 49843-98-3 * Storage: {[proInfo.prStorage]}
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Quality Control of [ 49843-98-3 ]

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Product Details of [ 49843-98-3 ]

CAS No. :49843-98-3 MDL No. :MFCD03009471
Formula : C13H13ClN2O Boiling Point : -
Linear Structure Formula :- InChI Key :FUZYTVDVLBBXDL-UHFFFAOYSA-N
M.W : 248.71 Pubchem ID :5113032
Synonyms :
EX-527;SEN0014196;(±)-EX-527

Calculated chemistry of [ 49843-98-3 ]

Physicochemical Properties

Num. heavy atoms : 17
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.31
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 2.0
Molar Refractivity : 68.46
TPSA : 58.88 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.05 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.62
Log Po/w (XLOGP3) : 2.49
Log Po/w (WLOGP) : 2.73
Log Po/w (MLOGP) : 2.08
Log Po/w (SILICOS-IT) : 3.24
Consensus Log Po/w : 2.43

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.28
Solubility : 0.132 mg/ml ; 0.000529 mol/l
Class : Soluble
Log S (Ali) : -3.37
Solubility : 0.106 mg/ml ; 0.000425 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.37
Solubility : 0.0105 mg/ml ; 0.0000424 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.69

Safety of [ 49843-98-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H317-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 49843-98-3 ]

* 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 [ 49843-98-3 ]
  • Downstream synthetic route of [ 49843-98-3 ]

[ 49843-98-3 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 49844-36-2 ]
  • [ 49843-98-3 ]
YieldReaction ConditionsOperation in experiment
78% With ammonia In ethanol at 60 - 75℃; for 24.75 h; 2 (10 g, 40 mmole) was dissolved in ethanol (100 mL) 7M ammonia in ethanol (200 mL) was added and the material transferred to a Parr pressure reactor. The reaction vessel was purged briefly to displace any air with ammonia vapor. The reaction was then heated to 60° C. The reaction temperature overshot to 75° C. briefly then returned to 60° C. within 45 min. The material was stirred at this temperature for 24 hours. The reaction was then cooled to room temperature and the solvent removed in vacuo. This gave the crude product (9.6 gms) as an off-white foam. The material was chromatographed twice on a Biotage 40L column. The first chromatography, elution with 100percent ethyl acetate, failed to remove a trace impurity. A second chromatography utilizing a step gradient (starting with 1/1 heptane/ethyl acetate jumping to 1/4 heptane/ethyl acetate as the impurity began to elute) provided clean 4 (7.8 g, 31.4 mmole, 78percent) as an off-white crystalline solid. (7.8 g, 31.4 mmole, 78percent) as an off-white crystalline solid. 1H NMR δ (CD3OD, ppm) 7.34-7.38 (s, 1H), 7.20-7.24 (m, 1H), 6.95-7.03 (m, 1H), 3.69-3.75 (m, 1H), 2.59-2.75 (m, 2H), 1.76-2.20 (m, 4H).
45% With ammonia In methanol at 100℃; for 15 h; Step 3:
Ethyl 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxylate (1 g, 3.60 mmol, 1.00 equiv) (step 2) and NH3 (7M in MeOH) (15 mL) were added into a 30 mL pressure tank reactor (10 atm).
The resulting solution was stirred for 15 h at 100° C.
The resulting mixture was concentrated under vacuum.
The crude product was purified by Prep-HPLC with the following conditions: Column,)(Bridge Shield RP18 OBD Column, 5 μm, 19*150 mm; mobile phase, water (0.05percent TFA) and ACN (31.0percent ACN up to 42.0percent in 10 min); Detector, UV 254/220 nm.
This resulted in 400 mg (45percent) of 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide as a white solid.
1H NMR (400 MHz, DMSO-d6) δ: 10.81 (s, 1H), 7.44-7.36 (m, 2H), 7.29 (m, 1H), 7.10 (s, 1H), 7.00 (m, 1H), 3.66 (m, 1H), 2.64-2.56 (m, 2H), 2.11-1.89 (m, 3H), 1.70 (m, 1H). LC-MS: m/z=249 [M+H]+.
88.3 kg With ammonia In methanol at 0 - 50℃; for 51 h; Large scale Example 6: stage 3 procedure using pure ammoniaA solution of 6-chloro-2,3,4,9-tetrahydro-lH-carbazole-l-carboxylic acid ethyl ester (183 kg) in MeOH (850 1) in a pressure reactor was cooled to 5±5°C, and ammonia (328 kg) was added over 4 h while stirring at to 5±5°C. Then the temperature was increased to 45±5°C (4 bar internal pressure) and kept at this temperature for 47 h (HPLC check: no s.m. left).The solution was cooled to 0 - 10°C, filtered into a non-pressure reactor and warmed to 45±5°C over 4 h and kept at this temperature for another 12 h to gas off the excess ammonia. After charcoal treatment (8 kg) at 60°C, filtration, washing with MeOH (150 1) and evaporation of solvent (300 1), water (200 1) is added and the mixture is cooled to 3±3°C to precipitate 6-chloro-2,3,4,9-tetrahydro-lH-carbazole-l -carboxylic acid amide product. The solid is centrifuged and drummed off for the subsequent recrystallisation. Yield: 142 kg. With a LOD = 16percent this corresponds to 1 19 kg dry material (81.3percent of theory).This material, dissolved in in methyethyl ketone (407 kg) is heated to reflux, and cyclohexane is added at to 68 -77°C over 15 min. The mixture is stirred at to 68°C for 1.5h, then it is cooled to 0°C over 2h. The solid is isolated by centrifugation (146 kg, wet).The solid is suspended in 2-propanol heated to reflux within 2h 20 min(complete dissolution), then cooled to 0±5°C over 2.5h and kept at to 0±5°C for lh. The solid is centrifuged and then dried for 18 in a paddle dryer (to 20 - 49°C, 28 - 86 mbar) to give the final product (88.3 kg).
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
[2] Patent: US2005/256181, 2005, A1, . Location in patent: Page/Page column 20
[3] Patent: US2017/190664, 2017, A1, . Location in patent: Paragraph 0237; 0242-0243
[4] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
[5] Patent: WO2013/57258, 2013, A1, . Location in patent: Page/Page column 13
  • 2
  • [ 871586-78-6 ]
  • [ 49843-98-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
  • 3
  • [ 1655-07-8 ]
  • [ 49843-98-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
[2] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
[3] Patent: WO2013/57258, 2013, A1,
[4] Patent: US2017/190664, 2017, A1,
[5] Patent: US2005/256181, 2005, A1,
  • 4
  • [ 30132-23-1 ]
  • [ 49843-98-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
[2] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
[3] Patent: US2017/190664, 2017, A1,
[4] Patent: US2005/256181, 2005, A1,
  • 5
  • [ 50639-66-2 ]
  • [ 49843-98-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 25, p. 8045 - 8054
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