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Chemical Structure| 871014-19-6 Chemical Structure| 871014-19-6

Structure of 871014-19-6

Chemical Structure| 871014-19-6

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Product Details of [ 871014-19-6 ]

CAS No. :871014-19-6
Formula : C9H18N2O2
M.W : 186.25
SMILES Code : O=C(OC(C)(C)C)N[C@H]1C[C@H](N)C1
MDL No. :MFCD09040641
InChI Key :OPDOEOOBYOABCJ-UHFFFAOYSA-N
Pubchem ID :16228707

Safety of [ 871014-19-6 ]

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

Computational Chemistry of [ 871014-19-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.89
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 50.48
TPSA ?

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

64.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.23
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

0.61
Log Po/w (WLOGP)?

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

1.0
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.

0.56
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

0.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.89

Water Solubility

Log S (ESOL):?

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

-1.12
Solubility 14.3 mg/ml ; 0.0767 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.54
Solubility 5.43 mg/ml ; 0.0291 mol/l
Class?

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

Very 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

-1.12
Solubility 14.1 mg/ml ; 0.0755 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

Yes
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.

-7.0 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

1.0
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)

2.92

Application In Synthesis of [ 871014-19-6 ]

* 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 [ 871014-19-6 ]

[ 871014-19-6 ] Synthesis Path-Downstream   1~21

  • 1
  • [ 871014-18-5 ]
  • [ 871014-19-6 ]
  • 2
  • [ 871014-19-6 ]
  • [ 122-04-3 ]
  • [ 1239589-55-9 ]
  • 3
  • [ 871014-19-6 ]
  • [ 124-63-0 ]
  • [ 1443749-32-3 ]
  • 4
  • [ 871014-19-6 ]
  • [ 1452561-68-0 ]
  • 5
  • [ 871014-19-6 ]
  • [ 1452560-27-8 ]
  • 6
  • [ 615-20-3 ]
  • [ 871014-19-6 ]
  • [ 1452560-21-2 ]
YieldReaction ConditionsOperation in experiment
81% With dmap; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 110℃; for 2h; Tert-butyl(trans-3-aminocyclobutyl)carbamate (1.48 g, 7.95 mmol), 2-chlorobenzothiazole (1.6 ml, 12.93 mmol), 4-dimethylaminopyridine (0.051 g, 0.417 mmol), and diisopropylethylamine (3.0 ml, 17.25 mmol) were suspended in dry dimethylsulfoxide (5 mL) under nitrogen. The mixture was heated at 110 C. for 2 hours then cooled to room temperature. Then, the mixture was partitioned between 30% saturated ammonium chloride (300 mL) and ethyl acetate (300 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude product was triturated with 1:1 dichloromethane:hexane (50 mL total) at 40 C. The mixture was filtered through a sintered glass frit and the solids washed with additional 1:1 dichloromethane:hexane (10 mL) before drying under high vacuum to give tert-butyl(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl) carbamate (2.063 g, 6.46 mmol, 81% yield) as an off white solid
  • 7
  • [ 5470-18-8 ]
  • [ 871014-19-6 ]
  • [ 1452560-26-7 ]
YieldReaction ConditionsOperation in experiment
63.5% With potassium carbonate; In dimethyl sulfoxide; at 110℃; for 2h; Tert-butyl(trans-3-aminocyclobutyl)carbamate (1.38 g, 7.41 mmol), 2-chloro-3-nitropyridine (1.25 g, 7.88 mmol) and potassium carbonate (0.655 ml, 10.85 mmol) were combined in dry dimethylsulfoxide (20 mL) and heated at 110 C. After 2 hours the reaction was cooled and partitioned between ethyl acetate (300 mL) and water (300 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) gave the desired tert-butyl(trans-3-((3-nitropyridin-2-yl)amino)cyclobutyl)carbamate (1.45 g, 4.70 mmol, 63.5% yield).
  • 8
  • [ 871014-19-6 ]
  • [ 1201362-85-7 ]
  • [ 1452560-76-7 ]
YieldReaction ConditionsOperation in experiment
31.4% With tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl-(2?,4?,6?-triisopropyl-3,6-dimethoxy-[1,1?-biphenyl]-2-yl)phosphine; sodium t-butanolate; In 1,4-dioxane; at 100℃; for 3h;Inert atmosphere; A microwave vial containing a mixture of ethyl 2-(4-chloro-2-(methylthio)pyrimidin-5-yl)-2-methylpropanoate (2.08 g, 7.57 mmol), tert-butyl(trans-3-aminocyclobutyl)carbamate (1.551 g, 8.33 mmol), tris(dibenzylideneacetone) dipalladium (0) (0.520 g, 0.568 mmol), dicyclohexyl(2?,4?,6?-triisopropyl-3,6-dimethoxy-[1,1?-biphenyl]-2-yl)phosphine (0.731 g, 1.363 mmol) and sodium tert-butoxide (2.317 ml, 18.93 mmol) in dioxane (15 mL) was purged with argon and capped. The reaction mixture was heated at 100 C. for 3 hours, cooled, and partitioned between water (200 mL) and ethyl actate (200 mL). The organic was isolated and concentrated under reduced pressure. Purification using the ISCO eluting with 0-70% EtOAc/hexane to give the desired product tert-butyl(trans-3-(5,5-dimethyl-2-(methylthio)-6-oxo-5H-pyrrolo[2,3-d]pyrimidin-7(6H)-yl)cyclobutyl)carbamate (0.9 g, 2.378 mmol, 31.4% yield). m/z: 379.2 (M+1)
  • 9
  • [ 871014-19-6 ]
  • [ 1201362-85-7 ]
  • [ 1452561-89-5 ]
  • 10
  • [ 871014-19-6 ]
  • [ 1452561-64-6 ]
  • [ 1452560-95-0 ]
  • 11
  • [ 871014-19-6 ]
  • [ 1452561-77-1 ]
  • [ 1452561-45-3 ]
YieldReaction ConditionsOperation in experiment
47.4% With chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2?,4?,6?-tri-1-propyl-1,1?-biphenyl][2-(2-aminoethyl)phenyl]palladium(II); sodium t-butanolate; In 1,4-dioxane; at 50℃; for 0.5h;Inert atmosphere; Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate (intermediate 37, 0.343 g, 1.569 mmol), tert-butyl(trans-3-aminocyclobutyl)carbamate (0.292 g, 1.569 mmol), BrettPhos Precatalyst (0.125 g, 0.157 mmol), and sodium tert-butoxide (0.377 g, 3.92 mmol) were mixed in 1,4-dioxane (2 mL) under an argon atmosphere. The reaction mixture was heated to 50 C. and stirred for 30 min. The reaction mixture was diluted with water and extracted once with EtOAc. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel column chromatography eluting with EtOAc in hexanes to yield tert-butyl(trans-3-(6-fluoro-1-methyl-2-oxo-1 h-imidazo[4,5-b]pyridin-3(2h)-yl)cyclobutyl)carbamate (0.250 g, 0.743 mmol, 47.4% yield) as a white solid.
  • 12
  • [ 399-74-6 ]
  • [ 871014-19-6 ]
  • [ 1452562-01-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 120℃; for 2h; A mixture of tert-butyl(trans-3-aminocyclobutyl)carbamate (0.099 g, 0.533 mmol), 2-chloro-6-fluoro-1,3-benzothiazole (0.100 g, 0.533 mmol) and diisopropylethylamine (0.185 ml, 1.066 mmol) in DMSO (0.5 mL) contained in a microwave vial was capped and heated to 120 C. for 2 hrs. The mixture was diluted with water and extracted with EtOAc. EtOAc extract was concentrated to give crude tert-butyl(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)carbamate. To the crude tert-butyl(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)carbamate was added hydrogen chloride, 4N in 1,4-dioxane (10 ml, 40.0 mmol) and the resulting solution stirred at room temperature for 2 h and concentrated to afford crude trans-N1-(6-fluorobenzo[d]thiazol-2-yl)cyclobutane-1,3-diamine hydrochloride. The crude trans-N1-(6-fluorobenzo[d]thiazol-2-yl)cyclobutane-1,3-diamine hydrochloride was added to mixture of methyl (2-chloropyridin-3-yl)(methyl)carbamate, INTERMEDIATE 40, (0.107 g, 0.533 mmol), chloro(2-dicyclohexylphosphino-3,6-dimethoxy-2?-4?-6?-triisopropyl-1,1?-biphenyl)]2-(2-aminoethyl)Ph)Pd(II) (0.021 g, 0.027 mmol), and sodium tert-butoxide (0.261 ml, 2.132 mmol) in dioxane (10 mL). The mixture was stirred at 100 C. for 2 h and concentrated. The residue was diluted with water and extracted with EtOAc. EtOAc extract was concentrated and residue purified with ISCO on silica gel column eluting with 0-80% EtOAc/hexanes to give the title compound 3-(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (0.092 g, 0.249 mmol, 46.7% yield). m/z: 370.1 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) delta: ppm 8.07 (dd, J=5.18, 1.27 Hz, 1H), 7.49 (dd, J=8.90, 4.79 Hz, 1H), 7.32 (dd, J=8.12, 2.64 Hz, 1H), 7.17 (dd, J=7.73, 1.27 Hz, 1H), 6.97-7.07 (m, 2H), 5.90 (br. s., 1H), 5.33-5.50 (m, 1H), 4.48-4.74 (m, 1H), 3.48-3.67 (m, 2H), 3.43 (s, 3H), 2.34-2.63 (m, 2H).
  • 13
  • [ 871014-19-6 ]
  • [ 91524-96-8 ]
  • [ 1452561-01-1 ]
YieldReaction ConditionsOperation in experiment
66.6% With caesium carbonate; In dimethyl sulfoxide; at 70℃; Tert-butyl(trans-3-aminocyclobutyl)carbamate (0.150 g, 0.805 mmol) and intermediate 5 (0.120 g, 0.703 mmol) were dissolved in dry dimethylsulfoxide (3 mL) and cesium carbonate (0.123 ml, 1.535 mmol) was added. The reaction was heated at 70 C. After minutes the reaction was cooled and partitioned between water (100 mL) and ethyl acetate (200 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) gave the desired tert-butyl(trans-3-(thiazolo[5,4-b]pyridin-2-ylamino)cyclobutyl)carbamate (0.150 g, 0.468 mmol, 66.6% yield)
  • 14
  • [ 871014-19-6 ]
  • [ 1452561-74-8 ]
  • [ 1452560-42-7 ]
YieldReaction ConditionsOperation in experiment
86% With 2-(1H-9-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate; triethylamine; In dichloromethane; at 20℃; for 21h; 2-(2-Chloropyridin-3-yl)-2-methylpropanoic acid hydrochloride (intermediate 25, 992 mg, 4.20 mmol), tert-butyl(trans-3-aminocyclobutyl)carbamate (939 mg, 5.04 mmol), hatu (2077 mg, 5.46 mmol) and triethylamine (2.4 ml, 16.81 mmol) were dissolved in dichloromethane (8.4 mL). The reaction mixture was stirred at room temperature for 21 hours then diluted with water and extracted with dichloromethane. The organic was washed with saturated ammonium chloride and dried over magnesium sulfate. Evaporation under reduced pressure and purification using silica chromatography (0% to 100% ethyl acetate in hexane gradient) gave tert-butyl(trans-3-(2-(2-chloropyridin-3-yl)-2-methylpropanamido)cyclobutyl)carbamate (1327 mg, 3.61 mmol, 86% yield) as white solid.
  • 15
  • [ 871014-19-6 ]
  • [ 629616-88-2 ]
  • tert-butyl ((trans)-3-((2-((6-bromopyridin-2-yl)amino)-2-oxoethyl)amino)cyclobutyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 60℃; for 24h; To a solution of N-(6-bromopyridin-2-yl)-2-chloroacetamide (349a) (0.55 g, 2.204 mmol, prepared according to the procedure reported by Chenard, Bertand L. and Wu, Xinyuan; in PCT Int. Appl., 2016044792, 24 Mar 201 6) in THF (10 mL) was added DIPEA (0.578 mL, 3.31 mmol), tert-butyl (/ram)-3-aminocyclobutylcarbamate (0.452 g, 2.425 mmol) and stirred at 60 C for 24h. Mixture was poured into sat. NaHCCb solution (60 ml) and resultant suspension was extracted with EtOAc (2 x 80 ml). The combined organics were washed with brine, dried, filtered, concentrated and purified by flash column chromatography [silica gel 24 g, EtOAc in hexanes as eluents 0 to 100%] to afford tert-butyl ((iras)-3-((2-((6- bromopyridin-2-yl)amino)-2-oxoethyl)amino)cyclobutyl)carbamate (349b) (0.43 g, 49 % yield) as off-white solid; NMR (300 MHz, VMSO-de) delta 10.45 (s, 1H), 8.10 (dd, J = 8.1, 0.7 Hz, 1H), 7.75 (t, J = 8.0 Hz, 1H), 7.35 (dd, J = 7.7, 0.7 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 4.09 - 3.93 (m, 1H), 3.27 - 3.14 (m, 3H), 2.03 - 1.89 (m, 4H), 1.36 (s, 9H); MS (ES+): 421.3, 423.3 (M+Na), MS (ES-): 397.3, 399.3 (M-l).
  • 16
  • [ 871014-19-6 ]
  • [ 23688-89-3 ]
  • tert-butyl ((trans)-3-(6-chloropyrazine-2-carboxamido)cyclobutyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% Step 1: tert-Butyl ((trans)-3-(6-chloropyrazine-2-carboxamido)cyclobutyl)carbamate A stirred solution of 6-chloropyrazine-2-carboxylic acid (0.25 g, 1.58 mmol) in DMF (3 mL) was added with DIPEA (0.42 mL, 2.37 mmol) and HATU (0.72 g, 1.9 mmol). The reaction mixture was stirred at room temperature for 20 minutes. A solution of <strong>[871014-19-6]tert-butyl (trans-3-aminocyclobutyl)carbamate</strong> (0.32 g, 1.74 mmol) in DMF (3 mL) was added and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate and was washed sequentially with saturated aqueous sodium hydrogen carbonate (*2) and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated at reduced pressure to afford the title compound (0.530 g, 93%). 1H NMR (400 MHz, DMSO-d6); delta 9.18 (d, J=7.5 Hz, 1H), 9.11 (s, 1H), 9.01 (s, 1H), 7.30 (d, J=7.0 Hz, 1H), 4.54-4.49 (m, 1H), 4.08-4.01 (m, 1H), 2.70 (s, 1H), 2.48-2.39 (m, 2H), 2.27-2.19 (m, 2H), 1.40 (s, 9H).
  • 17
  • [ 871014-19-6 ]
  • [ 23688-89-3 ]
  • tert-butyl (trans-3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazine-2-carboxamido)cyclobutyl)carbamate [ No CAS ]
  • 18
  • [ 871014-19-6 ]
  • 1-(3,4-dimethyl-2-p-tolyl-2H-pyrazolo[4,3-d]pyridazin-7-yl) piperidine-4-carboxylic acid [ No CAS ]
  • tert-butyl (1r,3r)-3-(1-(3,4-dimethyl-2-p-tolyl-2H-pyrazolo[3,4-d]pyridazin-7-yl)piperidine-4-carboxamido)cyclobutylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 16h; To a solution of 1.6 (200 mg, 0.548 mmol), tert-butyl (1r,3r)-3- aminocyclobutylcarbamate (122 mg, 0.658 mmol), HOBt (248 mg, 1.096 mmol) and TEA (166 mg, 1.644 mmol) in DCM (10 mL) was added EDCI (210 mg, 1.096 mmol) portion wise under ice-water bath. The reaction mixture was then stirred at RT for 16 h. Upon completion, the reaction mass was diluted with DCM (50 mL) and washed with water (30 mL) and brine (30 mL). The organic layer was dried over Na2S04 and concentrated in vacuo. The crude product was purified on prep-TLC using 9% MeOH/DCM to afford 12a.1 (190 mg, 65.0% yield) as white solid. LCMS (ESI+) m/z = 534 (M+H).
  • 19
  • [ 871014-19-6 ]
  • [ 1276113-64-4 ]
  • benzyl N-[(3S)-5-oxo-1-[(1r,3r)-3-[[(tertbutoxy)carbonyl]amino]cyclobutyl]pyrrolidin-3-yl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
800 mg A solution of <strong>[871014-19-6]tert-butyl N-[(trans)-3-aminocyclobutyl]carbamate</strong> (545 mg, 2.78 mmol) and methyl (3S)-3-[[(benzyloxy)carbonyl]amino]-4-oxobutanoate (820 mg, 2.78 mmol) in DCM (30 mL) was stirred for 1 h at 25 C. Sodium triacetoxyborohydride (807 mg, 3.62 mmol) was added in two portions, and the resulting mixture was stirred for additional 14 h at 25 C. The reaction was quenched by the addition of water/ice (30 mL). The resulting mixture was extracted with DCM (2 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was treated with DMF (5 mL). The solids were collected by filtration, washed with MeOH (3 x 10 mL) and dried in an oven to afford benzyl N-[(3S)-5-oxo-l-[(trans)-3-[[(tert- butoxy)carbonyl]amino]cyclobutyl]pyrrolidin-3-yl]carbamate as a white solid (800 mg). LCMS (ES, m/z) 404 [M+H]+.
  • 20
  • [ 957346-62-2 ]
  • [ 871014-19-6 ]
  • tert-butyl ((trans)-3-(5-bromothiazole-2-carboxamido)cyclobutyl)carbamate [ 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℃; for 1h;Inert atmosphere; Into a 100 mL round-bottom flask was placed 5-bromothiazole-2-carboxylic acid (300 mg, 1.41 mmol), N,N-dimethylformamide (5 mL), tert-butyl N-[(trans)-3- aminocyclobutyl]carbamate (270 mg, 1.42 mmol), N,N-diisopropylethylamine (560 mg, 4.33 mmol) and HATU (661 mg, 1.74 mmol). The resulting solution was stirred for 1 h at room temperature. The reaction mixture was poured into water (5 mL) and then extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by prep-TLC (eluting with 1 : 1 ethyl acetate/petroleum ether) to afford tert-butyl ((trans)-3-(5-bromothiazole-2- carboxamido)cyclobutyl)carbamate as a yellow solid. LC-MS (ESI) m/z 320.0, 322.0 [M+H-tBu]+
  • 21
  • [ 871014-19-6 ]
  • tert-butyl ((trans)-3-(5-phenylthiazole-2-carboxamido)cyclobutyl)carbamate [ No CAS ]
 

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