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Structure of 875629-26-8

Chemical Structure| 875629-26-8

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Product Details of [ 875629-26-8 ]

CAS No. :875629-26-8
Formula : C5H9NO2
M.W : 115.13
SMILES Code : O=C(C1CN(C)C1)O
MDL No. :MFCD11520621
InChI Key :OQTWISXQJKXTEM-UHFFFAOYSA-N
Pubchem ID :20653078

Safety of [ 875629-26-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 875629-26-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 32.62
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

40.54 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.12
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-2.71
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-0.75
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.38
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.59

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

1.22
Solubility 1910.0 mg/ml ; 16.6 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

2.41
Solubility 29600.0 mg/ml ; 257.0 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.48
Solubility 347.0 mg/ml ; 3.01 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-8.93 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.0

Application In Synthesis of [ 875629-26-8 ]

* 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 [ 875629-26-8 ]

[ 875629-26-8 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 875629-26-8 ]
  • [ 891270-42-1 ]
  • [ 891268-78-3 ]
  • 2
  • [ 875629-26-8 ]
  • C20H25N5O [ No CAS ]
  • [ 891266-24-3 ]
  • 3
  • [ 50-00-0 ]
  • [ 36476-78-5 ]
  • [ 875629-26-8 ]
YieldReaction ConditionsOperation in experiment
94% With hydrogen;palladium 10% on activated carbon; In methanol; water; under 3000.3 Torr; EXAMPLE IX1-methyl-azetidine-3-carboxylic acid200 mg azetidine-3-carboxylic acid are dissolved in 10 ml of methanol, combined with 165 mul of a 37percent solution of formaldehyde in water as well as 20 mg 10percent palladium on charcoal and hydrogenated at 4 bar until the hydrogen uptake has ended.Then the catalyst is eliminated by suction filtering, the solvent is eliminated in vacuo, the residue is taken up in methanol and toluene and the solvents are again eliminated in vacuo.Yield: 214 mg (94percent of theory)Mass spectrum (ESI+): m/z=116 [M+H]+
  • 4
  • [ 875629-26-8 ]
  • [ 1396776-39-8 ]
  • [ 1396776-23-0 ]
YieldReaction ConditionsOperation in experiment
[0848] Synthesis of Compound B-8: N-((4,6-dimethyl-2-oxo-l,2-dihydropyridin-3- yl)methyl)- 1 -isopropyl-6-( 1 -( 1 -methylazetidine-3 -carbonyl)piperidin-4-yl)- 1 H- pyrazolo[3,4-b]pyridine-4-carboxamideCompound B-8[0849] Step 1 : Synthesis of N-((4,6-dimethyl-2-oxo-l ,2-dihydropyridin-3-yl)methyl)-l- isopropyl-6-( 1 -( 1 -methylazetidine-3-carbonyl)- 1 ,2,3 ,6-tetrahydropyridin-4-yl)- 1 H- pyrazolo [3 ,4-b]pyridine-4-carboxamide[0850] N-((4,6-dimethyl-2-oxo-l ,2-dihydropyridin-3-yl)methyl)-l-isopropyl-6-(l , 2,3,6- tetrahydropyridin-4-yl)-lH-pyrazolo[3,4-b]pyridine-4-carboxamide (1 equiv.) was dissolved in DMSO, to which Et3N (3 equiv.) and 1 -methylazetidine-3 -carboxylic acid (2 equiv.) was added. The reaction mixture was stirred at room temperature for 15 min before PYBOP (1.5 equiv.) was added to it and stirring was continued overnight. After completion of the reaction, water was added to it. Extraction was carried out using DCM; the combined organic layers were washed with water, brine and dried over anhydrous Na2S04; filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to give the desired product.
  • 5
  • [ 875629-26-8 ]
  • 5-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
  • 5-phenyl-N-[trans-3-[[(1-methylazetidin-3-yl)formohydrazido]carbonyl]cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With N-ethyl-N,N-diisopropylamine; HATU; In fluorobenzene; at 20.0℃; for 3h; 1 -methylazetidine-3 -carboxylic acid (172.5 mg, 1.50 mmol, 1.50 eq.), HATU (456 mg, 1.20 mmol, 1.20 eq.) andDIEA (387 mg, 2.99 mmol, 3.00 eq.) were added to a solution of 5-phenyl-N-trans-3- (hydrazinecarbonyl)cyclobutyl]isoxazole-3-carboxamide (300 mg, 1.00 mmol, 1.00 eq., prepared according to example 20) in DMF (15 mL). The resulting solution was stirred for 3 hours at room temperature and then it was concentrated under vacuum. The crude product waspurified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, C18; mobile phase, MeCN/H20 = 5:95 increasing to MeCN/H20 = 95:5 within 15 mm; Detector, UV 254 nm. This resulted in 337 mg (85percent) of 5-phenyl-N-[trans-3-[[(1-methylazetidin-3- yl)formohydrazido]carbonyl]cyclobutyl] isoxazole-3 -carboxamide as a yellow solid. LC-MS (ES, mlz): [M+H] = 398.
  • 6
  • [ 875629-26-8 ]
  • 5-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
  • 5-phenyl-N-[trans-3-[5-(1-methylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
  • 7
  • [ 875629-26-8 ]
  • 3-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutyl]isoxazole-5-carboxamide [ No CAS ]
  • 3-phenyl-N-[trans-3-[[(1-methylazetidin-3-yl)formohydrazido]carbonyl]cyclobutyl]isoxazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20.0℃; for 2h; 1 -methylazetidine-3- carboxylic acid (172.5 mg, 1.50 mmol, 1.50 eq.), HATU (570 mg, 1.50 mmol, 1.50 eq.) and DIEA (387 mg, 2.99 mmol, 3.00 eq.) were added to a solution of 3-phenyl-N-[trans-3- (hydrazinecarbonyl)cyclobutyl]-isoxazole-5-carboxamide (300 mg, 1.00 mmol, 1.00 eq.) in DMF (10 mL) and then stirred for 2 hours at room temperature. The crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, C I 8; mobile phase, MeCN/H20 = 5:95 increasing to MeCN/H20 = 95:5 within 30 min; Detector, UV 254 nm to give 200 mg (50percent) of 3-phenyl-N-[/ra5-3-[[(l -methylazetidin-3- yl)formohydrazido]carbonyl]cyclobutyl]-isoxazole-5-carboxamide as an off-white solid; LC- MS (ES, m/z): [M+H]+ = 398.0.
  • 8
  • [ 875629-26-8 ]
  • 3-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutyl]isoxazole-5-carboxamide [ No CAS ]
  • 3-phenyl-N-[trans-3-[[(1-methylazetidin-3-yl)formohydrazido]carbonyl]cyclobutyl]-isoxazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% 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 2h; 1 -methylazetidine-3 - carboxylic acid (172.5 mg, 1.50 mmol, 1.50 eq.), HATU (570 mg, 1.50 mmol, 1.50 eq.) and DIEA (387 mg, 2.99 mmol, 3.00 eq.) were added to a solution of 3-phenyl-N-[trans-3- (hydrazinecarbonyl)cyclobutylj -isoxazole-5 -carboxamide (300 mg, 1.00 mmol, 1.00 eq.) inDMF (10 mL) and then stirred for 2 hours at room temperature. The crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, C18; mobile phase, MeCN/H20 = 5:95 increasing to MeCN/H20 = 95:5 within 30 mm; Detector, UV 254 nm to give 200 mg (50percent) of 3-phenyl-N-[trans-3-[[(1-methylazetidin-3- yl)formohydrazidoj carbonyll cyclobutyll -isoxazole-5-carboxamide as an off-white solid; LC20 MS (ES, m/z): [M+Hj = 398.0.
50% 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 2h; 1 -methylazetidine-3 -carboxylic acid (172.5 mg, 1.50 mmol, 1.50 eq.), HATU (570 mg, 1.50 mmol, 1.50 eq.) andDIEA (387 mg, 2.99 mmol, 3.00 eq.) were added to a solution of 3-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutylj -isoxazole-5 -carboxamide (300 mg, 1.00 mmol, 1.00 eq.) inDMF (10 mL) and then stirred for 2 hours at room temperature. The crude product waspurified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, C18;mobile phase, MeCN/H20 = 5:95 increasing to MeCN/H20 = 95:5 within 30 mm; Detector,UV 254 nm to give 200 mg (50percent) of 3-phenyl-N-[trans-3-[[(1-methylazetidin-3- yl)formohydrazidoj carbonyll cyclobutyll -isoxazole-5-carboxamide as an off-white solid; LCMS (ES, m/z): [M+Hj = 398.0.
  • 9
  • [ 875629-26-8 ]
  • 3-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutyl]isoxazole-5-carboxamide [ No CAS ]
  • 3-phenyl-N-[trans-3-[5-(1-methylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]cyclobutyl]isoxazole-5-carboxamide [ No CAS ]
  • 10
  • [ 875629-26-8 ]
  • 5-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
  • 5-phenyl-N-[trans-3-[[(1-methylazetidin-3-yl)formohydrazido]carbonyl]cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20.0℃; for 3h; l-methylazetidine-3- carboxylic acid (172.5 mg, 1.50 mmol, 1.50 eq.), HATU (456 mg, 1.20 mmol, 1.20 eq.) and DIEA (387 mg, 2.99 mmol, 3.00 eq.) were added to a solution of (hydrazinecarbonyl)cyclobutyl]isoxazole-3-carboxamide (300 mg, 1.00 mmol, 1.00 eq., prepared according to example 20) in DMF (15 mL). The resulting solution was stirred for 3 hours at room temperature and then it was concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, CI 8; mobile phase, MeCN/H20 = 5:95 increasing to MeCN/H20 = 95:5 within 15 min; Detector, UV 254 nm. This resulted in 337 mg (85percent) of 5-phenyl-N-[fras-3-[[(l-methylazetidin-3- yl)formohydrazido]carbonyl]cyclobutyl]isoxazole-3-carboxamide as a yellow solid. LC-MS (ES, m/z): [M+H]+ = 398.
  • 11
  • [ 875629-26-8 ]
  • 5-phenyl-N-[trans-3-(hydrazinecarbonyl)cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
  • 5-phenyl-N-[trans-3-[5-(1-methylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]cyclobutyl]isoxazole-3-carboxamide [ No CAS ]
  • 12
  • [ 875629-26-8 ]
  • 2-(4-aminophenyl)-3-(pyridin-3-yl)quinazolin-4(3H)-one dihydrochloride [ No CAS ]
  • N-(4-(3,4-dihydro-4-oxo-3-(pyridin-3-yl)quinazolin-2-yl)phenyl)-1-methylazetidine-3-carboxamide dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
10 mg A mixture of 2-(4-aminophenyl)-3-(pyridin-3-yl)quinazolin-4(3H)-one hydrochloride (50 mg, 0.13 mmol), l-methylazetidine-3-carboxylic acid (41 uL, 0.33 mmol), (1- [bis(dimethylamino)methylene]-lH-l,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate) (162 mg, 0.42mmol), diisopropylethyl amine ( 0.15 mL, 0.7 mmol) in dimethylformamide (1 mL) was stirred for 18 hours. The reaction was filtered and then purified by reverse phase -HPLC (3-35percent acetonitrile /water) to give the title compound (23 mg). The sample was converted to an HCl salt with 4N HCl in dioxane (10 mg). LC/MS: RT = 2.76 minutes, purity > 95percent, (M+l)+ = 412.02. NMR (300MHz, CD3OD) delta = 8.53 (d, /=8.2 Hz, 1H), 8.46 - 8.30 (m, 1H), 8.17 - 7.92 (m, 3H), 7.92 - 7.81 (m, 1H), 7.81 - 7.65 (m, 3H), 7.58 - 7.42 (m, 2H), 4.62 - 4.39 (m, 2H), 4.30 - 4.05 (m, 2H), 3.92 - 3.69 (m, 1H), 3.02 - 2.85 (m, 4H), 1.41 - 1.21 (m, 1H)
  • 13
  • [ 875629-26-8 ]
  • 2-(4-aminophenyl)thieno[3,2-d]pyrimidin-4(3H)-one hydrochloride [ No CAS ]
  • N-(4-(3,4-dihydro-4-oxothieno[3,2-d]pyrimidin-2-yl)phenyl)-1-methyl azetidine-3-carboxamide hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
12 mg A mixture of 2-(4-aminophenyl)thieno[3,2-d]pyrirnidin-4(3H)-one hydrochloride (43 mg, 0.15 mmol), diisopropylethyl amine (0.15 mL), (l-[bis(dimethylamino)methylene]-l.H-l ,2,3-triazoo[4,5- b]pyridinium 3-oxid hexafluorophosphate) (134 mg, 0.35 mmol), l-methylazetidine-3-carboxylic acid (36 mg, 0.31 mmol) and dimethylformamide (2 mL) was stirred for 18 hours. The reaction was filtered and then purified by reverse phase HPLC (3-35percent acetonitrile/water). To the product (26 mg) in ethyl acetate/methanol was added 4N HC1 in dioxane. The mixture was stirred 30 mins. The solid was collected by filtration, washed with ethyl acetate and dried to give the desired HC1 salt (12 mg). LC/MS: RT = 2.59 minutes, purity > 95percent, (M+l)+ = 341.02.)
  • 14
  • [ 875629-26-8 ]
  • 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-(((1S,2S,4S)-2-(methylamino)-4-(3-(trifluoromethyl)phenyl)cyclohexyl)amino)-N-(pyrimidin-4-yl)benzenesulfonamide [ No CAS ]
  • N-((1S,2S,5S)-2-((2-chloro-4-(N-(2,4-dimethoxybenzyl)-N-(pyrimidin-4-yl)sulfamoyl)-5-fluorophenyl)amino)-5-(3-(trifluoromethyl)phenyl)cyclohexyl)-N,1-dimethylazetidine-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
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 18h; [0377] To 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-(((1S,2S,4S)-2-(methylamino)-4-(3-(trifluoromethyl)-phenyl)cyclohexyl)amino)-N-(pyrimidin-4-yl)benzenesulfonamide (20 mg, 0.03 mmol) in DMF (0.3 mL) was added <strong>[875629-26-8]1-methylazetidine-3-carboxylic acid</strong> (5 mg, 0.04 mmol) followed by N,N-diisopropylethylamine (20 uL, 0.11 mmol) and HATU (13 mg, 0.03 mmol). The reaction mixture was stirred at room temperature for 18 hours then diluted with water and EtOAc. The organic layer was separated and washed with saturated aqueous NaHCO3, then aqueous saturated brine solution, dried over Na2SO4, filtered and concentrated to provide N-((1S,2S,5S)-2-((2-chloro-4-(N-(2,4-dimethoxybenzyl)-N-(pyrimidin-4-yl)sulfamoyl)-5-fluorophenyl)amino)-5-(3-(trifluoromethyl)phenyl)cyclohexyl)-N,1-dimethylazetidine-3-carboxamide which was used directly in the next step without further purification.
  • 15
  • [ 875629-26-8 ]
  • 2-((2-ethyl-7-methyl-5-(6-(1-methylazetidine-3-carbonyl)-2,6-diazaspiro[3.4]octan-2-yl)pyrazolo[1,5-a]pyridin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 47 2-((2-ethyl-7-methyl-5-(6-(1-methylazetidine-3-carbonyl)-2,6-diazaspiro[3.4]octan-2-yl)pyrazolo[1,5-a]pyridin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile (Compound 47) Compound 47 was prepared from 44b and <strong>[875629-26-8]1-methylazetidine-3-carboxylic acid</strong> in a manner analogous to Example 31. 1H NMR (400 MHz, CDCl3) delta 8.15 (dd, J=8.6, 5.5 Hz, 2H), 7.15 (t, J=8.6 Hz, 2H), 5.97 (s, 1H), 5.83 (d, J=2.6 Hz, 1H), 3.91-3.81 (m, 6H), 3.69 (s, 1H), 3.56 (t, J=5.9 Hz, 6H), 3.48-3.40 (m, 3H), 2.78-2.71 (m, 2H), 2.69 (d, J=2.1 Hz, 3H), 2.45 (d, J=4.1 Hz, 3H), 2.24 (t, J=6.9 Hz, 1H), 2.14 (t, J=7.0 Hz, 1H), 1.35-1.28 (m, 3H). LC-MS (ESI): m/z=599.3 [M+H]+
  • 16
  • [ 875629-26-8 ]
  • 2-((2-cyclopropyl-7-methyl-5-(6-(1-methylazetidine-3-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)pyrazolo[1,5-a]pyridin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 84 2-((2-cyclopropyl-7-methyl-5-(6-(1-methylazetidine-3-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)pyrazolo[1,5-a]pyridin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile (Compound 84) The title compound was prepared by the method substantially similar to that mentioned in Step 3 (Example 77), using <strong>[875629-26-8]1-methylazetidine-3-carboxylic acid</strong> afford Compound 84 as a yellow solid. 1H NMR (400 MHz, CDCl3) delta 8.21-8.11 (m, 2H), 7.16 (t, 2H), 5.92 (s, 1H), 5.81 (d, 1H), 4.27 (s, 2H), 4.18 (s, 2H), 4.10-3.98 (m, 4H), 3.89 (t, 2H), 3.61 (s, 3H), 3.44 (dt, 3H), 2.62 (s, 3H), 2.50 (s, 3H), 1.93-1.78 (m, 1H), 1.12-0.88 (m, 4H). LC-Ms m/z (ESI): 597.3[M+H+]
 

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