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[ CAS No. 21512-16-3 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 21512-16-3
Chemical Structure| 21512-16-3
Chemical Structure| 21512-16-3
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Product Details of [ 21512-16-3 ]

CAS No. :21512-16-3 MDL No. :MFCD09037804
Formula : C6H3NOS Boiling Point : -
Linear Structure Formula :- InChI Key :PZIFYWVUYHMYOA-UHFFFAOYSA-N
M.W : 137.16 Pubchem ID :12280004
Synonyms :

Calculated chemistry of [ 21512-16-3 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 34.42
TPSA : 69.1 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) : -6.11 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.32
Log Po/w (XLOGP3) : 1.45
Log Po/w (WLOGP) : 1.43
Log Po/w (MLOGP) : -0.27
Log Po/w (SILICOS-IT) : 2.62
Consensus Log Po/w : 1.31

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.95
Solubility : 1.54 mg/ml ; 0.0112 mol/l
Class : Very soluble
Log S (Ali) : -2.51
Solubility : 0.427 mg/ml ; 0.00311 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.67
Solubility : 2.93 mg/ml ; 0.0213 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.25

Safety of [ 21512-16-3 ]

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

Application In Synthesis of [ 21512-16-3 ]

* 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 [ 21512-16-3 ]
  • Downstream synthetic route of [ 21512-16-3 ]

[ 21512-16-3 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 1003-31-2 ]
  • [ 68-12-2 ]
  • [ 21512-16-3 ]
YieldReaction ConditionsOperation in experiment
76%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran at -70℃; for 1 h; Inert atmosphere
Stage #2: at -78 - -70℃; for 1.5 h; Inert atmosphere
Stage #3: With water; citric acid In tetrahydrofuran
Method C5- Formylthiophene-2-carbonitrile (Intermediate compound)Under inert atmosphere BuLi (1 1 .7 ml, 29.3 mmol, 2.5 M) was added to a mixture of diisopropylamine (4.1 ml, 29.3 mmol) and THF (150 ml) at below - 70°C. When addition was finished, the mixture was allowed to reach room- temperature. The mixture was cooled back to -70°C again, where 2- thiophenecarbonitrile (3.0 g, 26.7 mmol), solved in THF (15 ml) was added drop- wise and stirred an additional hour. At -78°C. DMF (8.2 ml, 106.6 mmol) was added below -70°C. The mixture was stirred for 1 .5 h at -78°C. Citric acid (10 g) was added to the reaction-mixture. The reaction-mixture was poured out on water. The aqueous phase was extracted with diethylether. The product was dried and evaporated. The reaction mixture was purified by silica gel column chromatography using 10-50percent heptane/EtOAc as solvent. The product was isolated as a solid. Yield 2.8 g (76percent).
Reference: [1] Patent: WO2011/73298, 2011, A1, . Location in patent: Page/Page column 18
[2] Patent: US2008/200535, 2008, A1, . Location in patent: Page/Page column 169
  • 2
  • [ 1003-31-2 ]
  • [ 21512-16-3 ]
YieldReaction ConditionsOperation in experiment
84% With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate EXAMPLE 65 STR100 A) Preparation of 2-cyano-5-formylthiophene
To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere.
The flask was cooled to an internal temperature of -78° C. (dry ice/acetone).
To this stirring solution was added n-butyllithium (1.6 M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min.
To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min.
The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe.
This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL).
Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each).
Layers were separated and the aqueous phase was washed once with diethyl ether.
The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes).
Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
84% With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate EXAMPLE 65 STR95 A) Preparation of 2-cyano-5-formylthiophene
To a flame-dried 3 neck 1L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere.
The flask was cooled to an internal temperature of -78° C. (dry ice/acetone).
To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min.
To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min.
The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe.
This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL).
Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each).
Layers were separated and the aqueous phase was washed once with diethyl ether.
The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes).
Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
84% With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate A)
Preparation of 2-cyano-5-formylthiophene
To a flame-dried 3 neck 1L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere.
The flask was cooled to an internal temperature of -78° C. (dry ice/acetone).
To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min.
To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min.
The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe.
This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL).
Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each).
Layers were separated and the aqueous phase was washed once with diethyl ether.
The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes).
Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
84% With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate EXAMPLE 65 STR106 A) Preparation of 2-cyano-5-formylthiophene
To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere.
The flask was cooled to an internal temperature of -78° C. (dry ice/acetone).
To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min.
To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min.
The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe.
This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL).
Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each).
Layers were separated and the aqueous phase was washed once with diethyl ether.
The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes).
Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
50 %Chromat.
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.75 h;
Stage #2: With N,N-dimethyl-formamide; methylbutenedioic acid In water at -78℃; for 20 h;
A solution of diisopropylamine (35.3 ml, 0.251 moles) in tetrahydrofuran (500 ml) was cooled to -78 C. under a nitrogen blanket. To this was added 1.6M n-butyllithium in hexanes (157 ml, 0.251 moles) and allowed to stir for 5 min. Then slowly added thiopene-2-carbonitrile (21.33 ml, 0.229 moles) in tetrahydrofuran (115 ml) and allowed to stir. After 45 min. was added NN-dimethylformamide (88.66 ml, 1.145 moles) at -78 C. Citric acid (40 g) was added after 2 h. followed by water (240 ml) and stirred for 18 h. The reaction was concentrated in vacuo, transferred to a separatory funnel, diluted with brine, and extracted twice with ether. The combined ether layers were washed with brine, dried over magnesium sulfate, filtered, and the solvent removed in vacuo. Chromatography yielded 15.8 g (50percent) of 2-cyano-5-formylthiophene (EX-55A) as a brown solid: 1H NMR (300 MHZ, CDCl3) d 10.02 (s, 1H), 7.79 (m, 1H), 7.30 (m, 1H).

Reference: [1] Patent: US5914319, 1999, A,
[2] Patent: US5707966, 1998, A,
[3] Patent: US5710130, 1998, A,
[4] Patent: US5726159, 1998, A,
[5] Patent: US5705487, 1998, A,
[6] Patent: US6664255, 2003, B1, . Location in patent: Page column 117
  • 3
  • [ 72835-25-7 ]
  • [ 21512-16-3 ]
Reference: [1] Patent: US5053415, 1991, A,
[2] Journal of Organic Chemistry, 1957, vol. 22, p. 1636,1640
  • 4
  • [ 72835-25-7 ]
  • [ 134135-41-4 ]
  • [ 21512-16-3 ]
Reference: [1] Patent: US5135937, 1992, A,
  • 5
  • [ 90924-79-1 ]
  • [ 21512-16-3 ]
Reference: [1] Journal of Organic Chemistry, 1957, vol. 22, p. 1636,1640
  • 6
  • [ 16494-36-3 ]
  • [ 21512-16-3 ]
Reference: [1] Journal of Organic Chemistry, 1957, vol. 22, p. 1636,1640
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