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Chemical Structure| 134997-74-3 Chemical Structure| 134997-74-3

Structure of 134997-74-3

Chemical Structure| 134997-74-3

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Product Details of [ 134997-74-3 ]

CAS No. :134997-74-3
Formula : C9H6N2O2
M.W : 174.16
SMILES Code : N#CC1=CC=C(C(N2)=C1)OCC2=O
MDL No. :MFCD20039908
InChI Key :WCBILQWUWLALFZ-UHFFFAOYSA-N
Pubchem ID :10654813

Safety of [ 134997-74-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 134997-74-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 47.98
TPSA ?

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

62.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.37
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

0.59
Log Po/w (WLOGP)?

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

0.32
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.

-0.1
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

1.45
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.73

Water Solubility

Log S (ESOL):?

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

-1.63
Solubility 4.05 mg/ml ; 0.0233 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.

-1.47
Solubility 5.93 mg/ml ; 0.034 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

-2.71
Solubility 0.338 mg/ml ; 0.00194 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

Yes
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.

-6.94 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)

1.9

Application In Synthesis of [ 134997-74-3 ]

* 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 [ 134997-74-3 ]

[ 134997-74-3 ] Synthesis Path-Downstream   1~35

  • 3
  • [ 134997-74-3 ]
  • [ 2675-89-0 ]
  • [ 221225-63-4 ]
  • 9
  • [ 134997-74-3 ]
  • 2-(6-cyano-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-<i>N</i>-methyl-acetamide [ No CAS ]
  • 10
  • [ 134997-74-3 ]
  • 3-(6-cyano-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-<i>N</i>,<i>N</i>-dimethyl-propionamide [ No CAS ]
  • 11
  • [ 134997-74-3 ]
  • 2-[6-(4,5-dihydro-thiazol-2-yl)-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl]-<i>N</i>-methyl-acetamide [ No CAS ]
  • 12
  • [ 134997-74-3 ]
  • 4-[6-(4,5-dihydro-thiazol-2-yl)-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl]-<i>N</i>,<i>N</i>-dimethyl-butyramide [ No CAS ]
  • 14
  • [ 134997-74-3 ]
  • 3-[6-(4,5-dihydro-thiazol-2-yl)-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl]-propionic acid ethyl ester [ No CAS ]
  • 15
  • [ 134997-74-3 ]
  • 2-[6-(4,5-Dihydro-thiazol-2-yl)-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl]-N,N-dimethyl-acetamide [ No CAS ]
  • 16
  • [ 14543-43-2 ]
  • [ 79-04-9 ]
  • [ 134997-74-3 ]
YieldReaction ConditionsOperation in experiment
60% With dmap; triethylamine; In dichloromethane; at 0℃; for 24h;Heating / reflux; Chloroacetyl chloride (3.12 ml, 38 mmol) was added dropwise to a solution of 2-amino-4-cyanophenol (4.96 g, 37 mmol), triethylamine (10.98 ml, 78 mmol) and 4-(dimethylamino)pyridine (0.09 g, 0.74 mmol) in dry dichloromethane (40 ml) maintained at 0 C. The solution refluxed for 24 h. The reaction mixture was cooled, and the organic layer was washed with phosphoric acid (0.5 M), saturated sodium bicarbonate, water and brine, then dried with anhydrous magnesium sulfate. The organic layer was filtered, then evaporated to dryness. The residue was recrystalized from ethanol to afford 3.9 g (60%) of the titled compound. (mp 243-245 C.).
  • 17
  • [ 7652-29-1 ]
  • [ 544-92-3 ]
  • [ 134997-74-3 ]
YieldReaction ConditionsOperation in experiment
62% In 1-methyl-pyrrolidin-2-one; at 250℃; for 20h; A suspension of commercially available 6-chloro-4H-benzo[1,4]oxazin-3-one (1.83 g) and copper(I) cyanide (1.81 g) in N-methyl-pyrrolidin-2-one (40 mL) was placed in a preheated oil bath (250 C.). After stirring at this temperature for 20 h, the mixture was cooled to room temperature, diluted with water (200 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with water (2×200 mL) and brine (200 mL), dried (MgSO4), filtered and concentrated. The remaining residue was purified by flash chromatography (silica, cyclohexane/ethyl acetate) to afford the title compound (1.08 g; 62%). [MH]+=175.
24% In N-methyl-pirrolidine-2-one; at 250℃; A suspension of commercially available 6-chloro-4H-benzo[l,4]oxazin-3-one (3.2 g) and CuCN (2.9 g) in dry N-methyl-pyrrolidin-2-one (15 mL) was placed in a preheated oil bath (~250C). After stirring at this temperature overnight, the mixture was concentrated, diluted with H2O (200 mL) and extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with H2O (2 x 200 mL) and saturated aqueous NaCl (200 mL), dried (MgSO4), filtered and concentrated. The remaining residue crystallized from EtOAc/toluene to afford the title compound as a tan solid (720 mg, 24%). [MH]+ = 175.
24% In 1-methyl-pyrrolidin-2-one; at 250℃; Preparative Example 6; Step A; A solution of commercially available 6-chloro-4H-benzo[1,4]oxazin-3-one (3.2 g) and CuCN (2.9 g) in anhydrous N-methylpyrrolidone (15 mL) was stirred overnight in a pressure tube at 250 C. and then evaporated under reduced pressure. The residue was diluted with ethyl acetate, filtered and the remaining liquid was washed subsequently with 10% citric acid, saturated sodium hydrogen carbonate and brine, dried (MgSO4) and concentrated. Crystallization from toluene/ethyl acetate afforded the intermediate (720 mg; 24%) as a tan solid. [MH]+=175.
  • 18
  • [ 14543-43-2 ]
  • [ 598-21-0 ]
  • [ 134997-74-3 ]
YieldReaction ConditionsOperation in experiment
69% With sodium hydrogencarbonate; In chloroform; water; at 0 - 20℃; Intermediate 60: 3-Oxo-3,4-dihydro-2H-l,4-benzoxazine-6-carbonitrile The title compound was prepared similarly to literature procedure (Caliendo, G; et. al.;Bioorg. Med. Chem. Lett, 2002, K), 2663), but in one step. Commercially available 3-amino- 4-hydroxybenzonitrile (2.5 g, 18.6 mmol) was dissolved in chloroform (300 mL) and saturated sodium bicarbonate (90 mL). The biphasic reaction mixture was cooled to 00C and bromoacetyl bromide (2.4 mL, 28 mmol) was added dropwise. The reaction was stirred overnight at room temperature. The layers were separated and the aqueous layer was filtered to yield the desired product as a tan solid, 2.3 g (69%). MS (ES): 175.11 (MH+) for C9H6N2O21H-NMR HJMSO-(U delta: 4.70 (s, 2H); 7.11 (d, IH); 7.19 (d, IH); 7.40 (m, IH); 10.98 (bs, IH).;
  • 19
  • [ 67-56-1 ]
  • [ 134997-74-3 ]
  • [ 604756-32-3 ]
YieldReaction ConditionsOperation in experiment
40% With chloro-trimethyl-silane;Heating / reflux; Intermediate 86: Methyl 3-oxo-3,4-dihvdro-2H-l,4-benzoxazine-6-carboxylate3-Oxo-3,4-dihydro-2H-l,4-benzoxazine-6-carbonitrile (Intermediate 60) was heated with chlorotrimethylsilane in methanol according to literature procedure ( Fen-tair Luo et al. Tetrahedron Letters, 3_9, 1998, page 9455-9456). After removal of volatiles, the product was EPO <DP n="101"/>purified by chromatography on silica gel with methanol/dichloromethane (1:20) and obtained as off white solid, 40% yield.MS QBSV 208 (MH+) for C)0H9NO41H-NMR (DMSO-phi delta: 3.80 (s, 3H); 4.67 (s, 2H); 7.03 (d, IH); 7.50 (d, IH); 7.55 (dd, IH); 10.99 (s, IH).
  • 21
  • [ 134997-74-3 ]
  • [ 74-88-4 ]
  • [ 916210-08-7 ]
YieldReaction ConditionsOperation in experiment
52% With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h; The title compound from the Preparative Example 20, Step A (549 mg) was dissolved in dry DMF (7 mL) and cooled to 0C. An excess of NaH and methyl iodide were added subsequently and the mixture was stirred for 2 h while warming to room temperature. The mixture was diluted with EtOAc, washed subsequently with IN aqueous HCl and saturated aqueous NaCl, dried (MgSO4), filtered, absorbed on silica and purified by chromatography (silica, cyclohexane/EtOAc) to afford the title compound as colorless needles (311 mg, 52%). [MH]+ = 189.
  • 22
  • [ 24424-99-5 ]
  • [ 134997-74-3 ]
  • [ 134997-81-2 ]
YieldReaction ConditionsOperation in experiment
88% Step B; To an ice cooled solution of the title compound from Step A above (5.6 g), di-tert-butyl dicarbonate (14.06 g) and NiCl2-OH2O (1.53 g) in MeOH, NaBH4 (8.51 g) was added in portions. The mixture was vigorously stirred for Ih at 0 C and Ih at room temperature. After the addition of diethylenetriamine (3.5 mL) the <n="74"/>mixture was concentrated, diluted with EtOAc, washed subsequently with IN HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl, dried (MgSO4), concentrated to afford the title compound as an off white solid (7.91 g, 88 %; M+Na+ = 397).
88% With sodium tetrahydroborate; nickel dichloride; In methanol; at 0 - 20℃; for 2h; Step B. To an ice cooled solution of the title compound from Step A above (5.6 g), di-tert-butyl dicarbonate (14.06 g) and NiCl2-OH2O (1.53 g) in MeOH, NaBH4 (8.51 g) was added in portions. The mixture was vigorously stirred for Ih at 0C and Ih at room temperature. After the addition of diethylenetriamine (3.5 mL) the mixture was concentrated, diluted with EtOAc, washed subsequently with IN HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl, dried (MgSO4), concentrated to afford the title compound as an off white solid (7.91 g, 88%). [M+Na]+ = 397.
With sodium tetrahydroborate; nickel dichloride; In methanol; at 0℃; for 6h; Step B; The intermediate from step A above (377 mg), di-tert-butyl dicarbonate (1.3 g) and nickel(II) chloride hexahydrate (50 mg) were dissolved in dry methanol (30 mL) and cooled to 0 C. Then sodium borohydride (500 mg) was added in portions and the ice bath removed. The mixture was vigorously stirred for 6 h, then diethylenetriamine (300 muL) was added and the mixture was concentrated to dryness. The residue was diluted with ethyl acetate, washed with 10% citric acid, saturated sodium hydrogen carbonate and brine, dried (MgSO4), concentrated and purified by column chromatography (silica, dichloromethane/methanol, 98:2) to afford the intermediate, which was stirred in hydrogen chloride (4M solution in dioxane; 12 mL) for 2 h and the evaporated to afford the title compound (214 mg; 41%) as a colourless solid. [M-Cl]+=179.
  • 23
  • [ 55197-32-5 ]
  • [ 134997-74-3 ]
YieldReaction ConditionsOperation in experiment
With ammonium chloride; zinc; In methanol; at 20℃; for 2h; 3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonitrile 24 mmol of 4-Hydroxy-3-nitrobenzonitrile were dissolved in DMF. 1.1 eq of Cs2CO3 were added and the reaction stirred at rt for 15 min. 1.5 eq of ethylbromo acetate were added and the reaction mixture heated to 50 C. for 2 h. The intermediate was isolated via extraction from ethylacetate/water. The organic layer was separated and dried over Na2SO4. After evaporation the resulting solid was redissolved in MeOH and sat. NH4Cl (1:1). 8 g of Zn powder were added and the suspension stirred at rt for 2 h. The solid was filtered off and the organic layer evaporated. Ethylacetate was added and the organic layer washed with sat. NaHCO3. The organic layer was separated again, dried over Na2SO4 and reduced resulting in a light brown solid. MS(ISO): 175.2 (MH+)
  • 24
  • [ 34619-03-9 ]
  • [ 134997-74-3 ]
  • [ 134997-81-2 ]
YieldReaction ConditionsOperation in experiment
88% With sodium tetrahydroborate;nickel(II) chloride hexahydrate; In methanol; at 0 - 20℃; for 2h; To an ice cooled solution of the title compound from Step A above (5.6 g), di-tert-butyl dicarbonate (14.06 g) and NiCl2-OH2O (1.53 g) in MeOH, NaBH4 (8.51 g) was added in portions. The mixture was vigorously stirred for Ih at O0C and Ih at room temperature. After the addition of diethylenetriamine (3.5 mL) the mixture was concentrated, diluted with EtOAc, washed subsequently with IN HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl, dried (MgSO4), concentrated to afford the title compound as an off-white solid (7.91 g, 88%). [M+Na]+ = 397.
  • 25
  • [ 24036-52-0 ]
  • [ 557-21-1 ]
  • [ 134997-74-3 ]
YieldReaction ConditionsOperation in experiment
89% With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; A degassed suspension of commercially available 6-Bromo-4H- benzo[l ,4]oxazin-3-one (8.39 g), Zn(CN)2 (3.46 g) and Pd(PPh3)4 (2.13 g) in DMF (70 mL) was stirred in a oil bath (80C) overnight. The mixture was cooled to room temperature and then poured into water (500 mL). The precipitate was collected by suction, air dried, washed with pentane, dissolved in CH2Cl2ZMeOH (1 : 1), filtered through an silica pad and concentrated to yield a yellow solid (5.68 g, 89%). [MH]+ = 175.
89% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; Step A; A degassed suspension of commercially available 6-Bromo-4H- benzo[l,4]oxazin-3-one (8.39 g), Zn(CN)2 (3.46 g) and Pd(PPh3)4 (2.13 g) in DMF (70 mL) was stirred in a oil bath (80 C) overnight. The mixture was cooled to room temperature and then poured into water (500 mL). The precipitate was collected by suction, air dried, washed with pentane, dissolved in CH2Cl2ZMeOH (1:1), filtered through an silica pad and concentrated to yield a yellow solid (5.68 ^ 89 0ZoJ MH+ = ITS).
89% tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; Step A. A degassed suspension of commercially available 6-Bromo-4H-benzo[l,4]oxazin-3-one (8.39 g), Zn(CN)2 (3.46 g) and Pd(PPh3)4 (2.13 g) in DMF (70 mL) was stirred in a oil bath (80 C) overnight. The mixture was cooled to room temperature and then poured into water (500 mL). The precipitate was collected by suction, air dried, washed with pentane, dissolved in CH2Cl2/Me0H (1:1), filtered through a silica pad and concentrated to yield a the title compound (5.68 g, 89%). [MH]+ = 175.
  • 26
  • 1-tert-butyl 3-methyl 4-{3-[(methylsulfonyl)oxy]propyl}piperidine-1,3-dicarboxylate [ No CAS ]
  • [ 134997-74-3 ]
  • 1-tert-butyl 3-methyl (cis)-4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-1,3-dicarboxylate [ No CAS ]
  • (trans)-1-tert-butyl 3-methyl 4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-1,3-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Intermediate 131: 1-fert-Butyl 3-methyl 4-r3-f6-cvano-3-oxo-2.3-dihydro-4H-L4- benzoxazin-4-yl)propyllpiperidine-13-dicarboxylateA solution of 3-oxo-3,4-dihydro-2H-l,4-benzoxazine-6-carbonitrile (Intermediate 60) ( 265 mg, 1.53 mmol) in dry dimethylformamide (DMF) (5 mL) was treated at O0C with sodium hydride (105 mg, 60% in oil, 2.63 mmol) and then stirred for 30 minutes at room temperature. A solution of l-f°^-butyl 3-methyl 4-{3-[(methylsulfonyl)oxy]propyl}piperidine-l,3-dicarboxylate in DMF (Intermediate 132, 0.31 mmol/ mL, 5 mL, 1.53 mmol) was then added and the resulting mixture was stirred at room temperature for 96 hours. The reaction was diluted with ethyl acetate and water. The aqueous layer was adjusted to pEta3 with IN HCl. The layers were separated. The aqueous phase was extracted once with ethyl acetate. The combined organic phases were washed four times with water, dried over magnesium sulfate and evaporated at reduced pressure. Chromatography on silica gel with (10 -35%) acetone in hexanes gave 445 mg (64 %) of the product as a white semi-solid (as a mixture of diastereomers). MS TES^): 458 (MH+) for C24H3iN3O61H NMR fCDCW) delta: 1.43 and 1.44 (two s, 9H); 1.47-1.9 (m, 7H); 2.56-2.83 (m, 2H); 2.94-3.2 (m, IH); 3.65 and 3.70 (two s, 3H); 3.76-3.99 (m, 2H); 4.02-4.21 (m, IH); 4.67 and 4.70 (two s, 2H); 7.04 (m, IH); 7.11 and 7.18 (two brs, IH); 7.30 (m, IH).
  • 27
  • C19H39NO6SSi [ No CAS ]
  • [ 134997-74-3 ]
  • [ 917344-13-9 ]
YieldReaction ConditionsOperation in experiment
Intermediate 186: fert-Butyl C2i?,5i?)-5-(rfer/-butyl('dimethyl')silyl1oxy)-2-r2-r6- cvano-3-oxo-213-dihydro-4H-l,4-benzoxazin-4-yl)ethyl1piperidine-l-carboxylateTo a solution of tert-bntyl (2i?,5i?)-5-[/er/-butyl(dimethyl)silyl]oxy}-2-(2- hydroxyethyl)piperidine-l -carboxylate (Intermediate 187, 1.27 g) in methylene chloride (15 mL) at 0 C were added diisopropylethylamine (1.2 mL) and methanesulfonyl chloride (0.50 mL). At the same time in a separate flask, to a solution of3-oxo-3,4-dihydro-2H-l,4- benzoxazine-6-carbonitrile (Intermediate 60) (0.66 g) in DMF (8 mL) at 0 0C was added 60% suspension in oil of NaH (0.25 g). After 30 minutes, the mesylate solution was diluted with methylene chloride, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated. This residue was dissolved in DMF (5 mL) and added to the sodium salt of Intermediate 60. The reaction was stirred over the weekend, diluted with ethyl acetate, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated to give the product.MS (ESD 516 (MH+) for C27H41N3O5Si
  • 29
  • [ 134997-74-3 ]
  • 3-oxo-4-[2-(4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]-oxazin-6-yl)methyl]amino}piperidin-1-yl)ethyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carbonitrile [ No CAS ]
  • 30
  • [ 134997-74-3 ]
  • [ 917342-01-9 ]
  • 31
  • [ 134997-74-3 ]
  • [ 1334243-78-5 ]
  • 32
  • [ 7652-29-1 ]
  • copper(l) cyanide [ No CAS ]
  • [ 134997-74-3 ]
  • 33
  • [ 134997-74-3 ]
  • [ 916211-06-8 ]
  • 34
  • [ 134997-74-3 ]
  • [ 1354013-32-3 ]
  • 35
  • [ 134997-74-3 ]
  • [ 916208-72-5 ]
 

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[ 134997-74-3 ]

Amides

Chemical Structure| 134997-87-8

A409981 [134997-87-8]

3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid

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Chemical Structure| 869478-09-1

A119311 [869478-09-1]

8-Acetyl-6-(benzyloxy)-2H-benzo[b][1,4]oxazin-3(4H)-one

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Chemical Structure| 177210-33-2

A106984 [177210-33-2]

5-Hydroxy-2H-benzo[b][1,4]oxazin-3(4H)-one

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Chemical Structure| 68385-79-5

A102945 [68385-79-5]

N-(3-Amino-4-(2-methoxyethoxy)phenyl)acetamide

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Chemical Structure| 21744-83-2

A118095 [21744-83-2]

2-Methyl-2H-benzo[b][1,4]oxazin-3(4H)-one

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Nitriles

Chemical Structure| 928118-07-4

A188865 [928118-07-4]

3,4-Dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile

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Chemical Structure| 60979-25-1

A251846 [60979-25-1]

3-Amino-4-methoxybenzonitrile

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Chemical Structure| 177476-76-5

A105986 [177476-76-5]

4-Amino-3-methoxybenzonitrile

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Chemical Structure| 675126-27-9

A209287 [675126-27-9]

2-Amino-4-methoxy-5-(3-morpholinopropoxy)benzonitrile

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Chemical Structure| 204078-31-9

A114539 [204078-31-9]

3-Morpholinobenzonitrile

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Related Parent Nucleus of
[ 134997-74-3 ]

Other Aromatic Heterocycles

Chemical Structure| 928118-07-4

A188865 [928118-07-4]

3,4-Dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile

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Chemical Structure| 134997-87-8

A409981 [134997-87-8]

3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid

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Chemical Structure| 869478-09-1

A119311 [869478-09-1]

8-Acetyl-6-(benzyloxy)-2H-benzo[b][1,4]oxazin-3(4H)-one

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Chemical Structure| 177210-33-2

A106984 [177210-33-2]

5-Hydroxy-2H-benzo[b][1,4]oxazin-3(4H)-one

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Chemical Structure| 21744-83-2

A118095 [21744-83-2]

2-Methyl-2H-benzo[b][1,4]oxazin-3(4H)-one

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