[ CAS No. 72804-96-7 ] {[proInfo.proName]}

Name: 72804-96-7|O-Diphenylphosphinylhydroxylamine|98%
Brand: Ambeed
SKU: A184173
Rating: 96 (28 reviews)

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Quality Control of [ 72804-96-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 72804-96-7 ]

SDS Specification

Alternatived Products of [ 72804-96-7 ]

Product Details of [ 72804-96-7 ]

CAS No. :	72804-96-7	MDL No. :	MFCD12755701
Formula :	C₁₂H₁₂NO₂P	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SJECIYLGISUNRO-UHFFFAOYSA-N
M.W :	233.20	Pubchem ID :	10955453
Synonyms :

Calculated chemistry of [ 72804-96-7 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.0
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	64.61
TPSA :	62.13 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.44 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.78
Log Po/w (XLOGP3) :	1.8
Log Po/w (WLOGP) :	1.81
Log Po/w (MLOGP) :	2.54
Log Po/w (SILICOS-IT) :	1.33
Consensus Log Po/w :	1.85

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.78
Solubility :	0.39 mg/ml ; 0.00167 mol/l
Class :	Soluble
Log S (Ali) :	-2.72
Solubility :	0.44 mg/ml ; 0.00189 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.32
Solubility :	0.0111 mg/ml ; 0.0000478 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.98

Safety of [ 72804-96-7 ]

Signal Word:	Danger	Class:	4.1
Precautionary Statements:	P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313	UN#:	1325
Hazard Statements:	H228-H315-H319	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 72804-96-7 ]

* 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 [ 72804-96-7 ]
Downstream synthetic route of [ 72804-96-7 ]

[ 72804-96-7 ] Synthesis Path-Upstream 1~5

1
[ 1499-21-4 ]
[ 72804-96-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium hydroxide; hydroxylamine hydrochloride In 1,4-dioxane; water at 0 - 22℃; for 0.166667 h;	A 5 L 4-neck round bottom flask (rbf) fitted with an overhead stirrer a thermocouple was charged with; (1) a solution of NaOH (60.85 g, 1.52 mol, 2.4 eq) in 180 mL water, (2) a solution of hydroxylamine-HCl (110.12 g, 1.58 mol, 2.5 eq) in 180 mL water and (3) 180 mL dioxane. The mixture was cooled in an ice/acetone bath to to 0 °C. 150 g of ice was added, followed by a precooled (to about 10 °C) solution of diphenylphosphinic chloride (150.0 g, 0.634 mol, 1 eq) in 180 mL dioxane (added all at once). The reaction became very thick with a white precipitate, requiring vigorous stirring. The internal temperature rose to 22 0C. After 5 additional minutes stirring (10 minutes maximum) , the reaction mixture was diluted with 2.5 L of ice cold water and filterered thru a large fritted funnel (15 cm diameter). The crude material was left on the frit to drain for one hour, then transfered back into the 5 L rbf. The solid was suspended in 500 mL ice cold 0.25N NaOH solution and vigorously stirred for five minutes (no more than 10 min), then filterered again, washing 2x with ice cold water and left to dry overnight on the fritted filter. The partially dried material was dried for 12 h in a vacuum oven (50 °C, 0.1 torr) and then well crushed with a mortar pestal. An additional 16 h of drying in the vacuum oven afforded 122 g (82 percent) the above compound as a white powder.
75%	With hydroxylamine hydrochloride; triethylamine In dichloromethane at -20 - 20℃;	Using a variation of the Knoevenagel procedure described for the preparation of 50, ethyl 2-pyridylacetate (500 mg, 3.02 mmol) was dissolved in anhydrous THF (8 mL) and the solution cooled to -78° C. under a nitrogen atmosphere. Lithium bis(trimethylsilyl)amide (1M in THF, 3.00 mL, 3.00 mmol) was added via syringe over 10 min followed by 3-furaldehyde (290 mg, 3.02 mmol) and the yellow solution allowed to warm to -40° C., with further stirring at this temperature for 2 h. Acetic anhydride (616 mg, 6.04 mmol) was added and the reaction allowed to warm to rt. Triethylamine (610 mg, 6.04 mmol) was added and the solution stirred overnight at rt and then at 55° C. for 3 h or until elimination was complete (as determined by LCMS). The solvent was evaporated and the brown solid chromatographed on silica (eluent 30percent EtOAc in DCM) to afford the title compound as mixture of regioisomers which were separately isolated during the chromatography step; combined yield 540 mg, 73percent); MS m/e 244 (MH)⁺.
61%	With hydroxylamine hydrochloride; sodium hydroxide In 1,4-dioxane; water at -5℃; for 0.25 h;	To a solution of hydroxylamine hydrochloride (7.3 g, 106 mmol, 2.5 eq) in water (12 mL) and dioxane (12 mL) was added a solution of NaOH (4.07 g, 102 mmol, 2.4 eq) in water (12 mL), and the mixture was cooled to −5° C. in an ice/salt bath. A solution of diphenylphosphinic chloride (10 g, 42 mmol, 1 eq) in dioxane (12 mL), precooled to below 10° C., was rapidly added to the above solution in an ice/salt bath under vigorous stirring. After completion of the addition, the mixture was stirred for additional 5 minutes in an ice/salt bath, then diluted with ice water (150 mL) and filtered. The filtration cake was washed with ice water, and lyophilized to give o-(diphenylphosphoryl)hydroxylamine (6.0 g, yield 61percent) as a white solid. MS (ES+) requires: 233. found 234 [M+H]⁺; purity: 75percent.

59%	With hydroxylamine hydrochloride; sodium hydroxide In 1,4-dioxane; water for 0.0833333 h; Cooling with ice-salt bath	Example 17A O-(diphenylphosphoryl)hydroxylamineTo a stirred solution of hydroxylamine hydrochloride (9.5 g, 137 mmol) in H₂O (21 mL) was added aqueous sodium hydroxide (4.6 g, 116 mmol) in H₂O (16 mL), followed by dioxane (66 mL). The resulting solution was cooled in an ice/salt bath, and diphenylphosphinyl chloride (11.8 g, 50 mmol) in dioxane (50 mL) was added in one portion with vigorous stirring. Stirring was continued for 5 minutes as copious precipitation ensued. Water (200 mL) was added, and the slurry filtered, and was purified by stirring the slurry with aqueous sodium hydroxide (1 g, 25 mmol) in water (100 mL) at 0° C. for 30 min, followed by filtration and drying in vacuo to afford 6.8 g (59percent) of the title compound. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 7.38-7.57 (m, 6H) 7.64-7.79 (m, 4H).
56%	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 30℃; for 2 h; Inert atmosphere	To a suspension of hydroxylamine hydrochloride (735 g, ‘LOS mol) in dichloromethane (500 mL) was added DIPEA (136 g, t05 mol) over 15 minutes at 30 C under a nitrogen atmosphere. A white precipitate formed upon the addition. After stirring for one hour at that temperature, a solution of diphenylphosphinic chloride A (50 g, 02 mol) in dichloromethane (100 mL) was added over 60 minutes,The mixture reaction was warmed to 0 °C over 1 hour with stirring. The reaction was quenched by adding water (200 mL) over 10 minutes. After stirring the mixture for 05 hour, the precipitate was coHected by filtration and washed with water (100 mL x 2). Then the solid was dried under reduced pressure to afford a crude product. The crude product was triturated in EtOH to afford compound B (27 g, 56percent yield) as a whitesolid,1HNMR (400 MHz, CD3OD): 677,91479 (rn, SF1), 7,62-7.50 (m, 7H). MS Calcd,: 233; MS Found: 234 ([M+Hj4’).
36%	Stage #1: With sodium hydroxide; hydroxylamine hydrochloride In 1,4-dioxane; water at 0℃; for 0.25 h; Stage #2: at 0℃; for 0.25 h; Stage #3: With sodium hydroxide In water at 0℃; for 1 h;	To hydroxylamine hydrochloride (15.86 g, 228.2 mmol) in H20 (35 mL) cooled in an ice-salt bath was added 7.1 N NaOH (27.4 mL, 194.4 mmol) followed by 1,4-dioxane (100 mL). The solution was vigorously stirred for 15 min and then chlorodiphenylphosphine oxide (20.00 g, 84.52 mmol) was added as a solution in 1,4-dioxane (100 mL). The solution was stirred an additional 15 min as a white precipitate formed which was filtered. The solid was suspended in 0.25 N NaOH (250mL) while stirring in an ice-salt bath for 1 h. The solid was then collected, washed with H20 (100 mL), and thoroughly dried under vacuum to afford 7.09 g of the above compound as a white powder (30.4 mmol, yield 36percent). (at)H-NMR (DMSO- d6) No. 7.72 to 7.67 (m, 4H), 7.50 to 7.40 (m, 6H) ; ³¹P-NMR (DMSO-d6) (at) 23.11 (br s, IP).

Reference： [1] Patent: WO2007/64883, 2007, A2, . Location in patent: Page/Page column 190
[2] Organic Preparations and Procedures International, 2011, vol. 43, # 5, p. 475 - 476
[3] Patent: US2009/257979, 2009, A1, . Location in patent: Page/Page column 91-92
[4] Synthesis, 1982, # 7, p. 592 - 595
[5] Organic Letters, 2005, vol. 7, # 13, p. 2767 - 2770
[6] Journal of Organic Chemistry, 1998, vol. 63, # 4, p. 1221 - 1225
[7] Organic Letters, 2007, vol. 9, # 2, p. 351 - 353
[8] Patent: US2015/111887, 2015, A1, . Location in patent: Paragraph 0177; 0178
[9] Patent: US2011/124642, 2011, A1, . Location in patent: Page/Page column 24
[10] Patent: WO2017/5786, 2017, A1, . Location in patent: Page/Page column 57
[11] Tetrahedron, 2009, vol. 65, # 29-30, p. 5805 - 5816
[12] Patent: WO2005/121147, 2005, A1, . Location in patent: Page/Page column 68; 69
[13] Tetrahedron Letters, 1982, vol. 23, # 37, p. 3835 - 3836
[14] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 3284 - 3288
[15] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 5, p. 582 - 586
[16] Patent: WO2004/63197, 2004, A1, . Location in patent: Page 81
[17] Patent: US2009/258883, 2009, A1, . Location in patent: Page/Page column 6
[18] Patent: US2009/298813, 2009, A1,
[19] Patent: WO2015/95767, 2015, A1, . Location in patent: Page/Page column 149; 150
[20] Patent: US2016/31892, 2016, A1, . Location in patent: Paragraph 0083-0084

2
[ 2524-64-3 ]
[ 72804-96-7 ]

Yield	Reaction Conditions	Operation in experiment
36%	With sodium hydroxide; hydroxylamine hydrochloride In 1,4-dioxane; water at 0℃; for 0.5 h;	To hydroxylamine hydrochloride (15.86 g, 228.2 mmol) in water (35 mL) cooled in an ice- salt bath was added 7.1 N aqueous sodium hydroxide (27.4 mL, 194.4 mmol) followed by 1 ,4-dioxane (100 mL). The solution was vigorously stirred for 15 min and then chlorodiphenylphosphine oxide (20.00 g, 84.52 mmol) was added as a solution in 1,4- dioxane (100 mL). The solution was stirred an additional 15 min as a white precipitate formed. The precipitate was collected and then suspended in cold (0 °) 0.25 N aqueous sodium hydroxide (250 mL). The mixture was stirred for 1 h and then the solid was collected, washed with water (100 mL), and thoroughly dried under vacuum to afford the desired intermediate (7.09 g, 36percent) as a white solid. ¹H-NMR (300 MHz, DMSO-cfe) .sect. 7.65- 7.74 (m, 4 H), 7.38-7.42 (m, 6 H); ³¹P-NMR (DMSOd₆) ξ 23.11 (br s, 1 P).

Reference： [1] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3499 - 3502
[2] Patent: WO2007/64932, 2007, A2, . Location in patent: Page/Page column 46-47

3
[ 5470-11-1 ]
[ 1499-21-4 ]
[ 72804-96-7 ]

Reference： [1] Patent: WO2014/8197, 2014, A1, . Location in patent: Page/Page column 134; 135

4
[ 73452-52-5 ]
[ 72804-96-7 ]

Reference： [1] Tetrahedron Letters, 1983, vol. 24, # 30, p. 3115 - 3116

5
[ 73452-52-5 ]
[ 124-41-4 ]
[ 72804-96-7 ]
[ 18357-17-0 ]
[ 1706-90-7 ]

Reference： [1] Tetrahedron Letters, 1983, vol. 24, # 30, p. 3115 - 3116

[ 72804-96-7 ] Synthesis Path-Downstream 1~44

1
[ 75-18-3 ]
[ 72804-96-7 ]
aminodimethylsulphonium diphenylphosphinate [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1981,p. 3284 - 3288

2
[ 73452-52-5 ]
[ 124-41-4 ]
[ 72804-96-7 ]
[ 18357-17-0 ]
[ 1706-90-7 ]

Reference： [1]Tetrahedron Letters,1983,vol. 24,p. 3115 - 3116

3
[ 73452-52-5 ]
[ 72804-96-7 ]

Reference： [1]Tetrahedron Letters,1983,vol. 24,p. 3115 - 3116

4
[ 72804-96-7 ]
[ 108-24-7 ]
[ 72804-97-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1981,p. 3284 - 3288

5
[ 72804-96-7 ]
[ 603-35-0 ]
aminotriphenylphosphonium diphenylphosphinate [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1981,p. 3284 - 3288

6
[ 72804-96-7 ]
[ 67-64-1 ]
[ 72804-98-9 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1981,p. 3284 - 3288

7
[ 1499-21-4 ]
[ 72804-96-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium hydroxide; hydroxylamine hydrochloride; In 1,4-dioxane; water; at 0 - 22℃; for 0.166667h;	A 5 L 4-neck round bottom flask (rbf) fitted with an overhead stirrer & a thermocouple was charged with; (1) a solution of NaOH (60.85 g, 1.52 mol, 2.4 eq) in 180 mL water, (2) a solution of hydroxylamine-HCl (110.12 g, 1.58 mol, 2.5 eq) in 180 mL water and (3) 180 mL dioxane. The mixture was cooled in an ice/acetone bath to to 0 C. 150 g of ice was added, followed by a precooled (to about 10 C) solution of diphenylphosphinic chloride (150.0 g, 0.634 mol, 1 eq) in 180 mL dioxane (added all at once). The reaction became very thick with a white precipitate, requiring vigorous stirring. The internal temperature rose to 22 0C. After 5 additional minutes stirring (10 minutes maximum) , the reaction mixture was diluted with 2.5 L of ice cold water and filterered thru a large fritted funnel (15 cm diameter). The crude material was left on the frit to drain for one hour, then transfered back into the 5 L rbf. The solid was suspended in 500 mL ice cold 0.25N NaOH solution and vigorously stirred for five minutes (no more than 10 min), then filterered again, washing 2x with ice cold water and left to dry overnight on the fritted filter. The partially dried material was dried for 12 h in a vacuum oven (50 C, 0.1 torr) and then well crushed with a mortar & pestal. An additional 16 h of drying in the vacuum oven afforded 122 g (82 %) the above compound as a white powder.
75%	With hydroxylamine hydrochloride; triethylamine; In dichloromethane; at -20 - 20℃;	Using a variation of the Knoevenagel procedure described for the preparation of 50, ethyl 2-pyridylacetate (500 mg, 3.02 mmol) was dissolved in anhydrous THF (8 mL) and the solution cooled to -78 C. under a nitrogen atmosphere. Lithium bis(trimethylsilyl)amide (1M in THF, 3.00 mL, 3.00 mmol) was added via syringe over 10 min followed by 3-furaldehyde (290 mg, 3.02 mmol) and the yellow solution allowed to warm to -40 C., with further stirring at this temperature for 2 h. Acetic anhydride (616 mg, 6.04 mmol) was added and the reaction allowed to warm to rt. Triethylamine (610 mg, 6.04 mmol) was added and the solution stirred overnight at rt and then at 55 C. for 3 h or until elimination was complete (as determined by LCMS). The solvent was evaporated and the brown solid chromatographed on silica (eluent 30% EtOAc in DCM) to afford the title compound as mixture of regioisomers which were separately isolated during the chromatography step; combined yield 540 mg, 73%); MS m/e 244 (MH)+.
61%	With hydroxylamine hydrochloride; sodium hydroxide; In 1,4-dioxane; water; at -5℃; for 0.25h;	To a solution of hydroxylamine hydrochloride (7.3 g, 106 mmol, 2.5 eq) in water (12 mL) and dioxane (12 mL) was added a solution of NaOH (4.07 g, 102 mmol, 2.4 eq) in water (12 mL), and the mixture was cooled to -5 C. in an ice/salt bath. A solution of diphenylphosphinic chloride (10 g, 42 mmol, 1 eq) in dioxane (12 mL), precooled to below 10 C., was rapidly added to the above solution in an ice/salt bath under vigorous stirring. After completion of the addition, the mixture was stirred for additional 5 minutes in an ice/salt bath, then diluted with ice water (150 mL) and filtered. The filtration cake was washed with ice water, and lyophilized to give o-(diphenylphosphoryl)hydroxylamine (6.0 g, yield 61%) as a white solid. MS (ES+) requires: 233. found 234 [M+H]+; purity: 75%.

59%	With hydroxylamine hydrochloride; sodium hydroxide; In 1,4-dioxane; water; for 0.0833333h;Cooling with ice-salt bath;	Example 17A O-(diphenylphosphoryl)hydroxylamineTo a stirred solution of hydroxylamine hydrochloride (9.5 g, 137 mmol) in H2O (21 mL) was added aqueous sodium hydroxide (4.6 g, 116 mmol) in H2O (16 mL), followed by dioxane (66 mL). The resulting solution was cooled in an ice/salt bath, and diphenylphosphinyl chloride (11.8 g, 50 mmol) in dioxane (50 mL) was added in one portion with vigorous stirring. Stirring was continued for 5 minutes as copious precipitation ensued. Water (200 mL) was added, and the slurry filtered, and was purified by stirring the slurry with aqueous sodium hydroxide (1 g, 25 mmol) in water (100 mL) at 0 C. for 30 min, followed by filtration and drying in vacuo to afford 6.8 g (59%) of the title compound. 1H NMR (300 MHz, DMSO-d6) delta ppm 7.38-7.57 (m, 6H) 7.64-7.79 (m, 4H).
56%	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 30℃; for 2h;Inert atmosphere;	To a suspension of hydroxylamine hydrochloride (735 g, ?LOS mol) in dichloromethane (500 mL) was added DIPEA (136 g, t05 mol) over 15 minutes at 30 C under a nitrogen atmosphere. A white precipitate formed upon the addition. After stirring for one hour at that temperature, a solution of diphenylphosphinic chloride A (50 g, 02 mol) in dichloromethane (100 mL) was added over 60 minutes,The mixture reaction was warmed to 0 C over 1 hour with stirring. The reaction was quenched by adding water (200 mL) over 10 minutes. After stirring the mixture for 05 hour, the precipitate was coHected by filtration and washed with water (100 mL x 2). Then the solid was dried under reduced pressure to afford a crude product. The crude product was triturated in EtOH to afford compound B (27 g, 56% yield) as a whitesolid,1HNMR (400 MHz, CD3OD): 677,91479 (rn, SF1), 7,62-7.50 (m, 7H). MS Calcd,: 233; MS Found: 234 ([M+Hj4?).
56%	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 30℃; for 2h;Inert atmosphere;	To a suspension of hydroxy lamine hydrochloride (73.5 g, 1.05 mol) in dichloromethane (500 mL) was added DIPEA (136 g, 1.05 mol) over 15 minutes at - 30 C under a nitrogen atmosphere. A white precipitate formed upon the addition. After stirring for one hour at that temperature, a solution of diphenylphosphinic chloride A (50 g, 0.2 mol) in dichloromethane (100 mL) was added over 60 minutes. The mixture reaction was warmed to 0 C over 1 hour with stirring. The reaction was quenched by adding water (200 mL) over 10 minutes. After stirring the mixture for 0.5 hour, the precipitate was collected by filtration and washed with water (100 mL x 2). Then the solid was dried under reduced pressure to afford a crude product. The crude product was triturated in EtOH to afford compound B (27 g, 56% yield) as a white solid. TTNMR (400 MHz, CD30D): 577.91-7.79 (m, 5H), 7.62-7.50 (m, 7H). MS Calcd.: 233; MS Found: 234 ([M+H]+).
36%		To hydroxylamine hydrochloride (15.86 g, 228.2 mmol) in H20 (35 mL) cooled in an ice-salt bath was added 7.1 N NaOH (27.4 mL, 194.4 mmol) followed by 1,4-dioxane (100 mL). The solution was vigorously stirred for 15 min and then chlorodiphenylphosphine oxide (20.00 g, 84.52 mmol) was added as a solution in 1,4-dioxane (100 mL). The solution was stirred an additional 15 min as a white precipitate formed which was filtered. The solid was suspended in 0.25 N NaOH (250mL) while stirring in an ice-salt bath for 1 h. The solid was then collected, washed with H20 (100 mL), and thoroughly dried under vacuum to afford 7.09 g of the above compound as a white powder (30.4 mmol, yield 36%). (at)H-NMR (DMSO- d6) No. 7.72 to 7.67 (m, 4H), 7.50 to 7.40 (m, 6H) ; 3¹P-NMR (DMSO-d6) (at) 23.11 (br s, IP).
		To a suspension of hydroxylamine hydrochloride (29.4 g) in dichloromethane (200 mL) was added diisopropylethylamine (54.6 g) over 3 minutes in a methanol-ice bath under a nitrogen atmosphere. A white precipitate was formed upon the addition. After stirring for 1 hour under the bath, a solution of diphenylphosphinic chloride (20.0 g) in dichloromethane (20 mL) was added over 60 minutes. A white crystal was formed upon the addition. The mixture was warmed to0 C over 1 hour with stirring. The reaction was quenched by adding water (200 mL) over 3 minutes. After stirring the mixture for 0.5 hour, the crystal was collected by filtration. The crystal was washed with water (50 * 3 mL) followed by diisopropyl ether (50 * 3 mL). The collected crystal was dried overnight in the air and 3 hours under a reduced pressure with slight warming (4 C) to give a crude product. The crude product was triturated in EtOH (ethanol) to give (aminooxy) (diphenyl) phosphine oxide as a white crystal (15.3 g). (Aminooxy) (diphenyl) phosphine oxide NMR(CDCl3,delta) : 7.54-7. 58 (6H, m), 7.74-7. 83 (4H, m), 8.20-8. 33 (2H, m)
	With sodium hydroxide; hydroxylamine hydrochloride; In 1,4-dioxane; water; at -15℃; for 0.333333h;	Preparation 1 O-diphenylphosphinylhydroxylamine To an aqueous solution of 149.44 g of hydroxylamine hydrochloride (340 ml of water) there are added a solution of 72.75 g of sodium hydroxide (290 ml of water) and 960 ml of 1,4-dioxane. The mixture is cooled to -15 C. and then, after 15 minutes, a solution of 180 g of diphenylphosphinyl chloride in 725 ml of dioxane is added all at once with mechanical stirring. After 5 minutes, 3 litres of water are added all at once. A white precipitate forms which is filtered off and then taken up in 0.25M sodium hydroxide solution at 0 C. The mixture is mechanically stirred at 0 C. for 30 minutes before being filtered again. The precipitate is dried in vacuo (phosphorus pentoxide) to yield 72.5 g of the expected product. Melting point: 104 C. Elemental microanalyses: C % H % N % Calculated: 61.80 5.19 6.01 Found: 61.20 5.07 5.72
	With hydroxylamine hydrochloride; In 1,4-dioxane; sodium hydroxide; water;	PREPARATION 1 O-diphenylphosphinylhydroxylamine To an aqueous solution of 149.44 g of hydroxylamine hydrochloride (340 ml of water) there are added a solution of 72.75 g of sodium hydroxide (290 ml of water-) and 960 ml of 1,4-dioxane. The mixture is cooled to -15 C. and then, after 15 minutes, a solution of 180 g of diphenylphosphinyl chloride in 725 ml of dioxane is added all at once with mechanical stirring. After 5 minutes, 3 litres of water are added all at once. A white precipitate forms which is filtered off and then taken up in 0.25M sodium hydroxide solution at 0 C. The mixture is mechanically stirred at 0 C. for 30 minutes before being filtered again. The precipitate is dried in vacuo (phosphorus pentoxide) to yield 72.5 g of the expected product. Melting point: 104 C. Elemental microanalyses:
	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In 1,4-dioxane; water; at 0 - 20℃; for 2.5h;	Compound 64.1. (Aminooxy)diphenylphosphine oxide. Into a 500-mL three neck round-bottom flask, was placed a solution of hydroxylamine hydrochloride (30.0 g, 432 mmol) in H20/dioxane (90/45 mL). The solution was cooled to 0-5 C, then sodium bicarbonate (36.5 g, 434 mmol) was added portion-wise over 10 min and the mixture was stirred at 0-5 C for 30 min. A solution of diphenylphosphinoyl chloride (41.0 g, 173 mmol) in dioxane (45 mL) was added drop-wise at 0-5C over 30 min, then the resulting mixture was stirred for an additional 2 h at ambient temperature. The resulting solids were collected by filtration and washed with water (200 mL), NaOH (0.25 M, 200 mL) and PE (200 mL). The product was dried to yield the title compound as a white solid (20 g, crude).
	With hydroxylamine hydrochloride; sodium hydroxide; In 1,4-dioxane; water; at 0 - 10℃;	[0084] To a solution of hydroxylamine hydrochloride (7.3g, 106 mmol, 2.5 eq) in water (12 mL) and dioxane (12 mL)was added a solution ofNaOH (4.07 g, 102 mmol, 2.4 eq) inwater (12 mL), and the mixture was cooled to -5 C. in anice/salt bath. A solution of diphenylphosphinic chloride (1 0 g,42 mmol, 1 eq) in dioxane (12 mL), precooled to below 10C., was rapidly added to the above solution in an ice/salt bathunder vigorous stirring. After completion of the addition, themixture was stirred for additional 5 minutes in an ice/saltbath, then diluted with ice water (150 mL) and filtered. Thefiltration cake was washed with ice water, and lyophilized togive o-(diphenylphosphoryl)hydroxylamine (6.0 g, yield61%) as a white solid. MS (ES+) requires: 233. found 234[M+Hr; purity: 75%.

Reference： [1]Patent: WO2007/64883,2007,A2 .Location in patent: Page/Page column 190
[2]Organic Preparations and Procedures International,2011,vol. 43,p. 475 - 476
[3]Patent: US2009/257979,2009,A1 .Location in patent: Page/Page column 91-92
[4]Synthesis,1982,p. 592 - 595
[5]Organic Letters,2005,vol. 7,p. 2767 - 2770
[6]Journal of Organic Chemistry,1998,vol. 63,p. 1221 - 1225
[7]Organic Letters,2007,vol. 9,p. 351 - 353
[8]Patent: US2015/111887,2015,A1 .Location in patent: Paragraph 0177; 0178
[9]Patent: US2011/124642,2011,A1 .Location in patent: Page/Page column 24
[10]Patent: WO2017/5786,2017,A1 .Location in patent: Page/Page column 57
[11]Patent: WO2018/9424,2018,A1 .Location in patent: Paragraph 00195; 00286-00288
[12]Tetrahedron,2009,vol. 65,p. 5805 - 5816
[13]Patent: WO2005/121147,2005,A1 .Location in patent: Page/Page column 68; 69
[14]Tetrahedron Letters,1982,vol. 23,p. 3835 - 3836
[15]Journal of the Chemical Society. Perkin transactions I,1981,p. 3284 - 3288
[16]Zeitschrift fur Naturforschung, B: Chemical Sciences,1989,vol. 44,p. 582 - 586
[17]Patent: WO2004/63197,2004,A1 .Location in patent: Page 81
[18]Patent: US2009/258883,2009,A1 .Location in patent: Page/Page column 6
[19]Patent: US2009/298813,2009,A1
[20]Patent: WO2015/95767,2015,A1 .Location in patent: Page/Page column 149; 150
[21]Patent: US2016/31892,2016,A1 .Location in patent: Paragraph 0083-0084

Yield	Reaction Conditions	Operation in experiment
		PREPARATION 2 N-aminoindole To a suspension of 177.72 g of ground potassium hydroxide in 1.3 litres of DMF there are added 21.85 g of indole and then, all at once, 72.5 g of a suspension of the compound of Preparation 1 in 1.3 litres of DMF. The thick mixture is heated at between 60 and 70 C. for 3 hours 30 minutes with mechanical stirring and then, whilst hot, is poured into 3.5 litres of ice-cold water.

9
[ 72804-96-7 ]
1-(1-amino-1H-pyrrol-2-yl)-ethanone hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of1-(lH-pyrrol-2-yl) ethanone (5.00 g) in tetrahydrofuran (100 mL) was added potassium tert-butoxide (6.17 g) in a water bath under a nitrogen atmosphere. After stirring for 1 hour, (aminooxy) (diphenyl) phosphine oxide (12.8 g) was added over 2 hours. After stirring for 2 hours at room temperature, water (4 mL) was added over 3 minutes to give a clear solution. The solvent was evaporated off, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (25 * 5 mL), and the combined organic extract was washed with brine, dried over anhydrous magnesium sulfate, and evaporated to give a brown oil (6.01 g). The oil was dissolved in diisopropyl ether (30 mL), and to the solution was added hexane (15 mL) to afford a pale yellow crystal. After stirring for 1 hour, the crystal was removed by filtration. The filtrate was evaporated to give a brown oil (5.69 g). The oil was dissolved in ethyl acetate (45.5 mL), the solution was cooled under an ice-bath. To the cooled solution was added 4N hydrogen chloride in ethyl acetate (11.5 mL) over 15 minutes to afford a pale brown precipitate. After stirring the mixture for 0.5 hour under the bath, the precipitate was collected by filtration and washed with ethyl acetate (5 * 3 mL) to give a pale brown powder (5.33 g). The powder was suspended in ethyl acetate (37 mL) and warmed to3 C. The suspension was stirred for 1 hour at room temperature. The powder was collected by filtration and washed with ethyl acetate (5 * 3 mL) to givei(1-amino-lH-pyrrol-2-yl) ethanone hydrochloride as a pale brown powder (5.25 g).1- (1-Amino-1H-pyrrol-2-yl) ethanone hydrochloride NMR (CDC13, delta) : 2.37 (3H, s), 5.22 (2H, s, br), 6.07 (1H, m), 6.99 (1H, m), 7.15 (1H, m)

Reference： [1]Patent: WO2004/63197,2004,A1 .Location in patent: Page 81-82

10
[ 862205-39-8 ]
[ 72804-96-7 ]
[ 862205-37-6 ]

Yield	Reaction Conditions	Operation in experiment
60%	With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 18h;	(f) (1-Amino-4-methyl-2-oxo-1, 2-dihvdropvridin-3-yl) acetic acid methyl ester; Caesium carbonate (1.6 g, 11.6 mmol) and 0- (diphenylphosphinyl)- hydroxylamine (1.54 g, 6.62 mmol ; see Synthesis 592 (1988) and Tetrahedron Lett. 23, 3835 (1982) ) were added to a solution of (4-Methyl- 2-oxo-l, 2-dihydropyridin-3-yl) acetic acid methyl ester (0.60 g, 3.31 mmol ; see step (e) above) in DMF (10 mL). The suspension was stirred at room temperature for 18 hours, filtered and the solvent was evaporated under reduced pressure. Purification by flash chromatography (3% methanol in ethyl acetate) gave the title compound (380 mg, 60%) as a yellow oil. 1H NMR (400 MHz, CD30D) 5 2.09 (s, 3H), 3.57 (s, 2H), 3.61 (s, 3EI), 5. 05 (br d, 2H), 5.96 (d, 1H), 7.37 (d, 1H)

Reference： [1]Patent: WO2005/75424,2005,A1 .Location in patent: Page/Page column 100

11
[ 385808-49-1 ]
[ 72804-96-7 ]
[ 385808-50-4 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; water;	B. 3-[[1-[3-(Trifluoromethyl)phenyl]hydrazino]carbonyl]-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl ester (18B) Compound 18A (308 mg, 0.8 mmol, 1 eq) was dissolved in 15 mL of tetrahydrofuran. Sodium hydride (60% in oil, 38 mg, 0.96 mmol, 1.2 eq) was added, and the mixture was stirred at rt for 15 min. O-Diphenylphosphinylhydroxylamine (224 mg, 0.96 mmol, 1.2 eq) was then added, and the reaction was stirred at rt for 1 h. LC analysis indicated that the starting material had been consumed. Water was added, and the reaction was extracted with CH2Cl2. The combined organic extracts were dried and concentrated in vacuo to provide Compound 18B as a semi-solid in quantitative yield. The compound was used without further purification. LC: R.T.=3.39 min (retention time) (YMC Combiscreen ODS-A S5 column eluding with 10-90% aqueous methanol over a 4 minute gradient.)

Reference： [1]Patent: US2003/114420,2003,A1

12
[ 132926-61-5 ]
[ 72804-96-7 ]
[ 147765-36-4 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide;	EXAMPLE 2 Methyl 2-[[-1-[4-(trifluoromethyl)phenyl]hydrazino]carbonyl]-2,3-dihydro-7-(trifluoromethyl)[1]benzopyrano[4,3-c]pyrazole-3a (4H)-carboxylate To a mixture of 60% sodium hydride (0.16 g, 4 mmol) in 10 mL of dimethylformamide was added methyl 2,3-dihydro-7-(trifluoromethyl)2-[[[4-(trifluoromethyl)phenyl]amino]carbonyl]-[1]benzopyrano[4,3-c]pyrazole-3a(4H)]-carboxylate (1.0 g, 2.05 mmol) at 0 C. in one portion. The color of the reaction turned yellow and the evolution of hydrogen gas was noted. The reaction was warmed to ambient temperature over 30 minutes, then O-diphenylphosphinylhydroxylamine (0.75 g, 3.20 mmol) was added in one portion resulting in a white suspension. An extra 10 ml portion of dimethylformamide was added and the reaction was stirred for one hour. After this time the mixture was partitioned between saturated aqueous sodium bicarbonate and ether, the aqueous phase was extracted with ether. The combined ether extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was purified by chromatography on silica gel (40% ethyl acetate/hexane) to afford an oily product. Trituration with ether and hexanes afforded 0.37 g of a white solid, m.p. 118-121 C. 1 H NMR (CDCl3) delta7.64-7.50 (m, 5H), 7.22-7.19 (m, 2H), 5.2 (bs, 2H), 5.05 (d, 1H), 4.35 (d, 1H), 4.18 (d, 1H), 3.95 (d, 1H), 3.79 (s, 3H).

Reference： [1]Patent: US5500438,1996,A

13
6-methyl-4-((3-trifluoromethyl)phenyl-3-pyridazinamine [ No CAS ]
[ 72804-96-7 ]
[ 128485-04-1 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; chloroform; water; trifluoroacetic anhydride;	EXAMPLE 14 Preparation of 6-methyl-2-(trifluoromethyl)-8-((3-trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-b]pyridazine To a slurry of 3.05 9 (13 mmol) of O-diphenylphosphinylhydroxylamine in 65 ml of chloroform was added 3.0 g (12 mmol) of 6-methyl-4-((3-trifluoromethyl)phenyl-3-pyridazinamine. The mixture was stirred for 4 hours at room temperature, was refluxed for 2 hours and then was stirred at room temperature for 16 hours. The solvent was removed with a rotary evaporator. A 100 ml portion of water was added to the residue. The pH was adjusted to 2 with 50% HI. The reaction mixture was filtered and the water was removed from the filtrate with a rotary evaporator to give 2.5 g of solid. A 1.4 g portion of this solid was placed in a teflon-capped test tube and 5 ml of trifluoroacetic anhydride was added. The test tube was placed in an oil bath heated to 200 C. for 15 minutes. After cooling, the residue was dissolved in dichloromethane and was washed with a saturated aqueous sodium bicarbonate solution and was dried (sodium sulfate). The solvent was removed with a rotary evaporator. The residue was purified by silica gel column chromatography to give 0.74 g of the title compound as a solid, m.p. 134-135.5 C.

Reference： [1]Patent: US5127936,1992,A

14
[ 72804-96-7 ]
[ 100-10-7 ]
2-(3,4-dimethoxyphenyl)-1H-imidazole [ No CAS ]
1-[[p-(dimethylamino)benzylidene]amino]-2-(3,4-dimethoxyphenyl)imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In 1-methyl-pyrrolidin-2-one; water; acetic acid;	(d) 0.45 g of sodium hydride (55 percent dispersion in oil) is washed with absolute tetrahydrofuran. A solution of 1.02 g of 2-(3,4-dimethoxyphenyl)imidazole in 50 ml of N-methylpyrrolidone is then added dropwise thereto. The mixture is stirred at room temperature for 20 minutes. 2.33 g of O-diphenylphosphinylhydroxylamine are added thereto at 0 and the mixture is shaken. After standing for 24 hours, water is added thereto and the mixture is extracted with methylene chloride. The extract is dried over sodium sulfate and evaporated. The residual oil (1-amino-2-(3,4-dimethoxyphenyl)imidazole) is dissolved in 20 ml of glacial acetic acid. Then. 1.49 g of p-(dimethylamino)benzaldehyde are added thereto. The mixture is left to stand at room temperature for 2 days and evaporated. The crude product is placed on a column loaded with 100 g of silica gel. The product is eluted with methylene chloride/methanol (19:1). The elude is treated with sodium bicarbonate solution and extracted with methylene chloride. The extract is dried over sodium sulfate and evaporated. After crystallization from ether/petroleum ether, there is obtained 1-[[p-(dimethylamino)benzylidene]amino]-2-(3,4-dimethoxyphenyl)imidazole of melting point 149.

Reference： [1]Patent: US4814332,1989,A

15
[ 115053-29-7 ]
[ 72804-96-7 ]
[ 115053-30-0 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; water;	(b) 0.1 g of 1-amino-2-(4-methoxyphenyl)imidazole is dissolved in 10 ml of dichloromethane. The solution is treated portionwise during 8 days with 0.29 g of O-diphenylphosphinylhydroxylamine, evaporated and the residue is suspended in 10 ml of water. The difficultly soluble diphenylphosphinic acid is removed by filtration and the filtrate is placed on a column loaded with Amberlite IRA 400 (chloride), whereupon the column is eluted with water. There is obtained 1,3-diamino-2-(4-methoxyphenyl)imidazolium chloride.

Reference： [1]Patent: US4814332,1989,A

16
[ 72804-96-7 ]
[ 115053-48-0 ]
[ 115053-15-1 ]

Yield	Reaction Conditions	Operation in experiment
	In potassium hydroxide; ethanol; dichloromethane;	(i.b) 43.8 g of O-diphenylphosphinylhydroxylamine are added to 30.1 g of 1-amino-2-phenylimidazole in 2000 ml of dichloromethane. After stirring at room temperature for 3 days an additional 21.9 g of O-diphenylphosphinylhydroxylamine are added. After one day, the mixture is filtered and the filter material is washed four times with 150 ml of dichloromethane each time. The residue is placed on a column loaded with 700 ml of ion-exchanger Amberlite IRA 400 (chloride), whereupon elution is carried out with water. The elude is evaporated and the residue is treated with ethanol and evaporated. After drying in a high vacuum over potassium hydroxide, there is obtained 1,3-diamino-2-phenylimidazolium chloride.
	In potassium hydroxide; ethanol; dichloromethane;	(b) 43.8 of O-diphenylphosphinylhydroxylamine are added to 30.1 g of 1-amino-2-phenylimidazole in 2000 ml of dichloromethane. After stirring at room temperature for 3 days an additional 21.9 g of O-diphenylphosphinylhydroxylamine added. After one day, the mixture is filtered and the filter material is washed four times with 150 ml of dichloromethane each time. The residue is placed on a column loaded with 700 ml of ion-exchanger Amberlite IRA 400 (chloride), whereupon elution is carried out with water. The elude is evaporated and the residue is treated with ethanol and evaporated. After drying in a high vacuum over potassium hydroxide, there is obtained 1,3-diamino-2-phenylimidazolium chloride.

Reference： [1]Patent: US4808727,1989,A
[2]Patent: US4814332,1989,A

17
[ 670-96-2 ]
[ 72804-96-7 ]
[ 4205-05-4 ]
1-amino-2-(p-chlorophenyl)imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one; water;	(a) 32.8 g of sodium hydride (55 percent dispersion in oil) are washed with absolute tetrahydrofuran. A solution of 53.1 g of 2-phenylimidazole in 1500 ml of N-methylpyrrolidone is then added dropwise thereto at 0. The mixture is stirred at 0 for a half hour and at room temperature for about 1.5 hours (until gas evolution is no longer to be observed). Then, 85 g of O-diphenylphosphinylhydroxylamine are added thereto. The mixture is stirred at room temperature for 20 hours and subsequently 910 ml of water are added thereto. The dark solution is stirred at room temperature for 1 hour and then extracted seven times with 300 ml of dichloromethane each time. The extract is dried over sodium sulfate and evaporated. The residual oil is placed on a column loaded with 900 g of silica gel, whereupon the 1-amino-2-phenylimidazole is eluted with dichloromethane/ethanol (85:15). In an analogous manner, from 2-(p-chlorophenyl)imidazole, there is obtained 1-amino-2-(p-chlorophenyl)imidazole of melting point 160 (ethanol/petroleum ether).

Reference： [1]Patent: US4814332,1989,A

18
[ 72804-96-7 ]
[ 52091-37-9 ]
[ 115053-29-7 ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one; water;	(a) 0.18 g of sodium hydride (55 percent dispersion in oil) is washed with tetrahydrofuran. A solution of 0.34 g of 2-(4-methoxyphenyl)-imidazole in 8.3 ml of N-methylpyrrolidone is added dropwise while stirring at 0. As soon as hydrogen no longer forms the mixture is warmed to room temperature. 0.46 g of O-diphenylphosphinylhydroxylamine is added in three portions. After stirring at room temperature for 18 hours, 8 ml of water are added. The mixture is stirred for an additional 1 hour and extracted six times with 20 ml of dichloromethane each time. The extracts are dried over sodium sulfate and evaporated, whereby the N-methyl-pyrrolidone is removed in a high vacuum. The crude product is chromatographed on 5 g of silica gel while eluding with chloroform/ethanol. There is obtained 1-amino-2-(4-methoxyphenyl)imidazole as a dark colored oil.
	With sodium chloride; In tetrahydrofuran;	(a) 9.0 g of sodium hydride (55 percent dispersion in oil) are suspended in 600 ml of absolute tetrahydrofuran. 8.5 g of 2-(p-methoxyphenyl)imidazole are added thereto within 5 minutes. The mixture is stirred until hydrogen is no longer liberated (1 hour). Then, 34.5 g of O-diphenylphosphinylhydroxylamine are added portionwise thereto at 10 and the mixture is stirred at 10 for an additional 40 minutes and then at room temperature for 18 hours. Saturated sodium chloride solution is added thereto at 5 and the mixture is subsequently extracted with methylene chloride/methanol (99.5:0.5). The extract is dried over sodium sulfate and evaporated. There is obtained 1-amino-2-(p-methoxyphenyl)imidazole as a brown oil.

Reference： [1]Patent: US4814332,1989,A
[2]Patent: US4814332,1989,A

19
[ 72804-96-7 ]
[ 52091-37-9 ]
1-(benzylideneamino)-2-(p-methoxyphenyl)imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; benzaldehyde; In 1-methyl-pyrrolidin-2-one; water;	(a) 3.55 g of sodium hydride (55 percent dispersion in oil) are washed with tetrahydrofuran. A solution of 6.5 g of 2-(4-methoxyphenyl)-imidazole in 153 ml of N-methylpyrrolidone is added dropwise thereto at 0. As soon as hydrogen no longer forms a total of 8.8 g of O-diphenylphosphinylhydroxylamine are added portionwise thereto at room temperature. After stirring for 18 hours, the mixture is treated with 150 ml of water, acidified with 80 ml of 2N hydrochloric acid, stirred at 0 for an additional 1 hour and the precipitated diphenylphosphinic acid is removed by filtration. Then, 3.85 ml of benzaldehyde are added to the acidic dark red filtrate and the mixture is stirred for about 20 hours. The dark solution is washed twice with 120 ml of ether each time and adjusted to pH 14 by the addition of 20 ml of 4N sodium hydroxide solution while cooling with ice. The mixture is extracted five times with 150 ml of dichloromethane each time. The extract is dried over sodium sulfate and evaporated, whereby the N-methylpyrrolidone is removed in a high vacuum. The residue is placed on a column loaded with 200 g of silica gel and the product is eluted with dichloromethane/ethanol (98:2) and then crystallized from ethanol. There is obtained 1-(benzylideneamino)-2-(p-methoxyphenyl)imidazole of melting point 155.

Reference： [1]Patent: US4814332,1989,A

20
[ 173944-91-7 ]
[ 72804-96-7 ]
2-(3-Amino-2,4-dioxo-5-pyridin-4-yl-2,3,4,5,5a,9a-hexahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxyphenyl)-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane; In tetrahydrofuran; methanol; ethyl acetate; N,N-dimethyl-formamide;	2-(3-Amino-2,4-dioxo-5-pyridin-4-yl-2,3,4,5,5a,9a-hexahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide To a stirred solution of 80 mg (0.175 mmol) 2-(2,4-Dioxo-5-pyridin-4-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide in 3 mL DMF was added 0.210 mL (0.209 mmol, 1.2 equiv) 1N Sodium bis(trimethylsilyl)amide in THF at 0 C. After stirring 0.5 h, 62 mg (0.262 mmol; 1.5 equiv) O-(diphenyl-phosphinyl)hydroxylamine (Harger, J. C. S. Perkin I, 3284-3288 (1981)) was added and the reaction mixture stirred 16 h at ambient temperature. The reaction mixture was filtered and the filtrate concentrated in vacuo. The crude product was purified by flash chromatography on 5 g silica gel eluted successively with EtOAc (100 mL), DCM/CH3OH (19:1, 100 mL). Appropriate fractions were combined and concentrated in vacuo to give the title compound as a clear glass: low resolution MS (FAB) m/z 474.2 (MH+); TLC Rf=0.31 (DCM/CH3OH, 19:1)).

Reference： [1]Patent: US5739129,1998,A

21
[ 2524-64-3 ]
[ 72804-96-7 ]

Yield	Reaction Conditions	Operation in experiment
36%	With sodium hydroxide; hydroxylamine hydrochloride; In 1,4-dioxane; water; at 0℃; for 0.5h;	To hydroxylamine hydrochloride (15.86 g, 228.2 mmol) in water (35 mL) cooled in an ice- salt bath was added 7.1 N aqueous sodium hydroxide (27.4 mL, 194.4 mmol) followed by 1 ,4-dioxane (100 mL). The solution was vigorously stirred for 15 min and then chlorodiphenylphosphine oxide (20.00 g, 84.52 mmol) was added as a solution in 1,4- dioxane (100 mL). The solution was stirred an additional 15 min as a white precipitate formed. The precipitate was collected and then suspended in cold (0 ) 0.25 N aqueous sodium hydroxide (250 mL). The mixture was stirred for 1 h and then the solid was collected, washed with water (100 mL), and thoroughly dried under vacuum to afford the desired intermediate (7.09 g, 36%) as a white solid. 1H-NMR (300 MHz, DMSO-cfe) § 7.65- 7.74 (m, 4 H), 7.38-7.42 (m, 6 H); 31P-NMR (DMSOd6) xi 23.11 (br s, 1 P).

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 3499 - 3502
[2]Patent: WO2007/64932,2007,A2 .Location in patent: Page/Page column 46-47

22
[ 25091-05-8 ]
[ 72804-96-7 ]
[ 1036738-99-4 ]

Yield	Reaction Conditions	Operation in experiment
59%		Scheme 18. Preparation of rifabutin bisphosphonate conjugate 102.; [00297] Tetrallyl 1-aminomethylenebisphosphonate (96): To a solution of bisphosphonate 6 (2.0 g, 5.95 mmol) in DMF (6 ml.) was added NaH (60% dispersion in mineral oil, 254 mg, 6.35 mmol) portionwise. The solution was stirred for 45 min at room temperature and added to a solution of O-(diphenylphophinyl)hydroxylamine (1.35 g, 5.77 mmol) in THF (40 ml_), cooled in a dry ice/acetone bath. The resulting mixture was stirred for 10 min at the same temperature then 18 h at room temperature. CH2CI2 (40 ml.) was added, the solids were removed by filtration and washed with several portions of CH2CI2. The combined filtrates were concentrated in vacuo and purified by flash chromatography on silica gel using a gradient of 0-5% methanol/ethyl acetate to provide aminobisphosphonate 96 as a clear yellow oil (1.24 g, 59%). 1H NMR (400 MHz, CDCI3) delta 1.69 (bs, 2H), 3.52 (t, J=20.8 Hz, 1 H), 4.64-4.67 (m, 8H), 5.24-5.27 (m, 4H), 5.36-5.42 (m, 4H), 5.92-6.02 (m, 4H).

Reference： [1]Patent: WO2010/19511,2010,A2 .Location in patent: Page/Page column 131-132

23
[ 1237587-86-8 ]
[ 72804-96-7 ]
[ 1237587-87-9 ]

Yield	Reaction Conditions	Operation in experiment
		Reference Production Example 17; Sodium hydride (60% oily; 760 mg) was suspended in tetrahydrofuran (200 mL), and thereto was added dropwise a solution of tert-butyl {2-chloro-5-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]phenyl}carbamate (8.80 g) obtained by Reference Production Example 16 in tetrahydrofuran (50 mL) at room temperature, and then the mixture was stirred at the same temperature for 20 minutes. To the mixture was added O-(diphenylphosphoryl)-hydroxylamine (6.0 g) at room temperature, and the mixture was stirred at the same temperature for 15 hours. To the mixture were added water and ethyl acetate, and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain tert-butyl N-{2-chloro-5-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]phenyl}carbazate (6.58 g).Tert-butyl N-{2-chloro-5-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]phenyl}carbazate: 1H-NMR (CDCl3) delta: 7.55-7.44 (6H, m), 4.07 (1H, d, J=17.1 Hz), 3.68 (1H, d, J=17.1 Hz), 1.41 (9H, br s).
		Reference Production Example 5Sodium hydride (60% oily; 760 mg) was suspended in tetrahydrofuran (200 mL), and thereto was added dropwise a solution of tert-butyl {2-chloro-5-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]phenyl}carbamate (8.80 g) obtained by Reference Production Example 4 in tetrahydrofuran (50 mL) at room temperature, and then the mixture was stirred at the same temperature for 20 minutes. To the mixture was added O-(diphenylphosphoryl)-hydroxylamine (6.0 g) at room temperature, and the mixture was stirred at the same temperature for 15 hours. To the mixture were added water and ethyl acetate, and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain tert-butyl N-{2-chloro-5-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]phenyl}carbazate (6.58 g).Tert-butyl N-{2-chloro-5-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]phenyl}carbazate: 1H-NMR (CDCl3) delta: 7.55-7.44 (6H, m), 4.07 (1H, d, J=17.1 Hz), 3.68 (1H, d, J=17.1 Hz), 1.41 (9H, br s).

Reference： [1]Patent: US2012/29037,2012,A1 .Location in patent: Page/Page column 21
[2]Patent: US2012/29040,2012,A1 .Location in patent: Page/Page column 16

24
[ 72804-96-7 ]
[ 66-77-3 ]
[ 1402800-64-9 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 9334 - 9337,4

25
[ 72804-96-7 ]
(S)-N-cyclohexyl-4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepine [ No CAS ]
C₂₈H₂₉N₂⁽¹⁺⁾*C₁₂H₁₀O₂P^(1-) [ No CAS ]

Reference： [1]Synlett,2013,vol. 24,p. 2067 - 2072

26
[ 72804-96-7 ]
(S)-N-(4-methoxyphenyl)-4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepine [ No CAS ]
C₂₉H₂₅N₂O⁽¹⁺⁾*C₁₂H₁₀O₂P^(1-) [ No CAS ]

Reference： [1]Synlett,2013,vol. 24,p. 2067 - 2072

27
[ 72804-96-7 ]
(S)-N-isopropyl-4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepine [ No CAS ]
C₂₅H₂₅N₂⁽¹⁺⁾*C₁₂H₁₀O₂P^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at 20℃;	(S)-N-Isopropyl-2,7-dihydrodinaphtho[2,1-c;1',2'-e]azepine (1.0 g, 2.96 mmol) was dissolved in DCM (30 mL). DppONH2 (758 mg, 3.25 mmol) was added as a solid in a single portion and the resulting white slurry was stirred overnight at room temperature (TLC indicated complete consumption of the starting material). The mixture was filtered through a pad of Celite and concentrated in vacuo to give the hydrazinium diphenylphosphinate as a hygroscopic yellow foam. The crude compound was redissolved in aminimum amount of DCM and a saturated solution of sodium tetraphenylborate (1.11 g, 3.25 mmol) in MeCN was added. Copious precipitation of a colourless solid ensued. The title compound 23 was isolated via filtration as a colourless powder

Reference： [1]Synlett,2013,vol. 24,p. 2067 - 2072

28
[ 5470-11-1 ]
[ 1499-21-4 ]
[ 72804-96-7 ]

Yield	Reaction Conditions	Operation in experiment
		Compound 64.1. (Aminooxy)diphenylphosphine oxide. Into a 500-mL three neck round-bottom flask, was placed a solution of hydroxylamine hydrochloride (30.0 g, 432 mmol) in H20/dioxane (90/45 mL). The solution was cooled to 0-5 C, then sodium bicarbonate (36.5 g, 434 mmol) was added portion-wise over 10 min and the mixture was stirred at 0-5 C for 30 min. A solution of diphenylphosphinoyl chloride (41.0 g, 173 mmol) in dioxane (45 mL) was added drop-wise at 0-5C over 30 min, then the resulting mixture was stirred for an additional 2 h at ambient temperature. The resulting solids were collected by filtration and washed with water (200 mL), NaOH (0.25 M, 200 mL) and PE (200 mL). The product was dried to yield the title und as a white solid (20 g, crude).

Reference： [1]Patent: WO2014/8197,2014,A1 .Location in patent: Page/Page column 134; 135

29
[ 72804-96-7 ]
[ 934-05-4 ]
[ 1208361-39-0 ]

Yield	Reaction Conditions	Operation in experiment
77%		To a solution of 4-bromo-1H-pyrrole-2-carboxylic acid methyl ester (3.5 g, 17.2 mmol, 1 eq) in DMF (120 mL) was added NaH (0.82 g, 20.6 mmol, 1.2 eq) at 0 C., and the mixture was stirred at 0 C. for 1 h, followed by the addition of o-(diphenylphosphinyl)-hydroxylamine (6 g, 25.8 mmol). The reaction mixture was stirred for another 1 h, then neutralized with 20% NH4Cl solution, and extracted with EA. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated by evaporation. The residue was purified by column chromatography on silica gel (PE/EA=4:1) to give 1-amino-4-bromo-1H-pyrrole-2-carboxylic acid methyl ester (2.9 g, yield 77%) as a light yellow solid. MS (ES+) requires: 218, 220. found 219, 221 [M+H]+; purity: 97%.

Reference： [1]Patent: US2015/111887,2015,A1 .Location in patent: Paragraph 0179; 0180

30
[ 72804-96-7 ]
[ 226410-00-0 ]
[ 753447-98-2 ]

Yield	Reaction Conditions	Operation in experiment
91%		To a suspension of sodium hydride (60 percent, 1.5 g, 37.5 mmol) in DMF (250 mL) was added <strong>[226410-00-0]methyl 3-chloro-1H-pyrrole-2-carboxylate</strong> (5.0 g, 31.3 mmol) at 0 C., and the mixture was stirred for 25 min, followed by the addition of O-(diphenylphosphoryl)hydroxylamine (10.0 g, 43.75 mmol). The reaction mixture was stirred at RT for 4 h and quenched by aq. Na2SO3 solution. After stirred for another 5 min, the mixture was extracted with EtOAc (3×300 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give crude product as a brown oil, which was purified by chromatography purification on silica gel (PE:EA=4:1) to obtain the title compound (5.00 g, 91%) as a white solid. MS (ES+) C6H7ClN2O2 requires: 174, 176. found: 175, 177 [M+H]+.

Reference： [1]Patent: US2015/111887,2015,A1 .Location in patent: Paragraph 0194; 0195

31
[ 72804-96-7 ]
[ 19524-06-2 ]
[ 1533440-88-8 ]

Yield	Reaction Conditions	Operation in experiment
		Compound 64.2. l-Amino-4-bromopyridin-l-ium iodide. Into a 250-mL round- bottom flask, was placed a solution of 4-bromopyridine hydrochloride (13.8 g, 71.0 mmol) in water (50 mL). The solution was cooled to 0-5 C then sodium bicarbonate (12.0 g, 141mmol) was added portion-wise over 10 min and the mixture was stirred at 0-5C for 30 min. The mixture was extracted with DCM (4 x 50 mL) and the combined organic layers were washed with brine (50 mL), dried (Na2S04), and filtered. The filtrate was placed into a 500-mL round-bottom flask, then purged and maintained with an inert atmosphere of nitrogen. (Aminooxy)diphenylphosphine oxide (compound 64.1, 20 g, -70% purity, 60 mmol) was added and the mixture was stirred overnight at room temperature. The reaction was carefully quenched with aqueous HI (8 mL, 45%) and stirred for 30 min. The solids were collected by filtration, and washed with DCM (200 mL) and hexanes (200 mL) to yield the title compound as a brown solid (15 g, crude).

Reference： [1]Patent: WO2015/95767,2015,A1 .Location in patent: Page/Page column 150

32
[ 767-15-7 ]
[ 72804-96-7 ]
1-amino-4,6-dimethyl-1H-pyrimidin-2-ylideneammonium diphenylphosphinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	In dichloromethane; at 0℃; for 24h;Inert atmosphere;	The solution of 2-amino-4,6-dimethylpyrimidine (4.18 g, 34.0 mmol) in dry dichloromethane (80 mL) was put under argon and cooled in an ice-^ath to 0 C. Then to the solution 8.8 g (34.0 mmol) of <strong>[72804-96-7]O-(diphenylphosphinyl)hydroxylamine</strong> were added portionwise. The resulted white suspension was stirred for 24 hours, then the mixture was slowly brought to room temperature (without removing the ice-^ath). White solid product thus formed was filtered on Schott funnel. The filtrate was concentrated, obtained yellow solid was triturated with dichloromethane and filtered-off (second crop). Combined solids were dried under reduced pressure to obtain 7.78 g of the title product (yield 64%). MS-ESI: (m/z) calculated for C6HioN4 [M+H]": 139.09, found 139.1 (iminium cation); calculated for C12H11O2P [M-H]": 217.04, found 217.1 (diphenylphosphinate anion).

Reference： [1]Patent: WO2015/177688,2015,A1 .Location in patent: Page/Page column 19; 20

33
[ 72804-96-7 ]
5,7-dimethyl-2-(1-methyl-2-phenyl-1H-benzo[d]imidazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrimidine [ No CAS ]
5,7-dimethyl-2-(1-methyl-2-phenyl-1H-benzo[d]imidazol-6-yl)-[1,2,4]triazolo[1,5-a]pyrimidine [ No CAS ]

Reference： [1]Patent: WO2015/177688,2015,A1

34
[ 72804-96-7 ]
7-{5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-2-phenylimidazo[1,2-a]pyrimidine [ No CAS ]

Reference： [1]Patent: WO2015/177688,2015,A1

35
[ 72804-96-7 ]
5,7-dimethyl-2-(2-phenyl-1H-benzo[d]imidazol-5-yl)-[1,2,4]triazolo-[1,5-a]pyrimidine [ No CAS ]

Reference： [1]Patent: WO2015/177688,2015,A1

36
[ 72804-96-7 ]
5,7-dimethyl-2-[2-(pyridin-2-yl)-1H-benzo[d]imidazol-5-yl]-[1,2,4]triazolo[1,5-a]pyrimidine [ No CAS ]

Reference： [1]Patent: WO2015/177688,2015,A1

37
[ 13134-38-8 ]
[ 72804-96-7 ]
1-amino-2-imino-3,6-dimethyl-2,3-dihydro-1-pyrazinium diphenylphosphinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	In dichloromethane; at 20℃; for 20h;	To the solution of thus obtained <strong>[13134-38-8]2-amino-3,6-dimethylpyrazine</strong> (4.0 g, 32.5 mmol) in drydichloromethane (150 mL), 6.89 g (29.5 mmol) of O-(diphenylphosphinyl)hydroxylaminewere added at room temperature. The whole was stirred at room temperature for 20 hours. The mixture was concentrated to the constant mass and after addition of isopropanol (50 mL)- toluene (10 mL) mixture concentrated again to remove traces of water. Dry residue was triturated with ethyl ether. Obtained solid was filtered-off and dried under reduced pressure.6.91 g of the title product as a brown solid were obtained (yield 66%). MS-ESI: (mlz) calculated for C6H10N4 [M+H]: 139.09, found 139.1 (pyrazinium cation); calculated for C12H11O2P [M-H]: 217.04, found 217.1 (diphenylphosphinate anion).

Reference： [1]Patent: WO2015/177688,2015,A1 .Location in patent: Paragraph 20

38
[ 72804-96-7 ]
[ 17325-26-7 ]
[ 865444-80-0 ]

Yield	Reaction Conditions	Operation in experiment
24 g		To a solution of compound 3H-lmidazole-4-carboxylic acid methyl ester 32 (30.0 g0,24 mol) in THF (1,0 L)was dropwise added LiHMDS (239 mL, 1OM in THF, 2,4 mol) over 2 hours at -78 0C Then the reaction mixture was stirred at -78 C for another two hours and allowed to warm to 10 C. Compound B (60.0 g, 0.26 mol) was added at this temperature. Then the mixture reaction was stirred at ambient temperature overnight. After quenching with water (250 mL), the reaction mixture was concentrated. The crude product was purified by column chromatography on silica gel(DCM/MeOH= 20/1) to afford compound 46 (24 g, 73% yield) as a solid.1H NMR (400 MHz, DMSO-d6): 57.82 (s, IH), 7.51 (s, 1H), 6.20 (s, 2H), 3.79 (5, 3H). MS Calcd.: 382; MS Found: 383 ([M+Hfl. MS Calcd.: 141; MS Found: 142 ([M+Hfl.

Reference： [1]Patent: WO2017/5786,2017,A1 .Location in patent: Page/Page column 57; 58

39
benzhydryl 1-hydroxycyclopropane-1-carboxylate [ No CAS ]
[ 72804-96-7 ]
benzhydryl 1-(aminooxy)cyclopropane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium t-butanolate; In tetrahydrofuran; at 0 - 10℃; for 1h;Inert atmosphere;	A synthesis of this compound has also been reported by Yamawaki et al (Bioorg. Med. Chem. 15 (2007), 6716).To a stirred mixture of benzhydryl 1-hydroxycyclopropane-1-carboxylate(2.00 kg, 7.46 mol, 1 eq) and (aminooxy)diphenylphosphine oxide (2.08 kg, 8.93 mol, 1.2 eq) in THF (20 L) was added sodiumtert-butoxide (0.86 kg, 8.96 mol, 1.2 eq) at 0-10under nitrogen. The resulting mixture was stirred at 0-10for 60 min.5% aq. NaCl (12 L) was added and the mixture was stirred at 15-25for 30 min. The precipitate was removed by filtration and washed with EtOAc (4 L). The filtrate was stirred for 5 min and the phases were separated. The aqueous layer was extracted with EtOAc (2x 10 L). The combined organic phases were washed with 5% aq. NaCl (2x 6 L) to give a solution of benzhydryl 1-(aminooxy)cyclopropane-1-carboxylate in THF/EtOAc (39.75 kg, 68.9% purity) which was used in the next step directly without further purification.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 748 - 755

40
[ 72804-96-7 ]
5-(1,1-difluoroethyl)pyrrolidin-2-one [ No CAS ]
1-amino-5-(1,1-difluoroethyl)pyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30 mg		To a solution of 5-(1,1-difluoroethyl)pyrrolidin-2-one (60 mg, 0.4 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (60%, 24 mg, 0.6 mmol) at 0 C. After addition, the mixture was stirred at 0 C. for 30 min and O-(diphenylphosphoryl)hydroxylamine (141 mg, 0.6 mmol) was added. The reaction mixture was stirred at 25 C. for 16 h and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by preparative TLC (100% ethyl acetate in petroleum ether, Rf=0.4) to afford 1-amino-5-(1,1-difluoroethyl)pyrrolidin-2-one (30 mg, 45%) as a yellow oil. LCMS RT=0.716 min, m/z=165.1 [M+H]+.

Reference： [1]Patent: US2018/153831,2018,A1 .Location in patent: Paragraph 0272-0274

41
[ 72804-96-7 ]
ethyl 4-isopropyl-2-methyl-1H-imidazole-5-carboxylate [ No CAS ]
ethyl 1-amino-4-isopropyl-2-methyl-1H-imidazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.07 g		To a cooled (-10 C.) solution of ethyl 4-isopropyl-2-methyl-1H-imidazole-5-carboxylate (3.72 g, 19.0 mmol) in DMF (30 mL) was added a solution of LiHMDS (lithium hexamethyldisilazide) (1 M in THF, 20.86 mL). The mixture was stirred at -10 C. for 30 minutes. Then a solution of (aminooxy)diphenylphosphine oxide (5.31 g, 22.8 mmol) in DMF (20 mL) was added dropwise. The mixture was stirred at -10 C. for 1 hour. Water (50 mL) was added and the mixture was extracted with ethyl acetate (50 mL2). The organic layer was washed with water (50 mL3), brine (50 mL), dried over Na2SO4, filtered and concentrated to give ethyl 1-amino-4-isopropyl-2-methyl-1H-imidazole-5-carboxylate (3.07 g).

Reference： [1]Patent: US2018/179200,2018,A1 .Location in patent: Paragraph 0357; 0358

42
[ 72804-96-7 ]
cis-3-[tert-butyl(dimethyl)silyl]oxy-5-phenylpyrrolidin-2-one [ No CAS ]
cis-1-amino-3-[tert-butyl(dimethyl)silyl]oxy-5-phenylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of cis-3-[tert-butyl(dimethyl)silyl]oxy-5-phenyl-pyrrolidin-2-one (12.4 g, 42.8 mmol) in N,N-dimethylformamide (400 mL) was slowly added sodium hydride (60%, 2.6 g, 64.1 mmol) at 0 C. After addition, the mixture was stirred at 0 C. for 20 min and subsequently O-(diphenylphosphoryl)hydroxylamine (14.9 g, 64.1 mmol) was added. The reaction mixture was stirred at 25 C. for 16 h and then filtered. The filtrate was concentrated under reduced pressure to afford the crude cis-1-amino-3-[tert-butyl(dimethyl)silyl]oxy-5-phenyl-pyrrolidin-2-one as a yellow oil (9.5 g, 73%), used in the next step without further purification. LCMS RT=0.877 min, m/z=307.0 [M+H]+.LCMS (5 to 95% acetonitrile in water+0.03% trifluoacetic acid over 1.5 mins) retention time 0.877 mm, ESI+ found [M+H]=307.0.

Reference： [1]Patent: US2018/170927,2018,A1 .Location in patent: Paragraph 0525; 0526

43
[ 72804-96-7 ]
[ 500890-03-9 ]
ethyl 1-amino-2,4-dimethyl-1H-imidazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%		Step 4: Preparation of ethyl 1-amino-2,4-dimethyl-1H-imidazole-5-carboxylate LiHMDS (8.5 mL, 1M in THF) was added dropwise into a mixture of ethyl 2,4-dimethyl-1H-imidazole-5-carboxylate (1.3 g, 7.73 mmol) and N,N-dimethylformamide (200 mL) with stirring at -10 C. in a dry ice bath under nitrogen. The resulting solution was stirred for 30 min at -10 C. To this was added amino diphenylphosphinate (2.2 g, 9.43 mmol) in portions at 0 C. The resulting solution was allowed to react, with stirring, for an additional 12 h at room temperature. The resulting solution was diluted with of water, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column eluting with dichloromethane/methanol (10/1) to afford the title compound (1.0 g, 71%) as a light yellow solid. LCMS [M+H+] 184.

Reference： [1]Patent: US2019/284179,2019,A1

44
[ 72804-96-7 ]
[ 23785-21-9 ]
[ 1179361-84-2 ]

Reference： [1]Patent: WO2022/28598,2022,A1 .Location in patent: Paragraph 00307; 00356

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P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 72804-96-7 ] {[proInfo.proName]}

Quality Control of [ 72804-96-7 ]

Related Doc. of [ 72804-96-7 ]

Product Details of [ 72804-96-7 ]

Calculated chemistry of [ 72804-96-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 72804-96-7 ]

Application In Synthesis of [ 72804-96-7 ]

[ 72804-96-7 ] Synthesis Path-Upstream 1~5

[ 72804-96-7 ] Synthesis Path-Downstream 1~44

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry