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Chemical Structure| 438056-69-0

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Product Details of [ 438056-69-0 ]

CAS No. :438056-69-0
Formula : C10H12N2O2
M.W : 192.21
SMILES Code : NC1=CC=C(C=C1)N2CCOCC2=O
MDL No. :MFCD08236742
InChI Key :MHCRLDZZHOVFEE-UHFFFAOYSA-N
Pubchem ID :11194854

Safety of [ 438056-69-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 438056-69-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 56.77
TPSA ?

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

55.56 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.56
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

0.26
Log Po/w (WLOGP)?

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

0.26
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.

0.29
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

0.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.65

Water Solubility

Log S (ESOL):?

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

-1.45
Solubility 6.87 mg/ml ; 0.0358 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.

-0.99
Solubility 19.8 mg/ml ; 0.103 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

-2.12
Solubility 1.47 mg/ml ; 0.00766 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.

-7.29 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.

1.0 alert
Brenk?

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

1.0 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)

1.56

Application In Synthesis of [ 438056-69-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 438056-69-0 ]
  • Downstream synthetic route of [ 438056-69-0 ]

[ 438056-69-0 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 161596-47-0 ]
  • [ 438056-69-0 ]
  • [ 446292-07-5 ]
YieldReaction ConditionsOperation in experiment
92% at 65 - 70℃; for 32 h; 4-(4-aminophenyl)morpholinone 100 gm, 0.5202 moles and (S)-(+)glycidyl phthalimide 106.6 gm ( 0.5246 moles) was charged to the mixture of, methanol and water 1000 ml (9: 1) and heated to 65°C-70°C. Continued stirring for next 20 hrs at 65°C-70°C. Add second lot of S)-(+)glycidyl phthalimide 10.6 gm (0.05246 moles) and 200 ml (9: 1) methanol water mixture and stir for next 12 hrs. Cooled the reaction mass to 25°C-30°C and filter the slurry on Buckner funnel, suck dried well. Wet cake washed with 100 ml mixture of methanol and water (9: 1). The solid obtained was dried at 50°C to 55°C to get 190 gm compound of Formula-3 as dry material. Yield-92percent
92% for 10 h; Reflux Add 4-(4-aminophenyl)morphin-3-one (192.2 g, 1 mol) to a 1000 ml three-necked flask,2-(2-chloroethoxy)propane(203.2 g, 1 mol), 790 ml of ethanol, stirring was started, the temperature was raised to reflux, and the TLC was detected. It was found that the starting material disappeared after 10 hours of reaction, and the reaction was completed and lowered to room temperature. After suction filtration, 100 ml of ethanol was washed three times, and the compound (4) was dried to obtain 363.78 g, the yield was 92percent, and the HPLC detection was 98.67percent.
89.7% for 14 h; Reflux A mixture of 5.68 g(27.9 mmol) of compound V was added compound VI 5.35 g (27.9 mmol) was suspended in 140 ml of 1/9 water - ethanol, stirring reflux for 14 hours, cooled to 20 °C, filter, filter the filter cake with ethanol 3 times. 65-70 °C under reduced pressure, to obtain 9.9 g of the compound of the formula (I) (yield: 89.7percent ) HPLC content 98.5percent (normalization).
87.5% at 25℃; for 24 h; Reflux In a four neck round bottom flask charged Isopropyl alcohol (135 ml), 4-(4-aminophenyl) morpholin-3-one (10 g), 2-[(2s)-oxiran-2yl methyl]-lH-isoindole-l,3(2H) dione ((11.6 g) and water (15 ml) at 25 to 30°C. Slowly heated the reaction mixture to reflux and maintained for 24 h at reflux temperature. Reaction mass is cooled to 25 to 30°C after completion of the reaction. Reaction mass then maintained at 25 to 30°C for 30 minutes. Finally obtained solid is filtered off and washed by isopropyl alcohol (25 ml) Yield 87.5percent
87.5% for 24 h; Reflux To a 2 litre 4 neck RBF, charge Methanol (1500 ml), 4-(4-aminophenyl)-3-morpholinone Compound (VI), (100 gms), (S)-Glycidyl Phthalimide Compound (V), (127 gms). Reflux the reaction mass for 24 hrs. Cool the reaction mass at 25-30°C and filter. Wash the residue with Methanol (50 ml). Dry the solid at 45-50°C under vacuum. Dry Wt: 180 gms (Theoretical yield: 87.50percent); Purity: 98.20percent
82.6% Reflux A suspension of 4-(4-aminophenyl)morpholin-3-one (100 gm) and 2-[(2S)-oxiran-2-ylmethyl}-1H-isoindole-1,3(2H)-dione (116.2 gm) in isopropyl alcohol and water mixture (l700ml :300 ml) is refluxed for 25-30 h. The precipitated solid is filtered off, washed with isopropyl alcohol (100 ml) to obtain solid, which is then dried under vacuum at 50 to 55 °C for 4 to5 hr to obtain 2-[(2R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl]-1 H-isoindole-1,3(2H)-dione. [Yield = 170 gm (82.6percent); Purity (H PLC) = 95.0 percent]
82.6% Reflux A suspension of 4-(4-aminophenyl)morpholin-3-one (100 gm) and 2-[(2S)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-dione (116.2 gm) in isopropyl alcohol and water mixture (1700 ml:300 ml) is refluxed for 25-30 h.
The precipitated solid is filtered off, washed with isopropyl alcohol (100 ml) to obtain solid, which is then dried under vacuum at 50 to 55° C. for 4 to 5 hr to obtain 2-[(2R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl]-1H-isoindole-1,3(2H)-dione. [Yield=170 gm (82.6percent); Purity (HPLC)=95.0percent]
82.7% at 0 - 60℃; for 20 h; Large scale This example relates to the preparation of 2-{(fl)-2-hydroxy-3-[4-(3-oxo- morpholine-4-yl)-phenylamino]-propyl}isoindol-1 ,3-dione, step a) of the process. 10.0 kg of 4-(4-aminophenyl)morpholine-3-one, 13.0 kg of (S)-(+)-N-(2,3- epoxypropyl)phthalimide and 170 kg of methanol are loaded into a reactor as a single solvent. The mass is heated to around 60 °C and maintained at this temperature for 20 hours, then cooled to 0-10 °C. There is precipitation of the desired product, which is filtered and washed with 30.0 kg of methanol. The product obtained is oven-dried, obtaining 17.0 kg of the desired compound (III), with a reaction yield equal to 82.7percent.
81.4% at 20 - 60℃; for 36 h; 1173 g of 2-[(2S)-2-oxiranylmethyl]-1H-isoindole-1,3(2H)dione (II) and 4-(4-aminophenyl)-3-morpholinone (III) are mixed at 20° C. with 6.7 l of water and 14.4 l of ethanol.
The suspension is heated to 58 to 60° C., and the resulting solution is stirred for 36 hours.
After 2 hours, 5 g of crystalline 2-((2R)-2-hydroxy-3-[4-(3-oxo-4-morpholinyl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione (V) are added to the reaction mixture, after which the product starts to crystallize.
After cooling to 26° C., the precipitated reaction product is filtered off with suction, washed with ethanol and then dried.
Yield: 1522 g; equivalent to 81.4percent of theory.
Melting point: 215° C.
80.68% at 80℃; for 9 h; 238.50 g (1.174 mol) of 2-[(2S)-2-oxiranylmethyl]-1 H-isoindole-1 , 3(2H)-dione (I), 150 g (0.781 mol) of 4-(4-amino phenyl)-3-morpholinone and 3L of ethanol were charged in a 5L flask and the reaction mass was heated at 80 °C for 9 hours. Afterwards the reaction mass was cooled down to 30 °C, and the resulting solid was filtered off and dried under vacuum at 70 °C.Yield: 249 g. Molar yield: 80.68percent. HPLC purity 96.90percent. M.P.: 214 °C. Specific Optical Rotation (S.O.R.): [a ]D25 = +6.24° (c = 1 ,DMSO)
75.4% With water In ethanol at 60℃; for 36 h; Industry scale A suspension of (S) -2- (oxiran-2-ylmethyl) isoindoline-1, 3-dione (4.5kg, 1.22eq) and 4- (4-aminophenyl) morpholin-3-one (3.286kg , 17.088 mol) in ethanol/water (42L/16kg), was heated at 60 0C for 36 hours. It was further cooled to room temperature, the precipitate was filtered, and dried in vacuum. An amount of 5.1 kg of the product was obtained (Yield 75,4percent).
203 g at 80℃; for 8 h; To 100 gm (0.5208 moles) of 4-(4-Aminophenyl) morpholin-3-one (III) in 2500 ml purified water, 185 gm (0.9104 moles) of (S)- Glycidyl Phthalimide (IV) and 1000ml purified water0 was charged and the reaction mixture was heated to 80 °C for 8 hours. The precipitated products was filtered and washed with purified water. The product was dried under vacuum at 60°C to 65°C for 24 hours. Dried weight = 203 gm

References: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 19, p. 5900 - 5908.
[2] Patent: WO2018/127762, 2018, A1, . Location in patent: Page/Page column 12.
[3] Patent: CN108164519, 2018, A, . Location in patent: Paragraph 0014; 0015; 0016; 0017.
[4] Patent: CN106588905, 2017, A, . Location in patent: Paragraph 0044; 0046-0047.
[5] Patent: WO2014/102820, 2014, A2, . Location in patent: Paragraph 047.
[6] Patent: WO2016/199027, 2016, A1, . Location in patent: Page/Page column 18.
[7] Patent: WO2013/121436, 2013, A2, . Location in patent: Page/Page column 26.
[8] Patent: US2015/11756, 2015, A1, . Location in patent: Paragraph 0117.
[9] Patent: WO2015/198259, 2015, A1, . Location in patent: Page/Page column 6.
[10] Patent: US2005/182055, 2005, A1, . Location in patent: Page/Page column 1; 3.
[11] Patent: WO2005/68456, 2005, A1, . Location in patent: Page/Page column 7.
[12] Patent: WO2013/53739, 2013, A1, . Location in patent: Page/Page column 31.
[13] Patent: WO2011/12321, 2011, A1, . Location in patent: Page/Page column 31.
[14] Patent: WO2013/98833, 2013, A2, . Location in patent: Page/Page column 41.
[15] Patent: US2014/378682, 2014, A1, . Location in patent: Paragraph 0209; 0210.
[16] Patent: WO2016/30669, 2016, A1, . Location in patent: Page/Page column 28.
  • 2
  • [ 5455-98-1 ]
  • [ 438056-69-0 ]
  • [ 446292-07-5 ]
References: [1] Patent: US2008/306070, 2008, A1, .
[2] Patent: US2010/120718, 2010, A1, .
[3] Patent: US2010/160301, 2010, A1, .
  • 3
  • [ 438056-69-0 ]
  • [ 446292-07-5 ]
References: [1] Patent: WO2012/32533, 2012, A2, .
[2] Patent: WO2012/32533, 2012, A2, .
[3] Patent: WO2012/51692, 2012, A1, .
[4] Patent: CN104974105, 2017, B, .
[5] Patent: CN104974148, 2017, B, .
[6] Patent: CN103951661, 2017, B, .
[7] Patent: CN104974149, 2018, B, .
  • 4
  • [ 799012-78-5 ]
  • [ 438056-69-0 ]
  • [ 721401-53-2 ]
YieldReaction ConditionsOperation in experiment
86% With magnesium(II) perchlorate In acetonitrile at 25 - 30℃; for 3 h; 4-(4-Aminophenyl)morpholin-3-one (Formula V; 50 g) was dissolved in acetonitnle (500 mL) at 25°C to 30°C. 5-Chloro-N-[(2S)-2-oxiranylmethylj-2- thiophenecarboxamide (from Example 4; Formula IV; 58 g) and magnesium perchlorate (12.5 g) were added to the reaction mixture, and the reaction mixture was stirred at 25°C to 30°C for 3 hours. Toluene (500 mL) and aqueous sodium chloride solution (20percent, 500 mL) were added slowly to the reaction mixture, and the reaction mixture was stirred for 2 hours. The solid was filtered, washed with water (100 mL), and suck dried. The solid was dried at 55°C to 60°C under vacuum for S hours to obtain cmde S-chloro-N-((2R)-2- hydroxy-3 - { [4-(3-oxo-4-morpholinyl)-phenyljamino }propyl)-2-thiophenecarboxamide (90 g, 84.5percent). The cmde material (50 g) was stirred with denatured spirit (500 mL) at 50°C to 55°C for 45 minutes. The reaction mixture was cooled to 25°C to 30°C, filtered, and washed with denatured spirit (100 mL). The solid obtained was suck dried, and then further dried at 55°C to 60°C for 12 hours to obtain 5-chloro-N-((2R)-2-hydroxy-3-[4-(3- oxo-4-morpholinyl)-phenyljamino }propyl)-2-thiophenecarboxamide.Yield: 86percentHPLC Purity: 99.88percent
77% at 70 - 75℃; for 4 h; 4-Aminophenyl morpholinone-3-one (Formula VI - 1.76 g, 0.00914 moles) was added to a solution of 5-chloro-N-[(2S)-oxiran-2-ylmethyl]thiophene-2-carboxamide (Formula V - 2 g, 0.00919 moles) in ethanol (31.5 mL) and deionized water (3.5 mL) at ambient temperature. The mixture was allowed to heat to 70°C to 75°C and stirred for 4 hours at 70°C to 75°C. The reaction mixture was cooled to 15°C, and the slurry obtained was stirred for 1 hour at 15°C to 20°C. The slurry was filtered and suck dried. The wet solid was dried under vacuum at 40°C to 45°C.
62% at 75℃; Step a): 5-Chloro-N-((2R)-2-hydroxy-3-[4-(3-oxo-4-morpholinyl)phenyl]amino}-propyl)-2-thiophenecarboxamide; 6.18 g (32 mmol) of 4-(4-aminophenyl)morpholin-3-one (Example 2A) and 7.00 g (32 mmol) of 5-chloro-N-[(2S)-2-oxiranylmethyl]-2-thiophenecarboxamide (Example 3A) are suspended in 130 ml of ethanol/water (9:1) and stirred at 75° C. overnight (formation of a solution). The solution is cooled in an ice-bath, and the resulting white precipitate is filtered off, washed with diethyl ether and dried under high vacuum. This gives 4.98 g of the title compound. Concentration of the mother liquor, another addition of 3.5 g (16 mmol) of 5-chloro-N-[(2S)-2-oxiranylmethyl]-2-thiophenecarboxamide in 50 ml of ethanol/water (9:1), more stirring at 75° C. overnight and filtration of the precipitate obtained after cooling in an ice-bath gives another 3.44 g of the title compound.Yield: 8.42 g in total (62percent of theory)LC-MS (method 1): Rt=1.46 min;MS (ESIpos): m/z=410 [M+H]+;1H-NMR (300 MHz, DMSO-d6): δ=8.60 (t, 1H), 7.69 (d, 1H), 7.18 (d, 1H), 7.02 (d, 2H), 6.59 (d, 2H), 5.65 (t, 1H), 5.08 (d, 1H), 4.13 (s, 2H), 3.91 (dd, 2H), 3.87-3.74 (m, 1H), 3.59 (m, 2H), 3.30-2.90 (m, 4H).
References: [1] Patent: WO2015/11617, 2015, A1, . Location in patent: Page/Page column 10; 11.
[2] Patent: WO2013/156936, 2013, A1, . Location in patent: Page/Page column 17.
[3] Patent: US2010/48548, 2010, A1, . Location in patent: Page/Page column 10.
  • 5
  • [ 348626-26-6 ]
  • [ 438056-69-0 ]
  • [ 721401-53-2 ]
YieldReaction ConditionsOperation in experiment
92% at 20 - 60℃; 500 mg (2.6 mmol) of 4-(4-aminophenyl)morpholin-3-one are dissolved in 10 ml of THF and, at RT, 679.47 mg (3.1 mmol) of 5-chloro-N-[(2S)-2-oxiranylmethyl]-2-thiophenecarboxamide and 161.34 mg (0.3 mmol) of ytterbium(III) trifluoromethanesulfonate are added. The solution is stirred at 60° C. overnight. The precipitated white product is filtered off, washed with THF and dried under high vacuum. 574 mg (54percent of theory) of the title compound are obtained. The filtrate is concentrated and the residue is purified by preparative HPLC (column: YMC gel ODS-AQ S-11 μm; mobile phase: water/acetonitrile, gradient 90:10-->5:95). A further 402 mg (38percent of theory) of the desired product are obtained in this way. Yield: total 976 mg (92percent of theory) LC-MS (method 1): Rt=1.67 min. MS (ESIpos): m/z=410 [M+H]+ 1H-NMR (200 MHz, DMSO-d6): δ=8.62 (t, 1H), 7.68 (d, 1H), 7.18 (d, 1H), 7.02 (d, 2H), 6.59 (d, 2H), 5.66 (t, 1H), 5.09 (d, 1H), 4.13 (s, 2H), 3.96-3.88 (m, 2H), 3.86-3.74 (m, 1H), 3.64-3.55 (m, 1H), 3.30-2.90 (m, 2H).
76% With magnesium(II) perchlorate In acetone at 50℃; for 18 h; Inert atmosphere 1 g of 4-(4-aminophenyl)-3-morpholinone prepared in Example 4,1.36 g of 5-chloro-N-(2-oxiranylmethyl)-2-thiophenecarboxamide prepared in Example 7 was charged and placed in a reaction vessel.Then add 200g of dried magnesium perchlorate, then add 10L of acetone.Under nitrogen protection, react at 50 ° C for 18 h to obtain 5-chlorothiophene-2-{(R)-2-hydroxy-3-[4-(3-Oxo-4-morpholinyl)phenylamino]-propyl}amide, separated by column chromatographyObtained a pale yellow solid,The yield was 76percent.
References: [1] Patent: US2007/66615, 2007, A1, . Location in patent: Page/Page column 15-16.
[2] Patent: CN104788444, 2018, B, . Location in patent: Paragraph 0056; 0057; 0058.
  • 6
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  • [ 438056-69-0 ]
  • [ 721401-53-2 ]
YieldReaction ConditionsOperation in experiment
76% With 2,3,4-lutidine In ethanol; toluene; butan-1-ol at 20 - 105℃; Example 4: 5-Chlorothiophen-2-carboxylic acid-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]-propyl}amide To a suspension of 2.55g of 4-[4-[(5R)-5-(chlorothiopheno-2-carboxylic acid ((S)-2-hydroxy-3-tosyloxy)-propyl)-amide (MW = 389.88; 1 eq.) in 15mL toluene were added 1.22 g of 4-(4-amino-phenyl)-morpholin-3-one (MW = 190.22; 1 eq.), 0.73g collidine (MW = 121.18; 0.9 eq.) and 0.29mL ethanol. The reaction mixture was heated to 105°C and stirred at this temperature for 3 hours. Then 2.5mL of n-butanol were added and the mixture was cooled to 22°C. After stirring for at least 1 hour at ambient temperature the product was isolated by filtration and washed with toluene and water. The wet product was dried at 30°C in vacuo to yield 2.00g of the title compound (76percent by theory).
76% With collidine In ethanol; toluene at 105℃; for 3 h; To a suspension of 2.55g of 4-[4-[(5R)-5-(chlorothiopheno-2-carboxylic acid ((S)-2-hydroxy- 3-tosyloxy)-propyl)-amide (MW = 389.88; 1 eq.) in 15mL toluene were added 1.22 g of 4-(4- amino-phenyl)-morpholin-3-one (MW = 190.22; 1 eq.), 0.73g collidine (MW = 121.18; 0.9 eq.) and 0.29ml_ ethanol. The reaction mixture was heated to 105°C and stirred at this temperature for 3 hours. Then 2.5mL of n-butanol were added and the mixture was cooled to 22°C. After stirring for at least 1 hour at ambient temperature the product was isolated by filtration and washed with toluene and water. The wet product was dried at 30°C in vacuo to yield 2.00g of the title compound (76percent by theory).
References: [1] Patent: EP2354128, 2011, A1, . Location in patent: Page/Page column 15; 16.
[2] Patent: WO2011/98501, 2011, A1, . Location in patent: Page/Page column 25; 26.
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References: [1] Patent: WO2004/60887, 2004, A1, . Location in patent: Page/Page column 8; 10.
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References: [1] Patent: CN104817550, 2017, B, . Location in patent: Paragraph 0050.
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  • [ 71-36-3 ]
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References: [1] Patent: US2007/149522, 2007, A1, .
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References: [1] Patent: EP2354128, 2011, A1, .
[2] Patent: CN104860904, 2016, B, .
 

Historical Records

Technical Information

• Acyl Group Substitution • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • Grignard Reaction • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

Related Functional Groups of
[ 438056-69-0 ]

Aryls

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4-Phenylmorpholin-3-one

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Related Parent Nucleus of
[ 438056-69-0 ]

Morpholines

Chemical Structure| 29518-11-4

A183983 [29518-11-4]

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