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Chemical Structure| 2038-03-1 Chemical Structure| 2038-03-1

Structure of 2038-03-1

Chemical Structure| 2038-03-1

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Product Citations

Product Citations

Li, Bowen ; Manan, Rajith Singh ; Liang, Shun-Qing ; Gordon, Akiva ; Jiang, Allen ; Varley, Andrew , et al.

Abstract: The expanding applications of nonviral genomic medicines in the lung remain restricted by delivery challenges. Here, leveraging a high-throughput platform, we synthesize and screen a combinatorial library of biodegradable ionizable lipids to build inhalable delivery vehicles for mRNA and CRISPR-Cas9 gene editors. Lead lipid nanoparticles are amenable for repeated intratracheal dosing and could achieve efficient gene editing in lung epithelium, providing avenues for gene therapy of congenital lung diseases.

Alternative Products

Product Details of [ 2038-03-1 ]

CAS No. :2038-03-1
Formula : C6H14N2O
M.W : 130.19
SMILES Code : NCCN1CCOCC1
MDL No. :MFCD00006182
InChI Key :RWIVICVCHVMHMU-UHFFFAOYSA-N
Pubchem ID :408285

Safety of [ 2038-03-1 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314-H317
Precautionary Statements:P260-P264-P270-P272-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P333+P313-P362+P364-P405-P501
Class:8
UN#:3259
Packing Group:

Computational Chemistry of [ 2038-03-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 39.45
TPSA ?

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

38.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.64
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

-1.05
Log Po/w (WLOGP)?

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

-1.1
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.

-0.67
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

0.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.18

Water Solubility

Log S (ESOL):?

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

0.15
Solubility 182.0 mg/ml ; 1.4 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.

0.73
Solubility 699.0 mg/ml ; 5.37 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 43.2 mg/ml ; 0.332 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

Low
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.

-7.84 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)

1.55

Application In Synthesis of [ 2038-03-1 ]

* 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 [ 2038-03-1 ]

[ 2038-03-1 ] Synthesis Path-Downstream   1~20

  • 1
  • [ 2038-03-1 ]
  • [ 7477-77-2 ]
  • 4-Hydroxy-N-(2-morpholin-4-yl-ethyl)-3-(2-morpholin-4-yl-ethylamino)-4,4-diphenyl-butyramide [ No CAS ]
  • 2
  • [ 2038-03-1 ]
  • [ 1022-13-5 ]
  • [ 80170-85-0 ]
  • [ 80171-07-9 ]
  • 3
  • [ 2038-03-1 ]
  • [ 40106-98-7 ]
  • (2-Morpholin-4-yl-ethyl)-(5-nitro-quinolin-4-yl)-amine [ No CAS ]
  • 4
  • [ 2038-03-1 ]
  • [ 263351-43-5 ]
  • [ 1028338-70-6 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; potassium carbonate; L-proline; In dimethyl sulfoxide; at 80℃; for 1h; Example 151: Synthesis of 4-Chloro-6-[3-(2-morpholin-4-yl-ethylamino)- benzylamino]-2H-phthalazin-l -one hydroformate; [3-(2-Morpholin-4-yl-ethylamino)-benzyl]-carbamic acid isopropyl ester; A mixture of <strong>[263351-43-5](3-iodo-benzyl)-carbamic acid tert-butyl ester</strong> (272mg, 0.816mmol),4-(2-aminoethyl)morpholine (O.lbetamL, 1.225 mmol), K2CO3 (232mg, 1.679 mmol), CuI <n="118"/>(19mg, 0.10 mmol), L-proline (19mg, 0.163mmol) and DMSO (5 mL) was heated at 85C for Ih. The reaction was cooled, poured onto water and the aqueous layer extracted with EtOAc (x3). The organic layers were combined and washed with water, brine and dried (Na2SO4). Chromatography (MeOH/EtOAc) afforded [3-(2-morpholin-4-yl- ethylamino)-benzyl]-carbamic acid isopropyl ester (200mg) as an orange viscous oil. m/z (M+l) 336.16.
  • 5
  • [ 4795-29-3 ]
  • [ 7154-73-6 ]
  • [ 2038-03-1 ]
  • [ 4572-03-6 ]
  • [ 27757-85-3 ]
  • [ 109-12-6 ]
  • [ 3731-53-1 ]
  • [ 107-10-8 ]
  • [ 7663-77-6 ]
  • [ 6628-04-2 ]
  • [ 2620-50-0 ]
  • polystyrene carboxaldehyde resin [ No CAS ]
  • [ 5071-96-5 ]
  • [ 617-89-0 ]
  • [ 28466-26-4 ]
  • [ 42185-03-5 ]
  • [ 453-71-4 ]
  • [ 19293-58-4 ]
  • [ 75-04-7 ]
  • [ 62-53-3 ]
  • [ 1003-03-8 ]
  • [ 51387-90-7 ]
  • [ 74-89-5 ]
  • [ 100-46-9 ]
  • [ 4152-90-3 ]
  • [ 68-41-7 ]
  • C9H8FN2O3Pol [ No CAS ]
  • C10H10FN2O3Pol [ No CAS ]
  • C11H12FN2O3Pol [ No CAS ]
  • C14H10FN2O3Pol [ No CAS ]
  • C11H8FN4O3Pol [ No CAS ]
  • C12H8FN4O3Pol [ No CAS ]
  • C13H10FN2O4Pol [ No CAS ]
  • C15H12FN2O3Pol [ No CAS ]
  • C14H11FN3O3Pol [ No CAS ]
  • C13H14FN2O3Pol [ No CAS ]
  • C13H10FN2O3PolS [ No CAS ]
  • C13H16FN2O4Pol [ No CAS ]
  • C13H14FN2O4Pol [ No CAS ]
  • C16H14FN2O4Pol [ No CAS ]
  • C11H9FN3O5Pol [ No CAS ]
  • C15H11ClFN2O3Pol [ No CAS ]
  • C17H17FN3O3Pol [ No CAS ]
  • C14H17FN3O3Pol [ No CAS ]
  • C14H17FN3O4Pol [ No CAS ]
  • C15H19FN3O3Pol [ No CAS ]
  • C16H12FN2O5Pol [ No CAS ]
  • C18H13FN3O3Pol [ No CAS ]
  • C15H17FN3O4Pol [ No CAS ]
  • C16H22FN4O3Pol [ No CAS ]
YieldReaction ConditionsOperation in experiment
A library of compounds in which R4 was various groups having the formula [CONHR »] was prepared by the process described above using 4-fluoro-3-nitrobenzoic acid, as follows: [72] Aldehyde resin was mixed with a primary amine (R17-NH2) in [DICHLOROETHANE] (DCE), triethylorthoformate (TEOF), and DMF (containing [1%] acetic acid) in a 1: 1: 1 ratio. After shaken overnight, sodium triacetoxyborohydride (20 eq. ) dissolved in DMF was added (Abdel-Magid, A. F. , et al., Tetrahedron Lett, 3 1: 5595-5598 (1990) ). After the mixture was shaken at room temperature overnight, the resin was filtered and washed with DMF (3 x 5 mL), [MEOH] [(3 X 5] mL), DMF [(3 X 5] mL), [MEOH] [(3 X 5] mL), and [CH2CL2] [(3 X 5] mL). The resin was washed twice with 5 mL DMF containing [1%] Hunig's base. To the filtered resin was added a mixture of 4-fluoro-3-nitrobenzoic acid (FNBA, 10 eq. ) and diisopropylcarbodiimide (DIC, 5 eq. ) in 2: 1 DMF : DCM. After shaking at room temperature overnight, the resin was filtered and washed with DMF (3 x 5 mL) and [CH2C12] (3 x 5 mL). [73] The resin was shaken with a primary amine [(R2-NH2)] in DMF for 8 hrs, filtered, and washed with DMF (6 x 5 mL), [MEOH] [(3 X 5] mL), and CH2C12 (3 x 5 mL). The aryl nitro group was reduced by the addition of tin (II) chloride dihydrate (20 eq. , >2 M) and N-methyl morpholine (NMM, 20 eq. ) in N-methyl pyrrolidinone (NMP). After shaken at room temperature overnight, the resin was filtered and washed with NMP (3 x 5 mL), [MEOH] (3 x 5 mL), and [CH2CI2 (3 X 5] mL). The resulting resin was shaken at room temperature with cyanogen bromide (5 eq. ) overnight, filtered, and washed with CH2Cl2 (3 x 5 mL), [MEOH] (3 x 5 mL), and CH2CI2 (3 x 5 mL). To produce a free amine, the resin was shaken for 30 min. in CHCl2 with the addition of sodium methoxide in methanol, filtered, and washed with CH2Cl2 [(4 X 5] mL). [[74]] In the final diversification step, the resin was heated at 500 C in DMF with a mono- substituted epoxide [[RLCH (-CH2O-)].] After shaking for 2 to 4 days the resin was filtered and washed with DMF (5 x 5 mL), [MEOH] [(3 X 5] mL), and CH2Cl2 (3 x 5 mL). T he resin-bound benzimidazole was cleaved from the solid-support by treatment with TFA: [CH2C12] (2: 3) for 1 hour at room temperature.
  • 6
  • [ 2038-03-1 ]
  • [ 2882-15-7 ]
  • C18H25N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 2h; General procedure: Method 2: to the solution of Indomethacin (100 mg, 0.28 mmol), the corresponding amine (0.28 mmol), and PyBOP (145.7 mg, 0.28 mmol) in anhydrous dimethylformamide was added triethylamine (56.5 mg, 0.56 mmol) and the mixture was stirred at room temperature for 2 h. Then saturated sodium chloride solution was added. The reaction mixture was extracted using ethyl acetate (3 x 50 ml). The combined organic layers werewashed successively with water, 5% aqueous sodium bicarbonate, and then concentrated under vacuum. The obtained crude product was purified by recrystallization or silica gel column chromatography.
  • 7
  • [ 2038-03-1 ]
  • [ 161622-05-5 ]
  • [ 1415400-80-4 ]
YieldReaction ConditionsOperation in experiment
70% With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃; General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.
  • 8
  • [ 2038-03-1 ]
  • [ 51419-59-1 ]
  • [ 950243-40-0 ]
  • 9
  • [ 2038-03-1 ]
  • [ 42237-85-4 ]
  • [ 1525616-82-3 ]
YieldReaction ConditionsOperation in experiment
92% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 0 - 20℃; for 19h; Intermediate D1 : 3-Amino-5-ethynyl-A -(2-morpholinoethyl)benzamide. To a suspension of T3P (2.76 mL, 4.63 mmol), <strong>[42237-85-4]3-amino-5-bromobenzoic acid</strong> (1.00 g, 4.63 mmol) and Et3N (1.9 mL, 14 mmol) in DCM (20 mL) at 0C was added 2-morpholino ethanamine (0.91 mL, 6.9 mmol) and the mixture allowed to warm to RT for 18 hr. Additional aliquots of T3P (2.76 mL, 4.63 mmol) and 2-morpholinoethanamine (0.91 mL, 6.9 mmol) were added and after 1 hr the resulting mixture was partitioned with sat. aq NaHC03 (20 mL). The aq layer was separated and was extracted with DCM (20 mL) and the combined organics layers were washed with brine and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, 40 g, MeOH in DCM, 2-5%, gradient elution) to afford 3-amino-5-bromo-/V-(2-morpholinoethyl)benzamide as a yellow crystalline solid (1.4 g, 92%); Rl 0.16 min (Method 2 acidic); m/z 328/330 (M+H)+ (ES+). To a degassed suspension of the benzamide obtained above (500 mg, 1.52 mmol), copper(l) iodide (29.0 mg, 0.152 mmol), and ethynyltriisopropylsilane (0.51 mL, 2.3 mmol) in a mixture of Et3N (3.0 mL) and DMF (3.0 mL), was added Pd(PPh3)4 (176 mg, 0.152 mmol) and the mixture heated to 80C for 1 hr, and then cooled to RT. The solids were removed by filtration through celite and the volatiles evaporated in vacuo to provide a crude product which was purified by flash column chromatography (Si02,12 g, MeOH in DCM, 5-10%, gradient elution) to afford 3-amino-/V-(2-morpholinoethyl)-5-((triisopropylsilyl)ethynyl)benzamide as a pale yellow gum (600 mg, 92%); Rl 1.84 min (Method 2 acidic); m/z 430 (M+H)+ (ES+) To a solution of the alkynylsilane obtained above (500 mg, 1.164 mmol) in THF (5.0 mL) was added TBAF (116 mL, 1.16 mmol) and the mixture maintained at RT for 1h. An additional aliquot of TBAF (114 mu, 1.16 mmol) was added and after 30 min the reaction mixture was partitioned between water (10 mL) and ethyl acetate (10 mL). The organic layer was separated and was washed with brine and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (Si02,12 g, MeOH in DCM, 2-5%, gradient elution) to afford the title compound Intermediate D1 , as a colourless gum (260 mg, 82%); R' 1.17 min (Method 2 basic); LCMS m/z 274 (M+H)+ (ES+).
1.4 g With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; 2-Morpholinoethanamine (0.911 mL, 6.94 mmol) was added to an ice cold suspension ofT3P (1-propanephosphonic acid cyclic anhydride) (2.76 mL, 4.63 mmol), <strong>[42237-85-4]3-amino-5-bromobenzoic acid</strong> (ig, 4.63 mmol) and TEA (1.936 mL, 13.89 mmol) in DCM (20m1)Allowed to warm to room temperature and stirred overnight. More T3P (2.76 mL, 4.63 mmcl) and 2-morpholinoethanamine (0.911 mL, 6.94 mmol) were added and stirred for a further lh. Partitioned with sat. NaHCO3 soin. (20m1), the aqueous layer separated and partitioned with fresh DCM (20m1). The organics separated, bulked and partitioned with 20%wlw NaCI soln. The organic layer was separated, dried (MgSO4) filtered and solventevaporated. The crude product was purified by chromatography on the Companion (40 gcolumn, 2% MeOH:DCM to 5%) to afford the sub-title compound (1.4g) as a yellowcrystalline solid.1H NMR (400 MHz, DMSO-d6) O 8.28 (t, 1H), 7.06 (t, 1H), 6.98 (dd, 1H), 6.85 (t, 1H),5.58 (s, 2H), 3.57 (t, 4H), 3.33 (m, 2H), 2.41 (m, 6H).LCMS m/z 328/330 (Mi-H) (ES)
13 g With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 20 - 35℃; for 1h; T3P (50Wt% in EtOAc, 56.2 mL, 94 mmol), was added carefully to a solution of 3-amino- 5-bromobenzoic acid (13.6 g, 63.0 mmol), 2-morpholinoethanamine (16.52 mL, 126 mmol) and TEA (26.3 mL, 189 mmol) in DCM (200 mL). Ice bath used sporadically to prevent temperature rising above 35C. Stirred at rt for 1 h then partitioned with sat. aq. NaHC03 soln. (250 mL). Aqueous separated and partitioned with fresh DCM (250 mL), organics separated, bulked and partitioned with 20%w/w NaCI soln. (250 mL). Organic layer was separated, dried (MgS04), filtered and solvent evaporated. The crude product was dissolved in DCM (100 mL) and the sub-title product (13 g) crystallised out on standing as a light tan crystalline solid. 1 H NMR (400 MHz, DMSO-d6) delta 8.29 (t, 1 H), 7.06 (t, 1 H), 6.98 (t, 1 H), 6.85 (t, 1 H), 5.59 (s, 2H), 3.57 (t, 4H), 3.41 - 3.26 (m, 2H), 2.48 - 2.33 (m, 6H) LCMS m/z 328/330(M+H)+
13 g With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 20 - 35℃; for 3h; T3P (50% w/w in EtOAc, 56.2 mL, 94 mmol), was added carefully to a solution of <strong>[42237-85-4]3-amino-5-bromobenzoic acid</strong> (13.6 g, 63.0 mmol), 2-morpholinoethanamine (16.52 mL, 126 mmol) and Et3N (26.3 mL, 189 mmol) in DCM (200 mL). An ice bath was used sporadically to prevent temperature rising above 35 C. Reaction stirred at room temperature for 1 h. Partitioned with sat. aq. NaHCO3 solution (250 mL). Aqueous separated and partitioned with fresh DCM (250 mL). Organics separated, bulked and partitioned with 20% w/w NaCl solution (250 mL). The organic layer was separated, dried (MgSO4), filtered and solvent evaporated. The crude product was dissolved in DCM (100 mL) and the sub-title compound (13 g) crystallised out on standing as a light tan crystalline solid. 1H NMR (400 MHz, DMSO-d6) delta 8.29 (t, 1H), 7.06 (t, 1H), 6.98 (t, 1H), 6.85 (t, 1H), 5.59 (s, 2H), 3.57 (t, 4H), 3.41-3.26 (m, 2H), 2.48-2.33 (m, 6H). LCMS m/z 328/330(M+H)+ (ES+)
13 g With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 20 - 35℃; for 1h; T3P (50% wlw in EtOAc, 56.2 mL, 94 mmol), was added carefully to a solution of <strong>[42237-85-4]3-amino-5-bromobenzoic acid</strong> (13.6 g, 63.0 mmol), 2-morpholinoethanamine (16.52 mL, 126 mmol) andEt3N (26.3 mL, 189 mmol) in DCM (200 mL). An ice bath was used sporadically to preventtemperature rising above 35C. Reaction stirred at room temperature for lh. Partitionedwith sat. aq. NaHCO3 solution (250 mL). Aqueous separated and partitioned with fresh DCM (250 mL). Organics separated, bulked and partitioned with 20%wlw NaCI solution (250 mL). The organic layer was separated, dried (MgSO4), filtered and solvent evaporated. The crude product was dissolved in DCM (100 mL) and the sub-title compound (13 g) crystallised outon standing as a light tan crystalline solid.1H NMR (400 MHz, DMSO-d6) O 8.29 (t, 1H), 7.06 (t, 1H), 6.98 (t, 1H), 6.85 (t, 1H), 5.59 (5, 2H), 3.57 (t, 4H), 3.41 - 3.26 (m, 2H), 2.48 - 2.33 (m, 6H).LCMS mlz 328/330(M+H) (ES)
13 g With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 20 - 35℃; for 1h; (i) 3-Ami no-5-bromo-N-(2-morphol inoethyl) benzam ideT3P (50% w/w in EtOAc, 56.2 ml, 94 mmcl), was added carefully to a solution of 3-amino-5-bromobenzcic acid (13.6 g, 63.0 mmcl), 2-mcrpholincethanamine (16.52 mL, 126 mmcl) andEt3N (26.3 mL, 189 mmol) in DCM (200 mL). An ice bath was used sporadically to prevent temperature rising above 35C. Reaction stirred at room temperature for I h. Partitioned with sat. eq. NaHCO3 solution (250 mL). Aqueous separated and partitioned with fresh DCM (250 mL). Organics separated, bulked and partitioned with 20%wlw NaCI solution (250 mL).The organic layer was separated, dried (MgSO4), filtered and solvent evaporated. The crude product was dissolved in DCM (100 mL) and the sub-title compound (13 g) crystallised cut on standing as a light tan crystalline solid.1H NMR (400 MHz, DMSO-d6) O 8.29 (t, IH), 7.06 (t, IH), 6.98 (t, IH), 6.85 (t, IH), 5.59 (s, 2H), 3.57 (t, 4H), 3.41 - 3.26 (m, 2H), 2.48 - 2.33 (m, 6H).LCMS m/z 328/330(M+H) (ES)
1.4 g With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; 2-Morpholinoethanamine (0.911 mL, 6.94 mmol) was added to an ice cold suspension of T3P (2.76 mL, 4.63 mmol), <strong>[42237-85-4]3-amino-5-bromobenzoic acid</strong> (1 g, 4.63 mmol) and TEA (1.936 mL, 13.89 mmol) in DCM (20 mL). Allowed to warm to room temperature and stirred overnight. More T3P (2.76 mL, 4.63 mmol) and 2-morpholinoethanamine (0.911 mL, 6.94 mmol) were added and stirred for a further 1 h. Partitioned with saturated NaHCO3 solution (20 mL), the aqueous layer separated and partitioned with fresh DCM (20 mL). The organics separated, bulked and partitioned with 20% w/w NaCl solution. Organic layer separated, dried (MgSO4) filtered and solvent evaporated. The crude product was purified by chromatography on the Companion (40 g column, 2% MeOH:DCM to 5%) to afford the sub-title compound (1.4 g) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO) delta 8.28 (t, 1H), 7.06 (t, 1H), 6.98 (dd, 1H), 6.85 (t, 1H), 5.58 (s, 2H), 3.57 (t, 4H), 3.33 (m, 2H), 2.41 (m, 6H). LCMS m/z 328/330 (M+H)+ (ES+)
1.4 g With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃; for 1h; (i) 3-Amino-5-bromo-N-(2-morpholinoethyl)benzamide 2-Morpholinoethanamine (0.911 mL, 6.94 mmol) was added to an ice cold suspension of T3P (2.76 mL, 4.63 mmol), <strong>[42237-85-4]3-amino-5-bromobenzoic acid</strong> (1 g, 4.63 mmol) and TEA (1.936 mL, 13.89 mmol) in DCM (20 mL). Allowed to warm to room temperature and stirred overnight. More T3P (2.76 mL, 4.63 mmol) and 2-morpholinoethanamine (0.911 mL, 6.94 mmol) were added and stirred for a further 1 h. Partitioned with saturated NaHCO3 solution (20 mL), the aqueous layer separated and partitioned with fresh DCM (20 mL). The organics separated, bulked and partitioned with 20% w/w NaCl solution. Organic layer separated, dried (MgSO4) filtered and solvent evaporated. The crude product was purified by chromatography on the Companion (40 g column, 2% MeOH:DCM to 5%) to afford the sub-title compound (1.4 g) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO) delta 8.28 (t, 1H), 7.06 (t, 1H), 6.98 (dd, 1H), 6.85 (t, 1H), 5.58 (s, 2H), 3.57 (t, 4H), 3.33 (m, 2H), 2.41 (m, 6H). LCMS m/z 328/330 (M+H)+ (ES+)

  • 10
  • [ 2038-03-1 ]
  • copper(II) nitrate trihydrate [ No CAS ]
  • [ 32596-43-3 ]
  • C20H28ClN4O3(1-)*2NO3(1-)*H2O*2Cu(2+)*HO(1-) [ No CAS ]
  • 11
  • [ 2038-03-1 ]
  • [ 3328-69-6 ]
  • [ 1163155-76-7 ]
YieldReaction ConditionsOperation in experiment
In methanol; at 2℃;Reflux; To a 20mL methanolic solution of DFP (0.065 g, 0.4 mmol), 4-(2-aminoethyl)morpholine (0.104 g, 0.8 mmol) was added. The resulting mixture was stirred for 15 min and then it was refluxed for 2 h. This ?solution of HL1? was used for subsequent reactions without isolation and further purification or characterization.
  • 12
  • [ 2038-03-1 ]
  • [ 6492-86-0 ]
  • [ 159641-18-6 ]
YieldReaction ConditionsOperation in experiment
83% In ethanol; for 24h;Reflux; To a solution of <strong>[6492-86-0]4-amino-1,8-naphthalic anhydride</strong>(1.07 g, 5 mmol) in ethanol (100 mL) added 4-(2-aminoethyl)-morpholine(1.31g, 1.0 mmol). The reaction was refluxed for 24 h and thencooled to room temperature. The solvent was removed and the crudeproduct was purified by gel column chromatography with CH2Cl2/CH3OH as eluent (SiO2, v/v, 50:1 to 10:1) to afford the correspondingproduct as pale yellow solid (1.34 g, yield: 83%). 1H NMR (400 MHz,CDCl3) delta 8.60 (d, J=7.2, 1H), 8.41 (d, J=8.2 Hz, 1H), 8.10 (dd,J=8.4, 1.0 Hz, 1H), 7.67 (dd, J=8.4, 7.2 Hz, 1H), 6.89 (d, J=8.2 Hz,1H), 4.33 (dd, J=7.6, 7.0 Hz, 2H), 3.78-3.55 (m, 4H), 2.70 (dd,J=7.6, 6.8 Hz, 2H), 2.67-2.52 (m, 4H). 13C NMR (101 MHz, DMSO-d6)delta 163.72, 162.82, 152.68, 133.85, 130.85, 129.66, 129.20, 123.85,121.70, 119.32, 108.08, 107.49, 66.20, 55.79, 53.41, 36.34. EdSI-MSm/z [(M + H)+]: 326.1.
  • 13
  • [ 2038-03-1 ]
  • [ 2406-90-8 ]
  • [ 659743-42-7 ]
  • 14
  • [ 2038-03-1 ]
  • [ 116668-47-4 ]
  • 6-amino-N-(2-morpholinoethyl)-2-naphthamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
54.6% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; [0071] Synthesis of(6-amino-N-(2-morpholinoethyl)-2-naphthamide): 6-amino-2- naphthoic acid (25 mg, 0.13 mmol), 2-morpholinoethanamine (69.5 mg, 70 mu, 0.53 mmol), and HBTU (98.5 mg, 0.26 mmol) were dissolved together in DCM. To the stirred solution, N,N-Diisopropylethylamine (16.77 mg, 22.6 mu, 0.13 mmol) was added drop wise. The reaction mixture was stirred at room temperature for 4 hours. The solvent was evaporated in rota vapour and the crude was obtained. The crude was purified by column chromatography using EA as eluent. Product was obtained as brown semi solid (21.24 mg, 54.6percent). 1H NMR (CDCI3, 300 MHz): delta 7.21 (d, IH, j= 3 Hz), 7.78-7.73 (m, 2H), 7.65 (d, j= 9 Hz, IH), 7.73- 7.00 (m, 2H), 3.79 (t, j= 4.5 Hz, 4H), 3.65 (q, j= 6.0 Hz, 2H), 2.68 (t, j= 6.0 Hz 2H), 2.58(t, j= 4.5 Hz, 4H). 13C NMR (75 MHz, CDCI3) delta 167.69, 145.89, 136.50, 130.38, 128.29, 127.52, 126.73, 125.94, 123.96, 118.81, 107.84, 66.81, 57.03, 53.27, 36.00. EI-MS (m/z): Calcd for C17H21N3O2, 299.16; found 300.0 (M+H).
  • 15
  • [ 2038-03-1 ]
  • [ 116668-47-4 ]
  • (9H-fluoren-9-yl)methyl(5-azido-1-((6-((2-morpholinoethyl)carbamoyl)naphthalen-2-yl)amino)-1-oxopentan-2-yl)carbamate [ No CAS ]
  • 16
  • [ 2038-03-1 ]
  • [ 50-00-0 ]
  • [ 24782-43-2 ]
  • 3-((2-morpholinoethylamino)methyl)-4-hydroxyquinoline-2-carboxylic acid dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% 4-Hydroxyquinoline-2-carboxylic acid ethyl ester (A, 326 mg, 1.5 mmol), 2- morpholinoethylamine (260 mg, 2.0 mmol), and formalin (22 %, 410 mg, 3.0 mmol) were placed in a 50 ml round bottom flask. The mixture was refluxed in 30 ml 1 ,4-dioxane for 5hours. After the evaporation of the solvent the residue was dissolved into 40 ml water, and extracted with 3x30 ml dichloromethane. The collected organic phase was dried (Na2SO4), the solvent was removed by evaporation, and the residue was crystallized from nhexane:EtOAc mixture.For the isolation of the hydrochloride salt compound 1 was taken into 15 ml EtOH,and 0.15 ml (1.0 mmol) HC1/EtOH (22%) solution was added to the mixture. The solvent wasremoved by evaporation, and the residue was crystallized from 10 ml Et20.Yield: 473 mg (78%); M.p. 300-303 C. ?H NMR (D20); 3.11-3.42 (2H, m); 3.54 (2H, t, J =5.6 Hz); 3.52-3.87 (4H, m); 4.01-4.20 (4H, m); 4.33 (2H, s); 7.43 (1H, t, J = 7.7 Hz); 7.57(1H, d, J 7.8 Hz); 7.72 (1H, t, J = 8.1 Hz); 8.04 (1H, d, J = 8.7 Hz)
  • 17
  • [ 2038-03-1 ]
  • [ 120085-99-6 ]
  • 2,9-bis{4-[(2-morpholinoethyl)iminomethyl]phenyl}-1,10-phenanthroline [ No CAS ]
  • 18
  • [ 2038-03-1 ]
  • [ 68302-57-8 ]
  • 2-amino-7-isopropyl-N-(2-morpholinoethyl)-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16.0h; Similar reaction of <strong>[68302-57-8]amlexanox</strong> (1; 200 mg, 0.67 mmol), 4-(2-aminoethyl)morpholine (131 mg, 1.0 mmol), EDC hydrochloride (192 mg, 1.0 mmol), HOBt(109 mg, 0.81 mmol), DIEA (260 mg, 2.0 mmol) and DMF (4 mL) followed by workup andpurification (elution with 3-5% MeOH in DCM) as described for 5c above gave 5d (123 mg,45%) as solid. 1H NMR (500 MHz, chloroform-d) delta 8.65 (s, 1H), 8.10 (d, J = 2.3 Hz, 1H), 7.59(dd, J = 8.6, 2.3 Hz, 1H), 7.44 (d, J = 8.5 Hz, 1H), 6.92 (br s, 1H), 3.77 (t, J = 4.6 Hz, 4H), 3.55(q, J = 5.6 Hz, 2H), 3.05 (p, J = 6.9 Hz, 1H), 2.64 (t, J = 6.0 Hz, 2H), 2.54 (d, J = 4.7 Hz, 4H),1.32 (d, J = 6.9 Hz, 6H). MS m/z 411.1 (M+H)+. HPLC 99%.
  • 19
  • [ 2038-03-1 ]
  • [ 97-08-5 ]
  • 4-chloro-N-(2-morpholinoethyl)-3-nitrobenzenesulfonamide [ No CAS ]
  • 20
  • [ 2038-03-1 ]
  • [ 207399-07-3 ]
  • C42H57N4O(1+)*I(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
20% In acetonitrile; at 50 - 80℃;Inert atmosphere; IR780 and 4-(aminoethyl)-morpholine are dissolved in 50 to 100 mL of anhydrous acetonitrile in a ratio of 1:2, and reacted at 50 to 80 C for 6 to 10 hours under a N 2 atmosphere.After the reaction is cooled, the solvent is distilled off under reduced pressure;Step 2: The product obtained by evaporating the above solvent is passed through a silica gel column, and eluted with a gradient of methanol:methylene chloride from 0:100 to 1:20 to obtain L1, the yield is 15-20%.The melting point is 86.7 to 87.3 C.
15.2% In acetonitrile; at 60℃;Inert atmosphere; <strong>[207399-07-3]IR-780</strong> (0.0834 g,0.125 mmol) and 4-(2-aminoethyl)morpholine (0.0325 g,0.25 mmol) were dissolved in anhydrous MeCN(50 mL), then heated to 60 oC under N2 protection. After the reaction was completed, the reaction system was cooled to 25 oC, and concentrated under reduced pressure. The red solid (L1) was obtained by silica gel column chromatography with methanol/dichloromethane(v:v) from 0:100 to1:20. Yield 15.2%, m.p 86.7-87.3 oC; 1H NMR (DMSO-d6, 400 MHz), (ppm): δ 8.15 (s,1H), 7.59-7.62 (d,J 12.7 Hz,2H),7.46-7.48 (d,J 6.5 Hz,2H),7.27-7.31 (t, J 6.6 Hz, 2H), 7.15-7.17 (d,J 7.2 Hz,2H),7.06-7.07 (d,J 6.5 Hz,2H), 5.78-5.81 (d,J 12.4 Hz,1H),3.94 (s,4H), 3.80 (s,2H), 3.61 (s,4H), 2.64 (s,2H), 2.43(s, 2H), 1.70-1.73 (m, 6H),1.61 (s,12H),0.94-0.95 (d,J 6.3 Hz, 6H);13C NMR (DMSO-d6, 100 MHz), (ppm): δ 168.38,166.80,143.10,139.60,137.52,128.17, 122.38,122.12, 121.80,119.46,118.02,109.21, 94.32,73.70, 66.09,53.07,29.85,28.47,24.85,21.27,19.68,11.30. FT-IR (KBr,4000 -400 cm -1) : 3427,3129,2962,2926,1524,1485,1455,1399,1384,1345, 1319,1254, 1200, 1174, 1113,1051,1019, 924,800,716; HRMS (ESI-MS) Calcd for C42H57N4O[M] 633.4532, found 633.4533. L2 was synthesized in a similar manner from 4-(3-aminopropyl)morpholine. Red solid, yield 14.3%.m.p 90.1-91.2 oC. 1H NMR(DMSO-d6, 400 MHz), (ppm): δ 8.58 (s,1H),7.57-7.61 (d,J 12.8 Hz,2H),7.45-7.47 (d, J 7.2 Hz,2H), 7.27-7.31 (t, J 7.6 Hz,2H),7.15-7.17 (d, J 7.8 Hz, 2H), 7.03-7.07 (t, J 7.3 Hz,2H),5.77-5.80 (d,J 12.6 Hz,1H),3.93 (s,4H),3.77 (s,2H),3.55 (s,4H), 3.39(s,12H),2.35 (s,4H), 1.68-1.73 (dd, J 13.3, 6.5 Hz,6H), 1.60(s,12H),0.92-0.96 (t, J 7.3 Hz,6H); 13C NMR (DMSO-d6, 100 MHz), (ppm): δ 169.02,166.65, 143.12, 139.71,137.66,128.15,122.30,122.10,119.72,109.14, 94.23,66.12,47.13,28.43,24.95,21.32,19.67,11.31;FT-IR (KBr, 4000-400 cm -1):3428,3131,2961, 2926,2869, 2811,1525,1485,1455,1384,1290,1199,1172,1172,1114,1051,1019,919,800,716. HRMS (ESI-MS) Calcd for C43H60N4O[M] 647.4689, found 647.4682.
 

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Technical Information

Categories

Related Functional Groups of
[ 2038-03-1 ]

Amines

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A141037 [108302-54-1]

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[ 2038-03-1 ]

Morpholines

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