[ CAS No. 20348-23-6 ]

Name: 20348-23-6|3,4-Dihydro-2H-pyrido[3,2-b]-1,4-oxazine|97%
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Product Details of [ 20348-23-6 ]

CAS No. :	20348-23-6	MDL No. :	MFCD09025907
Formula :	C₇H₈N₂O	Boiling Point :	285.7°C at 760 mmHg
Linear Structure Formula :	-	InChI Key :	-
M.W :	136.15 g/mol	Pubchem ID :	13196538
Synonyms :

Calculated chemistry of of [ 20348-23-6 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.29
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	40.86
TPSA :	34.15 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.48 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.44
Log Po/w (XLOGP3) :	0.91
Log Po/w (WLOGP) :	0.31
Log Po/w (MLOGP) :	0.28
Log Po/w (SILICOS-IT) :	1.43
Consensus Log Po/w :	0.87

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.7
Solubility :	2.71 mg/ml ; 0.0199 mol/l
Class :	Very soluble
Log S (Ali) :	-1.21
Solubility :	8.34 mg/ml ; 0.0613 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.34
Solubility :	0.627 mg/ml ; 0.0046 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.18

Safety of [ 20348-23-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 20348-23-6 ]

* 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.

Upstream synthesis route of [ 20348-23-6 ]
Downstream synthetic route of [ 20348-23-6 ]

[ 20348-23-6 ] Synthesis Path-Upstream 1~7

1
[ 20348-23-6 ]
[ 34950-82-8 ]

Yield	Reaction Conditions	Operation in experiment
69.5%	With N-Bromosuccinimide In N,N-dimethyl-formamide at 0℃; for 2 h;	To a solution of 3, 4-dihydro-2H-pyrido [3, 2-b] [1, 4] oxazine (500 mg, 3.67 mmol) in DMF (10 mL) was added NBS (719 mg, 4.04 mmol) at 0°C. The mixture was stirred at 0°C for 2 h. The mixture was quenched with sat. NaHCO₃ aq. ' and water at 0°C and stirred at 0°C for 20 min. The precipitate was collected by filtration. The solid was washed with water and dried in vacuo to give the title compound (549 mg, 2.55 mmol, 69.5percent) as brown solids. ^{. .} (3284) MS (ESI+), found 215.2 (M+H) (3285) ¹H NMR (300 MHz, CDC1₃) 5:3.50-3.58 (2H, m) , 4.18-4.26 (2H, m) , 4.82 (1H, brs), 7.10 (1H, d, J = 1.9 Hz), 7.72 (1H, d, J = 2.3 Hz)
28%	With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃; for 1 h;	(Example 5 Synthesis of Compounds I-114, I-110, and I-111) [Show Image][Show Image]Step 1 To a solution of Compound (14) (4.00 g, 29.4 mmol) in dimethylformamide (40 mL), N-bromosuccinimide (6.27 g, 35.3 mmol) was added. The solution was then stirred at room temperature for 1 hour. Aqueous saturated sodium bicarbonate (100 mL) and water (100 mL) were then thereto. The precipitated powder was filtered, and then washed with water. The filtrate was then extracted with diisopropyl ether. The organic layer was washed sequentially with water and saturated brine, then dried with anhydrous magnesium sulfate, and concentrated in vacuo to yield subject compound (15) (1.79 g, 28percent) as a pale yellow powder.¹H-NMR (DMSO-d₆) δ7.62 (1H, d, J= 2.1Hz), 7.14 (1H, d, J =2.1Hz), 6.98 (1H, br s), 4.11 (2H, t, J=4.5Hz), 3.36-3.40 (2H, m) LC/MS (Method A): 0.98 min, [M+H]⁺= 217.0.

Reference： [1] Patent: WO2018/30550, 2018, A1, . Location in patent: Paragraph 0596
[2] Patent: EP2341052, 2011, A1, . Location in patent: Page/Page column 40
[3] Acta Chemica Scandinavica (1947-1973), 1971, vol. 25, p. 3135 - 3143
[4] Patent: KR101576386, 2015, B1, . Location in patent: Paragraph 0158-0160

2
[ 20348-09-8 ]
[ 20348-23-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran for 18 h; Heating / reflux Stage #2: With sodium hydroxide; water In tetrahydrofuran at 0℃;	a) 3,4-Dihydro-2H-pyrido[3,2-_{][l,4]oxazine; To an ice-cold solution of 4H-ρyrido[3,2-][l,4]oxazin-3-one (5.00 g, 33.3 mmol) in TηF (40 mL) was added lithium aluminum hydride (66.6 mL of a 1.0 M solution in TηF, 66.6 mmol). Following the addition, the solution was heated to reflux. After 18 h, the solution was cooled to 0}0_{C and quenched the reaction with H&2}O (4 mL) followed by NaOH (4 mL, 15percent) and H₂O (10 mL). The resulting slurry was filtered over Celite and the filtrate concentrated to give the title compound (3.87 g, 85percent) as a blue-gray powder: ¹H NMR (500 MHz, OMSO-d₆) δ 7.53 (dd, J= 4.5, 1.0 Hz, IH), 6.90-6.89 (m, IH), 6.61 (br s, IH), 6.44 (dd, J= 8.0, 3.0 Hz, IH), 4.08 (t, J= 4.5 Hz, 2H), 3.39-3.36 (m, 2H); MS (ESI) m/e \\31 (M + η)\\
79%	With sodium hydroxide; LiAlH₄ In tetrahydrofuran	a) 3,4-Dihydro-2H-pyrido[3,2-b]-1,4-oxazine To a suspension of 2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one (2.0 g, 13.3 mmole) in dry THF (40 mL) was added a solution of LiAlH₄ in THF (1.0 M, 26.6 mL, 26.6 mmole) slowly at 0°C. After 1 hr the mixture was quenched with 2.0 M NaOH until a solid formed. The mixture was dried (MgSO₄), filtered, and concentrated under reduced pressure to give the title compound (1.44 g, 79percent) as a white solid which was sufficiently pure for use in the next step: MS (ES) m/e 137 (M + H)⁺.

Reference： [1] Patent: WO2007/53131, 2007, A2, . Location in patent: Page/Page column 133
[2] Patent: EP1226138, 2004, B1,
[3] Acta Chemica Scandinavica (1947-1973), 1969, vol. 23, p. 2322 - 2324
[4] Patent: US2008/305169, 2008, A1,
[5] Patent: US2007/10670, 2007, A1, . Location in patent: Page/Page column 92
[6] Patent: US2008/64871, 2008, A1, . Location in patent: Page/Page column 56

3
[ 34950-82-8 ]
[ 20348-23-6 ]

Yield	Reaction Conditions	Operation in experiment
17%	With potassium carbonate; tricyclohexylphosphine In water; toluene at 115℃; for 96 h; Inert atmosphere; Sealed tube	In an open sealed tube, a stirred mixture of 7-bromo-3,4-dihydro-2-pyrido[3,2- b][l,4]oxazoline (Maybridge, United Kingdom) (108 mg, 0.5 mmol), palladium(II) acetate (11 mg, 0.05 mmol), tricyclohexylphosphine (28 mg, 0.1 mmol), K₂C0₃ (276 mg, 2.0 mmol) and ira/i5^,-2-(trifluoromethyl)cyclopropylboronic acid MIDA ester (159 mg, 0.6 mmol) in toluene (3 mL) and H₂0 (1 mL) was de-gassed with N₂ for 15 minutes, then the reaction mixture placed under nitrogen, heated to 115 °C and stirred for 4 days. After allowing to cool, the reaction mixture was filtered through Celite and the filter cake washed with EtOAc (3 x 20 mL), H₂0 (10 mL) and EtOAc (20 mL). The aqueous and organic layers of the filtrate were partitioned and the aqueous layer extracted with EtOAc (1 x 20 mL). The combined organic extracts were dried (Na₂S0₄), filtered and the solvent removed under vacuum to leave a crude residue. The residue was purified by preparative thin-layer chromatography (4 prep TLC plates used) using EtOAc as eluent to give the product (21 mg, 17percent) as a solid.[00232] 1H NMR (CDC1₃, 300MHz): δ 7.54 (s, 1H), 6.70 (d, / = 1.6 Hz, 1H), 4.99 (br. s, 1H), 4.21 (dt, / = 4.4, 0.7 Hz, 2H), 3.53 (t, / = 4.4 Hz, 2H), 2.26-2.19 (m, 1H), 1.74-1.61 (m, 1H), 1.33-1.26 (m, 1H), 1.10-1.03 (m, 1H). ¹³C NMR (CDC1₃, 75MHz): δ 146.6, 139.8, 138.8, 128.0 (q, / = 269 Hz), 125.4, 120.7, 65.0, 40.8, 22.7 (q, / = 36.7 Hz), 17.0 (q, / = 2.8 Hz), 10.2 (q, J = 2.2 Hz). ¹⁹F NMR (CDC1₃, 282 MHz): -66.8 (d, / = 6.8 Hz), m/z = 245.09 (M+H)⁺ HRMS (EI): [M+H]⁺ calc'd for C11H11F3N2O m/z 245.0902, found 245.0909.[00233] Also obtained from the preparative thin-layer chromatography plates was recovered 7-bromo-3,4-dihydro-2-pyrido[3,2-b][l,4]oxazoline (18 mg, 17percent) and reduced starting material, 3,4-dihydro-2-pyrido[3,2-b][l,4]oxazoline (9.4 mg, 14percent). Note: the above reaction also was successfully undertaken using the alternative ligands 2- dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, or 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl.

Reference： [1] Patent: WO2012/75316, 2012, A2, . Location in patent: Page/Page column 55

4
[ 149-73-5 ]
[ 20348-23-6 ]

Reference： [1] Patent: US2015/119385, 2015, A1, . Location in patent: Paragraph 0692; 0693
[2] Patent: WO2015/59668, 2015, A1, . Location in patent: Page/Page column 106

5
[ 16867-03-1 ]
[ 20348-23-6 ]

Reference： [1] Acta Chemica Scandinavica (1947-1973), 1969, vol. 23, p. 2322 - 2324

6
[ 959992-62-2 ]
[ 20348-23-6 ]

Reference： [1] Patent: US2015/119385, 2015, A1,

7
[ 959992-62-2 ]
[ 20348-23-6 ]

Reference： [1] Patent: WO2015/59668, 2015, A1,

[ 20348-23-6 ] Synthesis Path-Downstream 1~31

1
[ 20348-23-6 ]
[ 34950-82-8 ]

Yield	Reaction Conditions	Operation in experiment
69.5%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 2h;	To a solution of 3, 4-dihydro-2H-pyrido [3, 2-b] [1, 4] oxazine (500 mg, 3.67 mmol) in DMF (10 mL) was added NBS (719 mg, 4.04 mmol) at 0C. The mixture was stirred at 0C for 2 h. The mixture was quenched with sat. NaHCO3 aq. ' and water at 0C and stirred at 0C for 20 min. The precipitate was collected by filtration. The solid was washed with water and dried in vacuo to give the title compound (549 mg, 2.55 mmol, 69.5%) as brown solids. . . (3284) MS (ESI+), found 215.2 (M+H) (3285) 1H NMR (300 MHz, CDC13) 5:3.50-3.58 (2H, m) , 4.18-4.26 (2H, m) , 4.82 (1H, brs), 7.10 (1H, d, J = 1.9 Hz), 7.72 (1H, d, J = 2.3 Hz)
28%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	(Example 5 Synthesis of Compounds I-114, I-110, and I-111) [Show Image][Show Image]Step 1 To a solution of Compound (14) (4.00 g, 29.4 mmol) in dimethylformamide (40 mL), N-bromosuccinimide (6.27 g, 35.3 mmol) was added. The solution was then stirred at room temperature for 1 hour. Aqueous saturated sodium bicarbonate (100 mL) and water (100 mL) were then thereto. The precipitated powder was filtered, and then washed with water. The filtrate was then extracted with diisopropyl ether. The organic layer was washed sequentially with water and saturated brine, then dried with anhydrous magnesium sulfate, and concentrated in vacuo to yield subject compound (15) (1.79 g, 28%) as a pale yellow powder.1H-NMR (DMSO-d6) delta7.62 (1H, d, J= 2.1Hz), 7.14 (1H, d, J =2.1Hz), 6.98 (1H, br s), 4.11 (2H, t, J=4.5Hz), 3.36-3.40 (2H, m) LC/MS (Method A): 0.98 min, [M+H]+= 217.0.
	With bromine; acetic acid; at 0℃; for 3h;	AcOH (18 mL) in Fig. 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (1.00 g, 7.35 mmol) to a stirring solution of Br2 (0.472 mL, 9.19 mmol) was added dropwise at 0 C. After stirring the mixture resulting as a result from 0 C for 3 hours, it was warmed to ambient temperature such that the mixture. After the precipitate was filtered, diluted with EtOAc (200 mL) and dried in a high vacuum state was produced F1.

Reference： [1]Patent: WO2018/30550,2018,A1 .Location in patent: Paragraph 0596
[2]Patent: EP2341052,2011,A1 .Location in patent: Page/Page column 40
[3]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3135 - 3143
[4]Patent: KR101576386,2015,B1 .Location in patent: Paragraph 0158-0160

2
[ 20348-09-8 ]
[ 20348-23-6 ]

Yield	Reaction Conditions	Operation in experiment
85%		a) 3,4-Dihydro-2H-pyrido[3,2-&][l,4]oxazine; To an ice-cold solution of 4H-rhoyrido[3,2-][l,4]oxazin-3-one (5.00 g, 33.3 mmol) in TetaF (40 mL) was added lithium aluminum hydride (66.6 mL of a 1.0 M solution in TetaF, 66.6 mmol). Following the addition, the solution was heated to reflux. After 18 h, the solution was cooled to 00C and quenched the reaction with H2O (4 mL) followed by NaOH (4 mL, 15%) and H2O (10 mL). The resulting slurry was filtered over Celite and the filtrate concentrated to give the title compound (3.87 g, 85%) as a blue-gray powder: 1H NMR (500 MHz, OMSO-d6) delta 7.53 (dd, J= 4.5, 1.0 Hz, IH), 6.90-6.89 (m, IH), 6.61 (br s, IH), 6.44 (dd, J= 8.0, 3.0 Hz, IH), 4.08 (t, J= 4.5 Hz, 2H), 3.39-3.36 (m, 2H); MS (ESI) m/e 31 (M + eta)
79%	With sodium hydroxide; LiAlH4; In tetrahydrofuran;	a) 3,4-Dihydro-2H-pyrido[3,2-b]-1,4-oxazine To a suspension of 2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one (2.0 g, 13.3 mmole) in dry THF (40 mL) was added a solution of LiAlH4 in THF (1.0 M, 26.6 mL, 26.6 mmole) slowly at 0C. After 1 hr the mixture was quenched with 2.0 M NaOH until a solid formed. The mixture was dried (MgSO4), filtered, and concentrated under reduced pressure to give the title compound (1.44 g, 79%) as a white solid which was sufficiently pure for use in the next step: MS (ES) m/e 137 (M + H)+.
	With sodium hydroxide; In tetrahydrofuran; water;	Step 1 Production of 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine Lithium aluminum hydride (2 g) was suspended in tetrahydrofuran (80 mL), and <strong>[20348-09-8]4H-pyrido[3,2-b][1,4]oxazin-3-one</strong> (3.956 g) was added under ice-cooling by small portions. After heating under reflux for 2 hrs, water (2 mL), 15% aqueous sodium hydroxide (2 mL) and water (6 mL) were successively added under ice-cooling, and the mixture was stirred at room temperature. The mixture was dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (n-hexane-ethyl acetate=1:9) to give the title compound (3.407 g) as a white solid.

		Step 1 Production of 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine Lithium aluminum hydride (2 g) was suspended in tetrahydrofuran (80 mL), and <strong>[20348-09-8]4H-pyrido[3,2-b][1,4]oxazin-3-one</strong> (3.956 g) was added under ice-cooling by small portions. After heating under reflux for 2 hrs, water (2 mL), 15% aqueous sodium hydroxide (2 mL) and water (6 mL) were successively added under ice-cooling, and the mixture was stirred at room temperature. The mixture was dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (n-hexane-ethyl acetate=1:9) to give the title compound (3.407 g) as a white solid.
		Step 1 Production of 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine Lithium aluminum hydride (2 g) was suspended in tetrahydrofuran (80 mL), and <strong>[20348-09-8]4H-pyrido[3,2-b][1,4]oxazin-3-one</strong> (3.956 g) was added under ice-cooling by small portions. After heating under reflux for 2 hrs, water (2 mL), 15% aqueous sodium hydroxide (2 mL) and water (6 mL) were successively added under ice-cooling, and the mixture was stirred at room temperature. The mixture was dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (n-hexane-ethyl acetate=1:9) to give the title compound (3.407 g) as a white solid.

Reference： [1]Patent: WO2007/53131,2007,A2 .Location in patent: Page/Page column 133
[2]Patent: EP1226138,2004,B1
[3]Acta Chemica Scandinavica (1947),1969,vol. 23,p. 2322 - 2324
[4]Patent: US2008/305169,2008,A1
[5]Patent: US2007/10670,2007,A1 .Location in patent: Page/Page column 92
[6]Patent: US2008/64871,2008,A1 .Location in patent: Page/Page column 56

3
[ 20348-23-6 ]
[ 100-39-0 ]
[ 19612-61-4 ]

Reference： [1]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3135 - 3143

4
[ 20348-23-6 ]
[ 109-54-6 ]
[ 19612-60-3 ]

Reference： [1]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3135 - 3143

5
[ 20348-23-6 ]
[ 106-95-6 ]
4-allyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine [ No CAS ]

Reference： [1]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3135 - 3143

6
[ 20348-23-6 ]
[ 107-13-1 ]
[ 34950-71-5 ]

Reference： [1]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3135 - 3143

7
[ 20348-23-6 ]
C-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-methylamine [ No CAS ]

Reference： [1]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3135 - 3143

8
[ 20348-23-6 ]
[ 34945-66-9 ]

Reference： [1]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3135 - 3143

9
[ 16867-03-1 ]
[ 20348-23-6 ]

Reference： [1]Acta Chemica Scandinavica (1947),1969,vol. 23,p. 2322 - 2324

10
[ 20348-23-6 ]
[ 354575-15-8 ]
(4-benzyloxy-3,5-dichlorophenyl)-(2,3-dihydropyrido[3,2-b][1,4]oxazin-4-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In chloroform; at 20℃; for 12h;	Step 2 Production of (4-benzyloxy-3,5-dichlorophenyl)-(2,3-dihydropyrido[3,2-b][1,4]oxazin-4-yl)-methanone 3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazine (272 mg) was dissolved in chloroform (15 mL), and triethylamine (0.335 mL) and 4-benzyloxy-3,5-dichlorobenzoyl chloride (662 mg) obtained in Step 3 of Example 8 were added under ice-cooling. The mixture was stirred at room temperature for 12 hrs, and the reaction mixture was purified by silica gel chromatography (n-hexane-ethyl acetate=4:1) to give the title compound (646 mg) as a white solid.
	With triethylamine; In chloroform; at 0 - 40℃; for 12h;	Step 2 Production of (4-benzyloxy-3,5-dichlorophenyl)-(2,3-dihydropyrido[3,2-b][1,4]oxazin-4-yl)-methanone 3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazine (272 mg) was dissolved in chloroform (15 mL), and triethylamine (0.335 mL) and 4-benzyloxy-3,5-dichlorobenzoyl chloride (662 mg) obtained in Step 3 of Example 8 were added under ice-cooling. The mixture was stirred at room temperature for 12 hrs, and the reaction mixture was purified by silica gel chromatography (n-hexane-ethyl acetate=4:1) to give the title compound (646 mg) as a white solid.

Reference： [1]Patent: US2007/10670,2007,A1 .Location in patent: Page/Page column 92
[2]Patent: US2008/64871,2008,A1 .Location in patent: Page/Page column 56

11
[ 20348-23-6 ]
7-bromo-2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine hydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With bromine; acetic acid; at 0 - 20℃; for 5h;	b) 7-Bromo-2,2-dimethyl-3,4-dihydro-2H-rhoyrido[3,2-6][l,4]oxazine hydrogen bromide; To an ice-cold solution of 3,4-dihydro-2H-pyrido[3,2-&][l,4]oxazine (3.86 g, 28.3 mmol) in acetic acid (71.7 mL) was added Br2 (1.83 mL, 35.6 mmol). The mixture was stirred for 3 h at 00C then warmed to ambient temperature. After 2 h, the resulting solids were collected by filtration and washed with EtOAc (400 mL). The solids were dried to give the title compound (6.31 g, 60%) as a dark orange powder: 1H NMR (300 MHz, DMSO-4) delta 12.25 (br s, IH), 7.77 (t; J= 1.8 Hz, IH), 7.45 (t, J= 2.1 Hz, IH), 4.20 (t, J= 4.6 Hz, 2H), 3.48 (t, J= 4.6 Hz, 2H); MS (ESl) m/e 215 (M + H)+.

Reference： [1]Patent: WO2007/53131,2007,A2 .Location in patent: Page/Page column 133

12
[ 20348-23-6 ]
[ 24424-99-5 ]
[ 335030-28-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With ammonium chloride; In tetrahydrofuran;	b) 4-(tert-Butoxycarbonyl)-3,4-dihydro-2H-pyrido[3,2-b]-1,4-oxazine To a solution of 3,4-dihydro-2H-pyrido[3,2-b]-1,4-oxazine (1.44 g, 10.6 mmole) and di-tert-butyl dicarbonate (2.78 g, 12.7 mmole) in dry THF (50 mL) was added a solution of LiHMDS in THF (1.0 M, 12.7 mL, 12.7 mmole) dropwise at 0C. After 30 min the mixture was quenched with saturated NH4Cl and extracted with EtOAc (3x). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash chromatography on silica gel (40% EtOAc/hexanes) gave the title compound (2.0 g, 80%) as a clear oil: MS (ES) m/e 237 (M + H)+.

Reference： [1]Patent: EP1226138,2004,B1

13
[ 20348-23-6 ]
[ 888730-53-8 ]
[ 354575-15-8 ]
(4-benzyloxy-3,5-dichlorophenyl)-(2,3-dihydropyrido[3,2-b][1,4]oxazin-4-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In 2-nitro-4-(pyrrolidine-1-sulfonyl)phenol; chloroform;	Step 2 Production of (4-benzyloxy-3,5-dichlorophenyl)-(2,3-dihydropyrido[3,2-b][1,4]oxazin-4-yl)-methanone 3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazine (272 mg) was dissolved in chloroform (15 mL), and triethylamine (0.335 mL) and 4-benzyloxy-3,5-dichlorobenzoyl chloride (662 mg) obtained in Step 3 of Reference Example 8 were added under ice-cooling. The mixture was stirred at room temperature for 12 hrs, and the reaction mixture was purified by silica gel chromatography (n-hexane-ethyl acetate=4:1) to give the title compound (646 mg) as a white solid.

Reference： [1]Patent: US2008/305169,2008,A1

14
[ 20348-23-6 ]
[ 252742-72-6 ]
C₁₀H₁₁N₅O₂ [ No CAS ]