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[ CAS No. 844442-38-2 ] {[proInfo.proName]}

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Chemical Structure| 844442-38-2
Chemical Structure| 844442-38-2
Structure of 844442-38-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 844442-38-2 ]

CAS No. :844442-38-2 MDL No. :MFCD13184820
Formula : C16H17Cl2N5O2 Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W : 382.24 Pubchem ID :-
Synonyms :
AT7519M

Calculated chemistry of [ 844442-38-2 ]

Physicochemical Properties

Num. heavy atoms : 25
Num. arom. heavy atoms : 11
Fraction Csp3 : 0.31
Num. rotatable bonds : 6
Num. H-bond acceptors : 4.0
Num. H-bond donors : 4.0
Molar Refractivity : 99.65
TPSA : 98.91 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.79 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.2
Log Po/w (XLOGP3) : 2.59
Log Po/w (WLOGP) : 1.88
Log Po/w (MLOGP) : 1.68
Log Po/w (SILICOS-IT) : 2.71
Consensus Log Po/w : 2.21

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.77
Solubility : 0.0647 mg/ml ; 0.000169 mol/l
Class : Soluble
Log S (Ali) : -4.32
Solubility : 0.0185 mg/ml ; 0.0000483 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -6.13
Solubility : 0.000283 mg/ml ; 0.00000074 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.63

Safety of [ 844442-38-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H320-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 844442-38-2 ]

* 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.

  • Downstream synthetic route of [ 844442-38-2 ]

[ 844442-38-2 ] Synthesis Path-Downstream   1~36

  • 1
  • [ 844443-90-9 ]
  • [ 844442-38-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In ethyl acetate; at 20.0℃; for 1.0h; A product of Procedure B containing a piperidine group bearing an N-fe/f-butoxycarbonyl (t-Boc) protecting group (40 mg) was treated with saturated ethyl acetate/HCI, and stirred at room temperature for 1 hour. A solid precipitated out of the reaction mixture, which was filtered off, washed with ether, and then dried to give 25 mg product (LC/MS: [M+Hf 364).
With hydrogenchloride; In ethyl acetate; at 20.0℃; for 1.0h; Deprotection of Piperidine Ring Nitrogen by Removal of tert- Butoxycarbonyl GroupA product of Procedure B containing a piperidine group bearing an N-tert-butoxycarbonyl (t-Boc) protecting group (40 mg) was treated with saturated ethyl acetate/HCI, and stirred at room temperature for 1 hour. A solid precipitated out of the reaction mixture, which was filtered off, washed with ether, and then dried to give 25 mg product (LC/MS: [M+H]+ 364).
With hydrogenchloride; ethyl acetate; In methanol; ethyl acetate; at 20.0℃; A solution of 4-[4-(2,7-dichloro-benzoylamino)-1H-pyrazole-3-carbonyl]-amino}- piperidine-I-carboxylic acid tert-butyl ester (7.9 g) in MEOH (50 mL) and EtOAc (50ML) was treated with sat. HCL-ETOAC (40 mL) then stirred at r. t. overnight. The product did not crystallise due to the presence of methanol, and therefore the reaction mixture was evaporated and the residue triturated with EtOAc. The resulting off white solid was collected by filtration, washed with EtOAc and sucked dry on the sinter to give 6.3g OF 4-(2, 6-DICHLORO-BENZOYLAMINO)-LH-PYRAZOLE-3- carboxylic acid piperidin-4-ylamide as the hydrochloride salt. (LC/MS: Rt 5.89, [M+H] + 382/384).
With hydrogenchloride; In ethyl acetate; at 20.0℃; for 1.0h;Product distribution / selectivity; A product of Procedure A containing a piperidine group bearing an N-terf-butoxycarbonyl (t-Boc) protecting group (40 mg) was treated with saturated ethyl acetate/HCI, and stirred at room temperature for 1 hour. A solid precipitated out of the reaction mixture, which was filtered off, washed with ether, and then dried to give 25 mg product (LC/MS: [M+H]+ 364).
2.55 kg With trifluoroacetic acid; In dichloromethane;Large scale; Adding 42.11 kg of dichloromethane to the 100 L reactor, 2.8 kg of intermediate 3, stirring, adding trifluoroacetic acid (6.86 kg) to the reaction droplets, dropping, and stirring for 3-5 hours;The reaction solution was concentrated to dryness under reduced pressure. isopropyl alcohol (11 kg) was added to the residue, filtered, and the filter cake was rinsed with isopropyl alcohol (1 kg).The filter cake is dried, and anhydrous ethanol (6.5 kg) is added to the crude product, and the temperature is lowered to 40 to 45 C after the temperature is dissolved.The solvent was concentrated under reduced pressure to remove about half of the solvent, and the mixture was cooled to 20 to 25 C, filtered, and the filter cake was rinsed with anhydrous ethanol (0.5 kg) to obtain 2.55 kg of intermediate 4

  • 2
  • [ 844442-38-2 ]
  • [ 75-75-2 ]
  • 4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-yl-amide methanesulphonic salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; water; at 20.0℃; for 14.0h;Product distribution / selectivity; The hydrochloride salt was taken up in MeOH and passed through a Strata-NH2 column, eluting with MeOH. The product-containing fractions were reduced in vacuo to give 4-(2,6-dichlorobenzoylamino)-lH-pyrazole-3-carboxylic acid piperidin-4-ylamide free base. To a mixture of the free base in MeOH was added MsOH (70% in water) and the mixture was stirred at ambient for 14 hours, then reduced in vacuo, azeotroping with toluene (x 3). The residue was purified by trituration with acetone and dried in the vacuum oven to give the mesylate salt.
  • 3
  • [ 844442-38-2 ]
  • [ 64-19-7 ]
  • 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-yl-amide acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; at 20.0℃; for 1.0h; To a stirred suspension of 4-(2,6-dichloro-benzoylamino)-lH-pyrazole-3-carboxylic acid piperidin-4-ylamide (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6-dichloro-benzoylamino)-lH-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.1H NMR (400 MHz, DMSO-J6) delta 10.20 (s, IH), 8.40 (d, IH), 8.35 (s, IH), 7.60 - 7.50 (m, 3H), 3.85 (m, IH), 3.00 (d, 2H), 2.60 (t, 2H), 1.85 (s, 3H), 1.70 (d, 2H), 1.55 (m, 2H)
In methanol; at 20.0℃; for 1.0h; To a stirred suspension of <strong>[844442-38-2]4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide</strong> (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6- dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.1H NMR (400 MHz, DMSO-d6) D 10.20 (s, 1 H), 8.40 (d, 1 H), 8.35 (s, 1 H), 7.60 - 7.50 (m, 3H), 3.85 (m, 1 H), 3.00 (d, 2H), 2.60 (t, 2H), 1.85 (s, 3H), 1.70 (d, 2H), 1.55 (m, 2H) To a stirred suspension of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxyIic acid piperidin-4-ylamide (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6- dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.1H NMR (400 MHz, DMSO-d6) delta 10.20 (s, 1H), 8.40 (d, 1H), 8.35 (s, 1H), 7.60-7.50 (m, 3H), 3.85 (m, 1H), 3.00 (d, 2H), 2.60 (t, 2H), 1.85 (s, 3H), 1.70 (d, 2H), 1.55 (m, 2H)
In methanol; at 20.0℃; for 1.0h; To a stirred suspension of <strong>[844442-38-2]4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide</strong> (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6- dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.1H NMR (400 MHz, DMSO-d6) D 10.20 (s, 1 H), 8.40 (d, 1 H), 8.35 (s, 1 H), 7.60 - 7.50 (m, 3H), 3.85 (m, 1 H), 3.00 (d, 2H), 2.60 (t, 2H), 1.85 (s, 3H), 1.70 (d, 2H), 1.55 (m, 2H) To a stirred suspension of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxyIic acid piperidin-4-ylamide (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6- dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.1H NMR (400 MHz, DMSO-d6) delta 10.20 (s, 1H), 8.40 (d, 1H), 8.35 (s, 1H), 7.60-7.50 (m, 3H), 3.85 (m, 1H), 3.00 (d, 2H), 2.60 (t, 2H), 1.85 (s, 3H), 1.70 (d, 2H), 1.55 (m, 2H)
In methanol; at 20.0℃; for 1.0h; To a stirred suspension of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with <n="333"/>acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6-dichloro-benzoylamino)- 1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.1H NMR (400 MHz, DMSO-Cf6) delta 10.20 (s, 1H), 8.40 (d, 1H), 8.35 (s, 1H), 7.60 - 7.50 (m, 3H), 3.85 (m, 1 H), 3.00 (d, 2H), 2.60 (t, 2H), 1.85 (s, 3H), 1.70 (d, 2H), 1.55 (m, 2H)
In methanol; at 20.0℃; for 1.0h; To a solution of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4- ylamide hydrochloride salt (Example 2C) 20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro-benzoylamino)-1 H- pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-Cf6) delta 10.20 (s, 1H), 8.30 (s, 1H), 8.25 (d, 1 H), 7.60 - 7.50 (m, 3H), 3.70 (m, 1 H), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H).To a stirred suspension of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6-dichloro-benzoylamino)- 1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.
In methanol; at 20.0℃; for 1.0h; To a stirred suspension of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with <n="85"/>acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6-dichloro-benzoylamino)- 1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.1H NMR (400 MHz, DMSO-cfe) delta 10.20 (s, 1H), 8.40 (d, 1 H), 8.35 (s, 1H), 7.60 - 7.50 (m, 3H), 3.85 (m, 1 H), 3.00 (d, 2H), 2.60 (t, 2H), 1.85 (s, 3H), 1.70 (d, 2H)1 1.55 (m, 2H)

  • 4
  • AT7519 [ No CAS ]
  • [ 844442-38-2 ]
YieldReaction ConditionsOperation in experiment
In methanol;Strata-NH2;Product distribution / selectivity; The hydrochloride salt was taken up in MeOH and passed through a Strata-NH2 column, eluting with MeOH. The product-containing fractions were reduced in vacuo to give 4-(2,6-dichlorobenzoylamino)-lH-pyrazole-3-carboxylic acid piperidin-4-ylamide free base. To a mixture of the free base in MeOH was added MsOH (70% in water) and the mixture was stirred at ambient for 14 hours, then reduced in vacuo, azeotroping with toluene (x 3). The residue was purified by trituration with acetone and dried in the vacuum oven to give the mesylate salt.
With sodium hydrogencarbonate; In water; at 20.0℃; for 1.0h;Product distribution / selectivity; EXAMPLE 8Preparation of 4-f2.6-dichloro-benzoylamino)-lH-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt EPO <DP n="96"/>To a solution of 4-(2,6-dichloro-benzoylamino)-lH-pyrazole-3-carboxylic acid piperidin-4-ylamide hydrochloride salt (20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4- (2,6-dichloro-benzoylamino)-lH-pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-J6) delta 10.20 (s, IH), 8.30 (s, IH), 8.25 (d, IH), 7.60 - 7.50 (m, 3H), 3.70 (m, IH), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H).
With sodium hydrogencarbonate; In water; at 20.0℃; for 1.0h; To a solution of 4-(2,6-dichloro-benzoyIamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide hydrochloride salt (Example (237C) 20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro- benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-d6) D 10.20 (s, 1 H), 8.30 (s, 1 H), 8.25 (d, 1 H), 7.60 - 7.50 (m, 3H), 3.70 (m, 1 H), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H). To a solution of 4-(2,6-dichIoro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide hydrochloride salt (20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro-benzoylamino)-1H- pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-d6) delta 10.20 (s, 1H), 8.30 (s, 1H), 8.25 (d, 1H), 7.60-7.50 (m, 3H), 3.70 (m, 1H), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H).
With sodium hydrogencarbonate; In water; at 20.0℃; for 1.0h; To a solution of 4-(2,6-dichloro-benzoyIamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide hydrochloride salt (Example (237C) 20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro- benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-d6) D 10.20 (s, 1 H), 8.30 (s, 1 H), 8.25 (d, 1 H), 7.60 - 7.50 (m, 3H), 3.70 (m, 1 H), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H). To a solution of 4-(2,6-dichIoro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide hydrochloride salt (20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro-benzoylamino)-1H- pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-d6) delta 10.20 (s, 1H), 8.30 (s, 1H), 8.25 (d, 1H), 7.60-7.50 (m, 3H), 3.70 (m, 1H), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H).
With sodium hydrogencarbonate; In water; for 1.0h; To a solution of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4- ylamide hydrochloride salt (Example 2C) 20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro-benzoylamino)-1H- pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-d6) delta 10.20 (s, 1 H), 8.30 (s, 1 H), 8.25 (d, 1 H), 7.60 - 7.50 (m, 3H), 3.70 (m, 1 H), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H).
With sodium hydrogencarbonate; In water; at 20.0℃; for 1.0h; To a solution of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4- ylamide hydrochloride salt (Example 2C) 20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro-benzoylamino)-1 H- pyrazole-3-carboxylic acid piperidin-4-ylamide.1H NMR (400 MHz, DMSO-Cf6) delta 10.20 (s, 1H), 8.30 (s, 1H), 8.25 (d, 1 H), 7.60 - 7.50 (m, 3H), 3.70 (m, 1 H), 3.00 (d, 2H), 2.50 (m, 2H), 1.70 (d, 2H), 1.50 (m, 2H).To a stirred suspension of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide (10.0 g, 26.2 mmol) in methanol (150 ml) was added glacial acetic acid (15 ml, 262 mmol) at ambient temperature. After 1 h, a clear solution was obtained which was reduced in vacuo azeotroping with toluene (x 2). The residue was then triturated with acetonitrile (2 x 100 ml) and the solid dried in vacuo to give 4-(2,6-dichloro-benzoylamino)- 1 H-pyrazole-3-carboxylic acid piperidin-4-ylamide acetic acid salt (10.3 g) as a white solid.
With sodium hydrogencarbonate; In water; at 20.0℃; for 1.0h;Product distribution / selectivity; To a solution of 4-(2,6-dichloro-benzoylamino)-1 H-pyrazole-3-carboxylic acid piperidin-4- ylamide hydrochloride salt (Example 2C) 20.6 g, 50 mmol) in water (500 ml) stirring at ambient temperature was added sodium bicarbonate (4.5 g, 53.5 mmol). The mixture was stirred for 1 hour and the solid formed collected by filtration and dried in vacuo azeotroping with toluene (x 3) to give the corresponding free base of 4-(2,6-dichloro-benzoylamino)-1 H- pyrazole-3-carboxylic acid piperidin-4-ylamide.

  • 5
  • 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-yl-amide acetate [ No CAS ]
  • [ 844442-38-2 ]
  • [ 64-19-7 ]
YieldReaction ConditionsOperation in experiment
at 231.5℃; The acetate salt has been analysed by DSC and exhibits a peak at 231.50 0C due to the loss of acetic acid and a further peak at 292.88 0C due to the decomposition of the compound. The absence of peaks at lower temperatures indicates that the acetate salt is anhydrous.
  • 7
  • [ 844443-90-9 ]
  • HCl-EtOAc [ No CAS ]
  • [ 844442-38-2 ]
YieldReaction ConditionsOperation in experiment
In methanol; ethyl acetate; A solution of 4-[4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (7.9 g) in MeOH (50 mL) and EtOAc (50 ml) was treated with sat. HCl-EtOAc (40 mL) then stirred at r.t. overnight. The product did not crystallise due to the presence of methanol, and therefore the reaction mixture was evaporated and the residue triturated with EtOAc. The resulting off white solid was collected by filtration, washed with EtOAc and sucked dry on the sinter to give 6.3 g of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide as the hydrochloride salt. (LC/MS: R. 5.89, [M+H]+ 382/384).
  • 8
  • [ 844443-90-9 ]
  • HCl-EtOAc [ No CAS ]
  • [ 844442-38-2 ]
  • AT7519 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; ethyl acetate; 2C. 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid Piperidin-4-ylamide A solution of 4-[4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (7.9 g) in MeOH (50 mL) and EtOAc (50 ml) was treated with sat. HCl-EtOAc (40 mL) then stirred at r.t. overnight. The product did not crystallise due to the presence of methanol, and therefore the reaction mixture was evaporated and the residue triturated with EtOAc. The resulting off white solid was collected by filtration, washed with EtOAc and sucked dry on the sinter to give 6.3 g of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide as the hydrochloride salt. (LC/MS: Rt 5.89, [M+H]+ 382/384).
  • 9
  • [ 123-91-1 ]
  • [ 844443-90-9 ]
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-yl-amide methanesulphonic salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
With methanesulfonic acid; Preparation of 4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide methanesuldhonate 4-[4-(2,6-Dichlorobenzoylamino)-1H-pyrazole-3-carbonyl]amino}-piperidine-1-carboxylic acid tert-butyl ester (0.561 Kg, 1.16 Mol, 1.0 wt) and 1,4-dioxane (14.00 L, 26.0 vol) were stirred under nitrogen and heated to 80 to 90 C. Methanesulphonic acid (0.30 L, 4.62 Mol, 0.54 vol) was added over 30 to 60 minutes at 80 to 90 C. and the contents heated to and maintained at 95 to 105 C. for 1 to 24 hours. Reaction completion was determined by 1H NMR analysis. The reaction mixture was cooled to 20 to 30 C. and the resulting precipitate collected by filtration. The filter-cake was washed with propan-2-ol (2*1.10 L, 2*2.0 vol) and pulled dry on the filter for 3 to 24 hours to give 4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide methanesulphonate [0.558 Kg, 100.2% th, 99.4% w/w, 1H NMR (d6-DMSO) concordant with structure, 98.13% by HPLC area] as an off-white solid.
  • 10
  • [ 87120-72-7 ]
  • [ 844442-38-2 ]
  • 11
  • [ 844443-80-7 ]
  • [ 844442-38-2 ]
  • 12
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)butanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 13
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(4-((4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)amino)-4-oxobutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 14
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)hexanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 15
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(4-((6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)amino)-4-oxobutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 16
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(4-((2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)amino)-4-oxobutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 17
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(4-((2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)ethyl)amino)-4-oxobutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 18
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(4-((4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)butyl)amino)-4-oxobutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 19
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(4-((6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)hexyl)amino)-4-oxobutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 20
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 21
  • [ 844442-38-2 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)-2,18-dioxo-7,10,13-trioxa-3,17-diazahenicosan-21-oyl)piperidin-4-yl)-1Hpyrazole-3-carboxamide [ No CAS ]
  • 22
  • [ 844442-38-2 ]
  • C21H24Cl2N6O5 [ No CAS ]
  • 23
  • [ 844442-38-2 ]
  • C23H28Cl2N6O5 [ No CAS ]
  • 24
  • [ 844442-38-2 ]
  • C23H28Cl2N6O7 [ No CAS ]
  • 25
  • [ 108-30-5 ]
  • [ 844442-38-2 ]
  • 4-(4-(4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxamido)piperidin-1-yl)-4-oxobutanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine; In dichloromethane; at 20.0℃; for 24.0h; Et3N (150muL, 1.1mmol, 3 eq) was added to a solution of <strong>[844442-38-2]4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide</strong>(1) (180mg, 0.37mmol, 1.0 eq) and succinic anhydride (44mg, 0.44mmol, 1.2 eq) in DCM. The solution was stirred at room temperature for 24h. After concentration, the residue was purified by flash column chromatography to afford the title compound (3) as a white solid (140mg, 80% yield). 1H NMR (400MHz, DMSO-d6) delta 10.17 (s, 1H), 8.38 (d, J=8.0Hz, 1H), 8.34 (s, 1H), 7.61-7.52 (m, 3H), 4.34 (d, J=12.8Hz, 1H), 3.97-3.89 (m, 2H), 3.04 (t, J=12.4Hz, 1H), 2.63-2.50 (m, 3H), 2.42-2.93 (m, 2H), 1.80-1.71 (m, 2H), 1.58-1.39 (m, 2H). HRMS (ESI+): calcd for C20H21Cl2N5O5Na [M+ Na]+ 504.0817, found 504.0812.
80% In dichloromethane; at 20.0℃; for 24.0h; In a 25 mL round bottom flask, 0.37 mmol of Intermediate 1 and 10 mL of dichloromethane were added,Then 0.44 mmol succinic anhydride was added at room temperature, and the reaction solution was stirred at room temperature for 24 h. The reaction solution was spin-dried and then passed through a silica gel column with dichloromethane: methanol 15: 1 to obtain intermediate 3 with a yield of 80%.
  • 26
  • [ 844442-38-2 ]
  • [ 57294-38-9 ]
  • tert-butyl (4-(4-(4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxamido)piperidin-1-yl)-4-oxobutyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 12.0h; DIPEA (46mg, 0.36mmol, 2.0 eq) and HATU (102mg, 0.27mmol, 1.5 eq) were added to a solution of 1 (70mg, 0.18mmol, 1.0 eq) and N-Boc-gamma-aminobutyric acid (47mg, 0.23mmol, 1.3 eq) in DMF (5mL). The reaction mixture was quenched with H2O and extracted with EtOAc. The organic layer was separated, washed with brine, dried, and evaporated. The residue was purified by flash column chromatography to afford 5a (60mg, 58% yield). 1H NMR (400MHz, CDCl3) delta 9.90 (s, 1H), 8.48 (d, J=2.8Hz, 1H), 7.35-7.27 (m, 3H), 4.91-4.80 (m, 1H), 4.63-4.53 (m, 1H), 4.25-4.07 (m, 1H), 3.94-3.81 (m, 1H), 3.23-3.08 (m, 2H), 2.80-2.66 (m, 1H), 2.39 (t, J=7.2Hz, 2H), 2.11-1.78 (m, 4H), 1.65-1.48 (m, 2H), 1.43 (s, 9H). HRMS (ESI+): calcd for C25H32Cl2N6O5Na [M+ Na]+ 589.1709, found 589.1703.
58% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 12.0h; Weigh 0.18mmol intermediate 1 and 0.27mmol HATU dissolved in 10mL DMF,Then add 0.36 mmol DIPEA and 0.23 mmol N-Boc-gamma-butyric acid,Reaction at room temperature for 12h.Quench the reaction with water and extract three times with ethyl acetate and then use petroleum ether: ethyl acetate 1: 1 through the silica gel column to obtain 5a, Yield 58%.
  • 27
  • [ 844442-38-2 ]
  • [ 6404-29-1 ]
  • tert-butyl (6-(4-(4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxamido)piperidin-1-yl)-6-oxohexyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 12.0h; General procedure: DIPEA (46mg, 0.36mmol, 2.0 eq) and HATU (102mg, 0.27mmol, 1.5 eq) were added to a solution of 1 (70mg, 0.18mmol, 1.0 eq) and N-Boc-gamma-aminobutyric acid (47mg, 0.23mmol, 1.3 eq) in DMF (5mL). The reaction mixture was quenched with H2O and extracted with EtOAc. The organic layer was separated, washed with brine, dried, and evaporated. The residue was purified by flash column chromatography to afford 5a (60mg, 58% yield).
38% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 12.0h; Weigh 0.18mmol intermediate 1 (or intermediate 2) and 0.27mmol HATU dissolved in 10mL DMF,Then, 0.36 mmol DIPEA and 0.23 mmol N-tert-butoxycarbonyl-6-aminocaproic acid were added and reacted at room temperature for 12 h.The reaction was quenched with water, and extracted three times with ethyl acetate and then passed through a silica gel column with petroleum ether: ethyl acetate 1: 1 to obtain intermediate 5b (or intermediate 6b),The yield is 62%.
  • 28
  • [ 844442-38-2 ]
  • C15H32N2O6 [ No CAS ]
  • tert-butyl (2-(2-(2-(4-(4-(2,6-dichlorobenzamido)-1H-pyrazole-3-carboxamido)piperidin-1-yl)-2-oxoethoxy)ethoxy)ethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 12.0h; General procedure: DIPEA (46mg, 0.36mmol, 2.0 eq) and HATU (102mg, 0.27mmol, 1.5 eq) were added to a solution of 1 (70mg, 0.18mmol, 1.0 eq) and N-Boc-gamma-aminobutyric acid (47mg, 0.23mmol, 1.3 eq) in DMF (5mL). The reaction mixture was quenched with H2O and extracted with EtOAc. The organic layer was separated, washed with brine, dried, and evaporated. The residue was purified by flash column chromatography to afford 5a (60mg, 58% yield).
  • 29
  • [ 844442-38-2 ]
  • [ 1416579-91-3 ]
  • 4-(2,6-dichlorobenzamido)-N-(1-((2',5-dioxo-4,5-dihydro-3H-spiro[furan-2,3'-indolin]-4-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 30
  • [ 844442-38-2 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With triethylamine In methanol for 48h; 7 Example 7: 4-(2,6-dichlorobenzamido)-N-(1-(((3R,3aS,9aR,10aS,10bS,E)-6,9a- dimethyl-2-oxo2,3,3a,4,5,8,9,9a,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan- 3yl)methyl)piperidin-4-yl)-1 H-pyrazole-3-carboxamide (compound 8) To a solution of parthenolide (16 mg, 0.064 mmol), triethylamine (20 pL) in methanol (2 mL) was added AT7519 (30 mg, 0.070 mmol) and the mixture was stirred for 48 h. Then the mixture was concentrated in vacuo and purified by prep HPLC. LCMS calculated for C31H37CI2N5O5 [M]+: 629.2; found 630.3.
  • 31
  • [ 844442-38-2 ]
  • [ 96-32-2 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; sodium iodide In acetonitrile at 80℃;
  • 32
  • [ 844442-38-2 ]
  • [ 3395-91-3 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; sodium iodide In acetonitrile at 80℃;
  • 33
  • [ 844442-38-2 ]
  • [ 4897-84-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; sodium iodide In acetonitrile at 80℃;
  • 34
  • [ 844442-38-2 ]
  • [ 5454-83-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; sodium iodide In acetonitrile at 80℃;
  • 35
  • [ 844442-38-2 ]
  • [ 14273-90-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; sodium iodide In acetonitrile at 80℃;
  • 36
  • [ 844442-38-2 ]
  • [ 54049-24-0 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; sodium iodide In acetonitrile at 80℃;
Same Skeleton Products
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