[ CAS No. 7424-91-1 ] {[proInfo.proName]}

Name: 7424-91-1|Methyl 3,3-dimethoxypropanoate|97%
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Quality Control of [ 7424-91-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 7424-91-1 ]

Product Details of [ 7424-91-1 ]

CAS No. :	7424-91-1	MDL No. :	MFCD00010650
Formula :	C₆H₁₂O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SMCVPMKCDDNUCQ-UHFFFAOYSA-N
M.W :	148.16	Pubchem ID :	81924
Synonyms :		Chemical Name :	Methyl 3,3-dimethoxypropanoate

Calculated chemistry of [ 7424-91-1 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.83
Num. rotatable bonds :	5
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	34.41
TPSA :	44.76 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) :	-7.26 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.98
Log Po/w (XLOGP3) :	-0.08
Log Po/w (WLOGP) :	0.17
Log Po/w (MLOGP) :	-0.05
Log Po/w (SILICOS-IT) :	0.2
Consensus Log Po/w :	0.44

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.38
Solubility :	62.0 mg/ml ; 0.419 mol/l
Class :	Very soluble
Log S (Ali) :	-0.41
Solubility :	57.9 mg/ml ; 0.391 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.65
Solubility :	33.6 mg/ml ; 0.226 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.9

Safety of [ 7424-91-1 ]

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

Application In Synthesis of [ 7424-91-1 ]

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

Upstream synthesis route of [ 7424-91-1 ]
Downstream synthetic route of [ 7424-91-1 ]

[ 7424-91-1 ] Synthesis Path-Upstream 1~15

1
[ 7424-91-1 ]
[ 17356-08-0 ]
[ 141-90-2 ]

Reference： [1] Synthesis, 1986, # 12, p. 1041 - 1044

2
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[ 107-31-3 ]
[ 3167-50-8 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: With sodium methylate In 1,4-dioxane; methanolReflux; Large scale Stage #2: at 20℃; Large scale Stage #3: Large scale	Example 9: Step A10 : Preparation of 2-aminopyrimidine-5-carboxylic acid (9b) 1 kg of methyl 3,3-dimethoxypropanoate was dissolved in 7 L of 1 ,4-dioxane. 1 .58 kg of sodium methoxide solution (30 wpercent in methanol) were added. The mixture was heated to reflux, and ap. 4.9 kg of distillate were removed. The resulting suspension was cooled to r.t., and 0.5 kg of methyl formate was added. The reaction mixture was stirred overnight, then 0.71 kg of guanidine hydrochloride was added, and the reaction mixture was stirred at r.t. for 2 h. The reaction mixture was then heated to reflux, and stirred for 2 h. 13.5 L of water were added, followed by 0.72 kg of aqueous sodium hydroxide solution (45 wpercent). The reaction mixture was heated at reflux for additional 0.5 h, and then cooled to 50°C. 0.92 kg of aqueous hydrochloric acid (25 wpercent) were added until pH 6 was reached. Seeding crystals were added, and additional 0.84 kg of aqueous hydrochloric acid (25 wpercent) were added at 50°C until pH 2 was reached. The mixture was cooled to 20°C and stirred overnight. The suspension was filtered, the collected solids washed twice with water, then twice with methanol, yielding 0.61 kg (65percent).

Reference： [1] Patent: WO2016/71435, 2016, A2, . Location in patent: Page/Page column 54-55

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[ 50-01-1 ]
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Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: With sodium methylate In 1,4-dioxane; methanolReflux; Large scale Stage #2: Large scale Stage #3: Large scale	1 kg of methyl 3,3-dimethoxypropanoate was dissolved in 7 L of 1 ,4-dioxane. 1 .58 kg of sodium methoxide solution (30 wpercent in methanol) were added. The mixture was heated to reflux, and ap. 4.9 kg of distillate were removed. The resulting suspension was cooled to r.t., and 0.5 kg of methyl formate was added. The reaction mixture was stirred overnight, then 0.71 kg of guanidine hydrochloride was added, and the reaction mixture was stirred at r.t. for 2 h. The reaction mixture was then heated to reflux, and stirred for 2 h. 13.5 L of water were added, followed by 0.72 kg of aqueous sodium hydroxide solution (45 wpercent). The reaction mixture was heated at reflux for additional 0.5 h, and then cooled to 50°C. 0.92 kg of aqueous hydrochloric acid (25 wpercent) were added until pH 6 was reached. Seeding crystals were added, and additional 0.84 kg of aqueous hydrochloric acid (25 wpercent) were added at 50 until pH 2 was reached. The mixture was cooled to 20 and stirred overnight. The suspension was filtered, the collected solids washed twice with water, then twice with methanol, yielding 0.61 kg (65percent).

Reference： [1] Patent: WO2016/71426, 2016, A1, . Location in patent: Page/Page column 36; 37

4
[ 7424-91-1 ]
[ 123-38-6 ]
[ 35351-35-0 ]

Reference： [1] Journal of Organic Chemistry, 2007, vol. 72, # 23, p. 8820 - 8823

5
[ 67-56-1 ]
[ 1165952-92-0 ]
[ 7424-91-1 ]
[ 102-52-3 ]
[ 108-59-8 ]

Reference： [1] Liebigs Annalen der Chemie, 1990, # 2, p. 185 - 188
[2] Liebigs Annalen der Chemie, 1990, # 2, p. 185 - 188
[3] Liebigs Annalen der Chemie, 1990, # 2, p. 185 - 188

6
[ 67-56-1 ]
[ 123331-77-1 ]
[ 7424-91-1 ]
[ 102-52-3 ]

Reference： [1] Monatshefte fuer Chemie, 1990, vol. 121, p. 203 - 207
[2] Monatshefte fuer Chemie, 1990, vol. 121, p. 203 - 207

7
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[ 34846-90-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	at 160℃; for 6 h;	Example 2: Preparation of methyl 3-methoxyprop-2-enoate Under an atmosphere of nitrogen, 0.2 g (2 mmol) of methanesulfonic acid (Fluka) was added to 150 g of a filtrate, analogously obtained as described in example 1 (about 85percent, 0.86 mol of methyl 3,3-dimethoxypropionate), in a distillation apparatus with round-bottomed flask. Under constant flow of nitrogen, the mixture was slowly heated to 160 °C, and the methanol formed was directly distilled off. After 6 hours, the heat supply was stopped. The methyl 3-methoxy- prop-2-enoate obtained in this manner was 88percent pure (GC) and was purified by rectification at 10 kPa. The yield was 85 g (85percent) of methyl 3-methoxyprop-2-enoate (Ki_{0 k}p_a = 95⁰C) with a purity of 99percent (GC).; Example 6: Preparation of methyl 3-methoxyprop-2-enoate After distillative removal of the unreacted trimethyl ortho formate from example 1, 4.4 t (30 kmol) of the methyl 3,3-dimethoxypropionate thus obtained were reacted under an atmosphere of nitrogen with 6 kg (62 mol) of methanesulfonic acid analogously to example 2. <n="10"/>Rectification at 10 kPa gave 2.4 t (21 kmol, 69percent based on trimethyl orthoformate employed) of methyl 3-methoxyprop-2-enoate (Ki_{0 k}p_a = 95 °C) in a purity of 93percent (GC).
82%	at 150 - 160℃; for 4 h;	In a 100 ml three-necked flask, 97 g of BJ02, 5 g of potassium bisulfate and 50 g were addedPolyethylene glycol dimethyl ether, Heated to 150 ~ 160 , 4 hours of stirring insulation, vacuum pump distillation was 46.5gMethyl 3-methoxyacrylate, Yield 82percent, GC normalized content of 98.7percent
535 g	at 190℃; for 20 h;	Raw material composition of this embodiment: methyl acrylate 560g, methanol 716g, cobalt oxide 2.24g, indium oxide 8.96g, concentrated sulfuric acid 17.6g;Preparation Process: Methyl acrylate, methanol and synthetic catalyst were added to the reactor and stirred well to keep the reaction liquid warm to 50°C.The reactor was filled with nitrogen and oxygen so that the partial pressures of nitrogen and oxygen were 0.4 MPa and the reaction was started. The reaction time was 16 h.When the content of methyl acrylate in the reaction solution was 3percent, the reaction was completed and the etherification reaction product was added.The etherification reaction product is filtered to recover the catalyst, petroleum ether is added to the filtrate, and the mixture is evenly stirred and allowed to stand for stratification.The upper layer is a petroleum ether layer. Atmospheric distillation recovers petroleum ether to give intermediate product methyl 3,3-dimethoxypropionate 703g.From the lower aqueous phase, methanol and methyl acrylate are recovered and applied.Separated methyl 3,3-dimethoxypropionate into the cracking kettle, then slowly added 17.6 g of concentrated sulfuric acid,The temperature was further increased to 190° C., the cleavage reaction was carried out for 20 h, and all lysates were collected to obtain 430 g of crude MAME.The crude MAME was added to the rectification vessel to recover the distillation product by vacuum distillation and weighed to obtain 478 g of the target product methyl 3-methoxyacrylate.The target product obtained in this example was 535 g, and the yield based on methyl acrylate was 82.4percent. The product purity was 95.8percent.

Reference： [1] Patent: WO2009/56293, 2009, A1, . Location in patent: Page/Page column 8-9
[2] Patent: CN105418421, 2016, A, . Location in patent: Paragraph 0020; 0023
[3] Patent: WO2009/56293, 2009, A1, . Location in patent: Page/Page column 8
[4] Patent: WO2009/56293, 2009, A1, . Location in patent: Page/Page column 8
[5] Patent: WO2009/56293, 2009, A1, . Location in patent: Page/Page column 8
[6] Patent: CN107879936, 2018, A, . Location in patent: Paragraph 0016-0020

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[ 67-56-1 ]
[ 292638-85-8 ]
[ 7424-91-1 ]
[ 34846-90-7 ]

Reference： [1] Tetrahedron, 2006, vol. 62, # 42, p. 9846 - 9854

9
[ 463-51-4 ]
[ 149-73-5 ]
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[ 79-20-9 ]
[ 34846-90-7 ]

Reference： [1] Patent: WO2009/56293, 2009, A1, . Location in patent: Page/Page column 7-8

10
[ 7424-91-1 ]
[ 80370-42-9 ]

Reference： [1] Patent: WO2006/97691, 2006, A1, . Location in patent: Page/Page column 32

11
[ 7424-91-1 ]
[ 109-94-4 ]
[ 80370-42-9 ]

Reference： [1] Synthesis, 1986, # 5, p. 400 - 402

12
[ 7424-91-1 ]
[ 501-53-1 ]
[ 54755-77-0 ]

Reference： [1] European Journal of Organic Chemistry, 2007, # 28, p. 4646 - 4650

13
[ 7424-91-1 ]
[ 19501-58-7 ]
[ 172595-68-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	at 70℃; for 4.5 h;	(Intermediate Example 38) 5-Methoxy-1-methyl-1H-indole-3-carboxylic acid 4-Methoxyphenylhydrazine hydrochloride (200 mg) and methyl 3,3-dimethoxypropionate (194 mg) were added to acetic acid (8.0 ml) and stirred for 4.5 hours at 70°C. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (eluding solvent; ethyl acetate: n-hexane 1: 5 --> 1: 3) to give methyl 5-methoxy-1H-indole-3-carboxylate (259 mg, Y.: 97percent). ¹H NMR; (DMSO-d₆) δ (ppm): 3.8 (3H, s), 3.9 (3H, s), 6.8 (1H, dd), 7.4 (1H, d), 7.5 (1H, d), 8.0 (1H, s), 11.8 (1H, brs). ESI/MS (m/z): 204 (M-H)^-.

Reference： [1] Patent: EP1595866, 2005, A1, . Location in patent: Page/Page column 18

14
[ 7424-91-1 ]
[ 107-31-3 ]
[ 50-01-1 ]
[ 308348-93-8 ]

Yield	Reaction Conditions	Operation in experiment
61%	Stage #1: With sodium hydride In tetrahydrofuran at 0 - 50℃; for 4 h; Stage #2: at 100℃; for 3 h; Inert atmosphere	Methyl 3,3-dimethoxypropanoate ( 1 00 g, 675 mmol) and methyl formate (8 1 g, 1 350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60percent dispersion; 32.4 g, 8 1 0 mmol, 1 .2 eq.) was then added slowly in portions at 0 °C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 °C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification. The crude enolate from step 1 was dissolved in DMF (200 mL), and guanidine hydrochloride (64 g, 670 mmol) was added. The mixture was heated at 1 00 °C under Ni for 3 h. After cooling to rt, water was added and the mixture was cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum to give the desired product (63 g, 61 percent yield for 2 steps).
61%	Stage #1: With sodium hydride In tetrahydrofuran at 0 - 50℃; for 4 h; Stage #2: at 100℃; for 3 h; Inert atmosphere	Methyl 3,3-dimethoxypropanoate ( 1 00 g, 675 mmol) and methyl formate (8 1 g, 1 350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60percent dispersion; 32.4 g, 8 1 0 mmol, 1 .2 eq.) was then added slowly in portions at 0 °C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 °C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification. The crude enolate from step 1 was dissolved in DMF (200 mL), and guanidine hydrochloride (64 g, 670 mmol) was added. The mixture was heated at 1 00 °C under N2 for 3 h. After cooling to rt, water was added and the mixture was cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum to give the desired product (63 g, 61 percent yield for 2 steps).

Reference： [1] Patent: WO2013/127267, 2013, A1, . Location in patent: Page/Page column 82
[2] Patent: WO2013/127268, 2013, A1, . Location in patent: Page/Page column 60

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[ 7424-91-1 ]
[ 29124-57-0 ]
[ 1220418-77-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 16, p. 5836 - 5857

[ 7424-91-1 ] Synthesis Path-Downstream 1~75

1
[ 7424-91-1 ]
[ 5788-17-0 ]

Reference： [1]Patent: US2526008,1949,
[2]Patent: US2526007,1949,

2
[ 7424-91-1 ]
[ 6191-98-6 ]

Yield	Reaction Conditions	Operation in experiment
92%		Intermediate VIIId7-(Bromomethyl)-8-fluoro-l-methylquinolin-2(lH)-one: <n="67"/>Preparation of 3,3-dimethoxypropanoic acid: [0218] A mixture of methyl 3,3-dimethoxypropanoate (5 g, 33.74 mmol), LiOH (4.03 g, 168.7 mmol) in Methanol:THF: Water (20:20:20) was heated at 800C for 2h. The reaction mixture was acidified using 10% HCl and extracted with CH2Cl2 and dried over Na2SO4. The crude product was evaporated to dryness to give acid (4.2 g, 92%).
80 - 100%		Example 18 Preparation of (+)-2-(2-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)propan-2-ol, L-tartrate salt Step A: To a solution of aqueous 2N sodium hydroxide (100 mL) was added methyl 3,3-dimethoxy propionate (25.0 g, 0.17 mol). The reaction solution was stirred at 50 C. for 1 hour and then cooled to room temperature. The resultant reaction mixture was acidified with 6N hydrochloric acid to pH 1 and extracted with dichloromethane three times. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to give the desired acid (22.5 g, quantitative) as a clear colorless oil, which was used in the next step without further purification: 1H NMR (CDCl3, 300 MHz) delta 4.83 (t, J=5.7 Hz, 1H), 3.39 (s, 6H), 2.71 (d, J=5.7 Hz, 2H).; Example 53 Preparation of (+/-)-8-methoxy-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepine, maleate salt Step A: To a solution of aqueous 2N sodium hydroxide (100 mL) was added methyl 3,3-dimethoxy propionate (25.0 g, 0.17 mol). The reaction solution was stirred at 50 C. for 1 h and then cooled to room temperature. The resultant reaction mixture was acidified with 6 N hydrochloric acid to pH 1 and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to give the desired acid (18.0 g, 80%) as a clear colorless oil, which was used in the next step without further purification: 1H NMR (CDCl3, 300 MHz) delta 4.83 (t, J=5.7 Hz, 1H), 3.39 (s, 6H), 2.71 (d, J=5.7 Hz, 2H).;' Example 54 Preparation of (+/-)-2-ethyl-8-methoxy-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepine, maleate salt Step A: To a solution of aqueous 2N sodium hydroxide (100 mL) was added methyl 3,3-dimethoxy propionate (25.0 g, 0.17 mol). The reaction solution was stirred at 50 C. for 1 hour and then cooled to room temperature. The resultant reaction mixture was acidified with 6 N hydrochloric acid to pH 1 and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to give the desired acid (18.0 g, 80%) as a clear colorless oil, which was used in the next step without further purification: 1H NMR (CDCl3, 300 MHz) delta 4.83 (t, J=5.7 Hz, 1H), 3.39 (s, 6H), 2.71 (d, J=5.7 Hz, 2H).; Example 56 Preparation of 4-(5-phenyl-2-(2,2,2-trifluoroethyl)-2,3,4,5,-tetrahydro-1H-benzo[c]-azepin-8-yl)morpholine, maleate salt Step A: To a solution of aqueous 2N sodium hydroxide (100 mL) was added methyl 3,3-dimethoxy propionate (25.0 g, 0.17 mol). The reaction solution was stirred at 50 C. for 1 hour and then cooled to room temperature. The resultant reaction mixture was acidified with 6 N hydrochloric acid to pH 1 and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to give the desired acid (18.0 g, 80%) as a clear colorless oil, which was used in the next step without further purification: 1H NMR (CDCl3, 300 MHz) delta 4.83 (t, J=5.7 Hz, 1H), 3.39 (s, 6H), 2.71 (d, J=5.7 Hz, 2H).Example 57 Preparation of (-)-4-(2-ethyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)morpholine, maleate salt and (+)-4-(2-ethyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)morpholine, maleate salt Step A: To a solution of aqueous 2N sodium hydroxide (100 mL) was added methyl 3,3-dimethoxy propionate (25.0 g, 0.17 mol). The reaction solution was stirred at 50 C. for 1 hour and then cooled to room temperature. The resultant reaction mixture was acidified with 6 N hydrochloric acid to pH 1 and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to give the desired acid (18.0 g, 80%) as a clear colorless oil, which was used in the next step without further purification: 1H NMR (CDCl3, 300 MHz) delta 4.83 (t, J=5.7 Hz, 1H), 3.39 (s, 6H), 2.71 (d, J=5.7 Hz, 2H).; Example 59 Preparation of (+)-2-(8-morpholino-5-phenyl-4,5-dihydro-1H-benzo[c]azepin-2(3H)-yl)ethanol, L-tartrate salt Step A: To a solution of aqueous 2N sodium hydroxide (100 mL) was added methyl 3,3-dimethoxy propionate (25.0 g, 0.17 mol). The reaction solution was stirred at 50 C. for 1 hour and then cooled to room temperature. The resultant reaction mixture was acidified with 6 N hydrochloric acid to pH 1 and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to give the desired acid (18.0 g, 80%) as a clear colorless oil, which was used in the next step without further purification: 1H NMR (CDCl3, 300 MHz) delta 4.83 (t, J=5.7 Hz, 1H), 3.39 (s, 6H), 2.71 (d, J=5.7 Hz, 2H).; Example 62 Preparation of 2,6-difluoro-4-(8-methoxy-2-methyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-yl)phenol, citrate salt Step A: To a solution of aqueous 2 N sodium hydroxide (100 mL) was added methyl 3,3-dimethoxy propionate (25.0 g, 0.17 mol). The reaction solution was stirred at 50 C. for 1 hour and then cooled to room tempe...
78%	In sodium hydroxide; water;	PREPARATION 13 50 g (0.33 mol.) of Methyl 3,3-dimethoxy-propanoate in 200 ml of 2N NaOH solution in water were refluxed 2 hours. After cooling the solution was acidified with hydrochloric acid then extracted two times with 200 ml of CH2 Cl2. The extracts were dried on sodium sulfate and evaporated to leave 35 g (Yield=78%) of 3,3-dimethoxy-propanoic acid as an oil.

	With lithium hydroxide;	C) (S)-4-Benzyloxy-2-[[2-(3,4-dichloro-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric Acid methyl ester; A solution of 1.26 g (2.96 mmol) of (S)-4-benzyloxy-2-[2-(3,4-dichloro-phenylamino)-propylamino]-butyric acid methyl ester in 30 ml CH2Cl2 was treated with a solution of 0.91 g (3.55 mmol) of 2-chloro-1-methylpyridinium iodide and 0.48 g (3.55 mmol) of 3,3-dimethoxy-propionic acid (synthesized from methyl 3,3-dimethoxy-propionate by hydrolysis with LiOH) in 20 ml of CH2Cl2. The suspension was cooled and treated at 0 C. with 1.77 ml (7.41 mmol) of tributylamine. The cooling bath was removed after 10 min and stirring was continued over night. The reaction was extracted with 10% aq. KHSO4 solution/diethyl ether (3×). The organic phases were washed with 10% aq. KHSO4 solution (2×), sat. aq. NaHCO3 solution, 10% aq. NaCl solution and dried over Na2SO4 to yield 1.53 g (96%) of the title compound as a 71:29 mixture of the (R) and (S) diastereomers. Yellow oil, MS: 541.2 (MH+, 2Cl).
		(Cap 5.1 ) (Cap 5.2) Cap 5, step aA mixture of methyl 3,3-dimethoxypropanoate (10 g, 68 mmol) and LiOH (8.08 g, 337 mmol) in MeOH (40 mL), THF (40 mL) and water (40 mL) was heated at 80 C for 2 hours. The mixture was then cooled down to room temperature and acidified with 1 N HC1 aqueous solution (pH>3). The mixture was then extracted with CH2CI2 (3X). The combined organic layers were dried with MgS04 and concentrated to give Cap 5, step a as a clear oil (6.3 g). The product was used in the next reaction without further purification. XH NMR (500 MHz, CDC13) delta 4.82 (t, J=5.8 Hz, 1H), 3.36 (s, 6H), 2.69 (d, J=5.8 Hz, 2H); 13C NMR (125 MHz, CDC13) delta 175.22, 101.09, 53.68, 38.76.
6.3 g	With water; lithium hydroxide; In tetrahydrofuran; methanol; at 80℃; for 2h;	A mixture of methyl 3,3-dimethoxypropanoate (10 g, 68 mmol) and LiOH (8.08 g, 337 mmol) in MeOH (40 mL), THF (40 mL) and water (40 mL) was heated at 80 C for 2 h. The mixture was then cooled down to room temperature and acidified with 1 N HCl aqueous solution (pH>3). The mixture was then extracted with CH2Cl2 (3X). The combined organic layers were dried with MgSO4 and concentrated to give Cap 5, step a as a clear oil (6.3 g). The product was used in the next reaction without further purification. 1H NMR (500 MHz, CDCl3) delta 4.82 (t, J=5.8 Hz, 1H), 3.36 (s, 6H), 2.69 (d, J=5.8 Hz, 2H); 13C NMR (125 MHz, CDCl3) delta 175.22, 101.09, 53.68, 38.76.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3281 - 3286
[2]Journal of Natural Products,2012,vol. 75,p. 181 - 188
[3]Journal of Organic Chemistry,2017,vol. 82,p. 10376 - 10387
[4]Patent: WO2009/76404,2009,A1 .Location in patent: Page/Page column 65-66
[5]Organic Letters,2015,vol. 17,p. 1553 - 1556
[6]Patent: US2007/21408,2007,A1 .Location in patent: Page/Page column 58; 81; 82; 83; 84-85; 86; 88; 89; 91; 94; 95; 97
[7]Patent: US5082847,1992,A
[8]Tetrahedron,1987,vol. 43,p. 143 - 148
[9]European Journal of Organic Chemistry,2001,p. 2041 - 2053
[10]Journal of Organic Chemistry USSR (English Translation),1966,vol. 2,p. 63 - 69
Zhurnal Organicheskoi Khimii,1966,vol. 2,p. 66 - 73
[11]Patent: US2010/22518,2010,A1 .Location in patent: Page/Page column 48
[12]Chirality,2010,vol. 22,p. 534 - 541
[13]Patent: WO2012/154777,2012,A1 .Location in patent: Page/Page column 49
[14]Patent: WO2014/65791,2014,A1 .Location in patent: Page/Page column 49

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[ 34846-90-7 ]
[ 124-41-4 ]
[ 7424-91-1 ]

Reference： [1]Journal of the American Chemical Society,1973,vol. 95,p. 8741 - 8749

4
[ 67-56-1 ]
[ 1116-86-5 ]
[ 7424-91-1 ]
[ 2517-44-4 ]
[ 89-91-8 ]

Reference： [1]Monatshefte fur Chemie,1990,vol. 121,p. 203 - 207
[2]Monatshefte fur Chemie,1990,vol. 121,p. 203 - 207

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[ 67-56-1 ]
[ 41527-39-3 ]
[ 553-90-2 ]
[ 7424-91-1 ]
[ 89-91-8 ]
[ 108-59-8 ]

Reference： [1]Monatshefte fur Chemie,1990,vol. 121,p. 203 - 207
[2]Monatshefte fur Chemie,1990,vol. 121,p. 203 - 207

6
[ 7424-91-1 ]
[ 625-52-5 ]
[ 6490-42-2 ]

Reference： [1]Synthesis,1986,p. 1041 - 1044

7
[ 7424-91-1 ]
[ 691-60-1 ]
[ 25818-96-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride 1.) dioxane, 50 deg C, 2.) reflux; Yield given. Multistep reaction;

Reference： [1]Winckelmann, Ib; Larsen, Erik H. [Synthesis, 1986, # 12, p. 1041 - 1044]

8
[ 7424-91-1 ]
[ 592-31-4 ]
[ 705-06-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride 1.) dioxane, 50 deg C, 2.) reflux; Yield given. Multistep reaction;

Reference： [1]Winckelmann, Ib; Larsen, Erik H. [Synthesis, 1986, # 12, p. 1041 - 1044]

9
[ 7424-91-1 ]
[ 4947-89-1 ]
[ 109773-15-1 ]

Reference： [1]Synthesis,1986,p. 1041 - 1044

10
[ 67-56-1 ]
[ 292638-85-8 ]
[ 7424-91-1 ]

Yield	Reaction Conditions	Operation in experiment
	With cobalt(II) oxide; indium(III) oxide; at 50℃; for 16h;Inert atmosphere;	Raw material composition of this embodiment: methyl acrylate 560g, methanol 716g, cobalt oxide 2.24g, indium oxide 8.96g, concentrated sulfuric acid 17.6g;Preparation Process: Methyl acrylate, methanol and synthetic catalyst were added to the reactor and stirred well to keep the reaction liquid warm to 50C.The reactor was filled with nitrogen and oxygen so that the partial pressures of nitrogen and oxygen were 0.4 MPa and the reaction was started. The reaction time was 16 h.When the content of methyl acrylate in the reaction solution was 3%, the reaction was completed and the etherification reaction product was added.The etherification reaction product is filtered to recover the catalyst, petroleum ether is added to the filtrate, and the mixture is evenly stirred and allowed to stand for stratification.The upper layer is a petroleum ether layer. Atmospheric distillation recovers petroleum ether to give intermediate product methyl 3,3-dimethoxypropionate 703g.From the lower aqueous phase, methanol and methyl acrylate are recovered and applied.Separated methyl 3,3-dimethoxypropionate into the cracking kettle, then slowly added 17.6 g of concentrated sulfuric acid,The temperature was further increased to 190 C., the cleavage reaction was carried out for 20 h, and all lysates were collected to obtain 430 g of crude MAME.The crude MAME was added to the rectification vessel to recover the distillation product by vacuum distillation and weighed to obtain 478 g of the target product methyl 3-methoxyacrylate.The target product obtained in this example was 535 g, and the yield based on methyl acrylate was 82.4%. The product purity was 95.8%.

Reference： [1]Organic Letters,2000,vol. 2,p. 523 - 525
[2]Synthesis,1992,p. 558 - 561
[3]Synthesis,1992,p. 558 - 561
[4]RSC Advances,2016,vol. 6,p. 39387 - 39391
[5]Advanced Synthesis and Catalysis,2004,vol. 346,p. 760 - 766
[6]Tetrahedron,2006,vol. 62,p. 9846 - 9854
[7]Tetrahedron,2008,vol. 64,p. 508 - 514
[8]Patent: CN107879936,2018,A .Location in patent: Paragraph 0016-0020

11
[ 7424-91-1 ]
[ 109-94-4 ]
[ 80370-42-9 ]

Reference： [1]Synthesis,1986,p. 400 - 402

12
[ 7424-91-1 ]
[ 140-38-5 ]
[ 101080-71-1 ]

Reference： [1]Synthesis,1986,p. 1041 - 1044

13
[ 7424-91-1 ]
2-amino-2'-chloro-3,5-dimethylbenzophenone [ No CAS ]
[ 128832-36-0 ]

Yield	Reaction Conditions	Operation in experiment
58.5%	With p-toluenesulfonic acid monohydrate; In benzene;	(1) A mixture of 2-amino-2'-chloro-3,5-dimethylbenzophenone (2.59 g), <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> (3.7 g), p-toluenesulfonic acid hydrate (0.19 g) and benzene (30 ml) was refluxed for 16 hrs., with removal of water by a Dien-Stark apparatus. The mixture was distilled to remove the solvent, and the residue was purified by a column chromatography on silica gel to give methyl 4-(2-chlorophenyl)-6,8-dimethyl-3-quinolinecarboxylate as crystals (1.90 g, 58.5%), which was recrystallized from isopropyl ether as colorless prisms. m.p. 117-118 C. Elemental analysis for C19 H16 ClNO2: Calculated: C, 70.50; H, 4.95; N, 4.30. Found: C, 70.14; H, 4.97; N, 4.27.

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 2079 - 2084
[2]Patent: US5254565,1993,A

14
[ 7424-91-1 ]
[ 3594-90-9 ]
[ 176381-05-8 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sulfuric acid In benzene for 3h; Heating;

Reference： [1]Uno; Ku; Prudent; Huang; Schultz [Journal of the American Chemical Society, 1996, vol. 118, # 16, p. 3811 - 3817]

15
[ 42602-67-5 ]
[ 7424-91-1 ]
(E)-3-(3-Acetylamino-thiophen-2-yl)-acrylic acid methyl ester [ No CAS ]

Reference： [1]Tetrahedron,1998,vol. 54,p. 9055 - 9066

16
[ 17721-06-1 ]
[ 7424-91-1 ]
methyl thieno[3,2-b]pyridine-6-carboxylate [ No CAS ]

Reference： [1]Tetrahedron,1998,vol. 54,p. 9055 - 9066

17
[ 7424-91-1 ]
[ 19228-91-2 ]
[ 212570-86-0 ]

Reference： [1]Tetrahedron,1998,vol. 54,p. 9055 - 9066

18
[ 67-56-1 ]
[ 292638-85-8 ]
[ 7424-91-1 ]
[ 5788-17-0 ]
[ 3852-09-3 ]

Reference： [1]Chemical Communications,1999,p. 985 - 986
[2]Chemical Communications,1999,p. 985 - 986
[3]Chemical Communications,1999,p. 985 - 986
[4]Chemical Communications,1999,p. 985 - 986

19
[ 7424-91-1 ]
[ 107-31-3 ]
sodium (1Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydride; In 1,2-dimethoxyethane; at 0 - 35℃; for 16.5h;	Step A: Sodium (Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate: A 1 L flask was charged with methyl 3,3-dimethoxypropanoate (50.1 g, 328 mmol), 1,2-dimethoxyethane (200 mL) and methyl formate (47.8 g, 787 mmol). The reaction mixture was cooled to 0 C. and NaH (60% suspension in mineral oil, 17.1 g, 426 mmol) was added portionwise. The reaction mixture was stirred at 0 C. for 30 minutes and then heated to 35 C. to initiate reaction. After stirring at ambianet temperature for 16 hours, the reaction mixture was diluted with ether (125 mL), the solids were collected by filtration and washed with ether (50 mL). The white solids were dried in vacuo to give the desired product (58.4 g, 90%).
61%		Step 3a. 2-Chloro-pyrimidine-5-carboxylic acid methyl ester (compound 1001-7) A mixture of NaH (27 g, 60% in mineral oil, 0.675 mol) in anhydrous 1,2-dimethoxyethane (300 mL) was heated to 40-50 C. Methyl 3,3-dimethoxy propionate (100 g, 0.675 mol) was added dropwise. The resulting mixture was stirred for 0.5 h and anhydrous methyl formate (81 g, 1.35 mol) was added dropwise at 40-50 C. The resulting mixture was stirred at 40-50 C. (inner temperature) for 2 h before it was cooled to 0 C. The reaction mixture was allowed to warm to 25 C. slowly and stirred overnight. Et2O (150 mL) was added and stirred for 30 min. The resulting suspension was filtered. The solid was washed with Et2O (100 mL), collected and dried to afford sodium (Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate as an off-white solid (82 g, 61%). LCMS: m/z 130.8 [M+1]+. 1H NMR (400 MHz, CD3OD): delta 3.36 (s, 6H), 3.60 (s, 3H), 5.34 (s, 1H), 8.92 (s, 1H).
61%		Step e: Sodium (Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate (Compound 206) A mixture of NaH (27 g, 60% in mineral oil, 0.675 mol) in anhydrous 1,2-dimethoxyethane (300 mL) was heated to 40-50 C. and methyl 3,3-dimethoxy propionate (205) (100 g, 0.675 mol) was added dropwise. The resulting mixture was stirred for 0.5 h and anhydrous methyl formate (81 g, 1.35 mol) was added dropwise at 40-50 C. The resulting mixture was stirred at 40-50 C. (inner temperature) for 2 h before it was cooled to 0 C. The reaction mixture was allowed to warm to 25 C. slowly and stirred overnight. Et2O (150 mL) was added and stirred for 30 min. The resulting suspension was filtered. The solid was washed with Et2O (100 mL), collected and dried to afford the title compound 206 (82 g, 61%) as an off-white solid. LCMS (m/z): 130.8 [M+1]+. 1HNMR (400 MHz, CD3OD): delta 3.36 (s, 6H), 3.60 (s, 3H), 5.34 (s, 1H), 8.92 (s, 1H).

61%		A mixture of NaH (27 g, 60% in mineral oil, 0.675mo1) in anhydrous 1,2- dimethoxyethane (300 mL) was heated to 40-50 C and methyl 3,3-dimethoxy propionate (205) (100 g, 0.675 mol) was added dropwise. The resulting mixture was stirred for 0.5 hand anhydrous methyl formate (81 g, i.35mo1) was added dropwise at 40-50 C. The resulting mixture was stirred at 40-50 C (inner temperature) for 2 h before it was cooled to 0 C. The reaction mixture was allowed to warm to 25 C slowly and stirred overnight. Et20 (150 mL) was added and stirred for 30 mm. The resulting suspension was filtered. The solid was washed with Et20 (iOOmL), collected and dried to afford the title compound206 (82 g, 61%) as an off-white solid. LCMS (m/z): 130.8 [M+if. ?HNMR (400 MHz, CD3OD): oe 3.36 (s, 6H), 3.60 (s, 3H), 5.34 (s, 1H), 8.92 (s, 1H).
61%		A mixture of NaH (27 g, 60% in mineral oil, 0.675 mol) in anhydrous 1,2-dimethoxyethane (300 mL) was heated to 40-50 C. and methyl 3,3-dimethoxy propionate (205) (100 g, 0.675 mol) was added dropwise. The resulting mixture was stirred for 0.5 h and anhydrous methyl formate (81 g, 1.35 mol) was added dropwise at 40-50 C. The resulting mixture was stirred at 40-50 C. (inner temperature) for 2 h before it was cooled to 0 C. The reaction mixture was allowed to warm to 25 C. slowly and stirred overnight. Et2O (150 mL) was added and stirred for 30 min. The resulting suspension was filtered. The solid was washed with Et2O (100 mL), collected and dried to afford the title compound 206 (82 g, 61%) as an off-white solid. LCMS (m/z): 130.8 [M+1]+. 1HNMR (400 MHz, CD3OD): delta 3.36 (s, 6H), 3.60 (s, 3H), 5.34 (s, 1H), 8.92 (s, 1H).
	With sodium hydride; In 1,2-dimethoxyethane; at 50℃; for 3h;	Step A: To a solution of <strong>[7424-91-1]3,3-dimethoxy-2-methyl propionate</strong> (2.6 g, 17.6 mmol) in DME (12.5 mL) was added methyl formate (5 mL, 81 mmol), followed by NaH (880 mg, 0.02 mmol). The resulting yellow solution was heated to 50C for 3 h before cooling to rt and diluting with Et2O. A white solid precipitate was filtered and dried under vacuum to give sodium (1Z)-2-(dimethoxymethyl)-3-methoxy-3-oxo-1-propen-1-olate, which was used directly in the next step.
	With sodium hydride; In tetrahydrofuran; at 0 - 50℃; for 4h;	Methyl 3,3-dimethoxypropanoate ( 1 00 g, 675 mmol) and methyl formate (8 1 g, 1 350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60% dispersion; 32.4 g, 8 1 0 mmol, 1 .2 eq.) was then added slowly in portions at 0 C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification.
	With sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 50℃; for 4h;	Step 1 . Sodium (Z)-2-(dimethoxymethyl)-3-methoxy-3 -oxoprop- I -en- l -olate. Methyl 3,3 -dimethoxypropanoate ( 1 00 g, 675 mmol) and metliyl formate (8 1 g, 1 350 mmol ) were dissolved in anhydrous THF (450 mL) Sodium hydride (60% dispersion; 32.4 g, 810 mmol, 1 .2 eq.) was then added slowly in portions at 0 "C The reaction mixture was stirred at rt for 1 h, then was heated at 50 "C for 3 h During this period, H2 evolution was observed After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification.
	With sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 50℃; for 4h;	[0174] Step 1. Sodium (Z)-2- (dimethoxymethyl)-3-methoxy-3 -oxoprop- 1-en-i -olate. Methyl 3,3-dimethoxypropanoate (100 g, 675 mmol) and methyl formate (81 g, 1350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60% dispersion; 32.4 g, 810 mmol, 1.2 eq.) was then added slowly in portions at 0 C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification.
	With sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 50℃; for 4h;	0182] Step 1. Sodium (Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-l-en-l-olate. Methyl 3,3-dimethoxypropanoate (100 g, 675 mmol) and methyl formate (81 g, 1350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60% dispersion; 32.4 g, 810 mmol, 1.2 eq.) was then added slowly in portions at 0 C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification

Reference： [1]Patent: US2007/49603,2007,A1 .Location in patent: Page/Page column 81
[2]Patent: US2014/18368,2014,A1 .Location in patent: Paragraph 0177
[3]Patent: US9249156,2016,B2 .Location in patent: Page/Page column 34; 35
[4]Patent: WO2018/85342,2018,A1 .Location in patent: Page/Page column 26; 28
[5]Patent: US2020/78364,2020,A1 .Location in patent: Paragraph 0088; 0093
[6]Synthesis,2002,p. 720 - 722
[7]Patent: EP2102201,2010,B1 .Location in patent: Page/Page column 68
[8]Patent: WO2013/127266,2013,A1 .Location in patent: Page/Page column 130; 131
[9]Patent: WO2013/127269,2013,A1 .Location in patent: Page/Page column 144
[10]Patent: WO2013/130935,2013,A1 .Location in patent: Paragraph 0174
[11]Patent: WO2013/130943,2013,A1 .Location in patent: Paragraph 0182

20
[ 7424-91-1 ]
C₂₂H₃₀O₈ [ No CAS ]
C₂₆H₃₄O₁₀ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2003,vol. 125,p. 7608 - 7612

21
[ 7424-91-1 ]
C₂₅H₄₂O₈ [ No CAS ]
C₂₉H₄₆O₁₀ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2003,vol. 125,p. 7608 - 7612

22
[ 7424-91-1 ]
[ 925-90-6 ]
[ 832142-15-1 ]

Reference： [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 760 - 766
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 3984 - 4003
[3]Angewandte Chemie - International Edition,2017,vol. 56,p. 3590 - 3593
Angew. Chem.,2017,vol. 129,p. 3644 - 3647,4

23
[ 7424-91-1 ]
[ 93957-49-4 ]
methyl trans-3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With water; trichlorophosphate; In acetic acid; at 25℃; for 9h;Product distribution / selectivity;	Example 1 1.01 g of <strong>[93957-49-4]3-(4-fluorophenyl)-1-isopropyl-1H-indole</strong>, 0.92 g of methyl 3,3-dimethoxypropionate, 0.72 mL of 90 wt% aqueous acetic acid (containing 4 mmol of water) and 6 mL of glacial acetic acid were mixed, then, 0.33 g of phosphorus oxychloride was added dropwise into the mixture at an inner temperature of 25C, the added mixture was stirred for 9 hours at the same temperature to cause a reaction. After completion of the reaction, 16 mL of water was added dropwise into the reaction liquid, and the precipitated crystals were filtrated. The crystals were washed with 20 vol% aqueous methanol, then, dried to obtain 1.25 g of methyl trans-3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]acrylate (yellow solid). Yield: 93%. 1H-NMR (d/ppm, CDCl3, 400 MHz) 1.70 (6H, d, J=7 Hz), 3.76 (3H, s), 4.95 (1H, m), 5.96 (1H, d, J=16 Hz), 7.50 (1H, d, J=8 Hz), 7.57 (1H, d, J=8 Hz), 7.08 to 7.40 (6H, m), 7.82 (1H, d, J=16 Hz)

Reference： [1]Patent: EP1666440,2006,A1 .Location in patent: Page/Page column 9
[2]Tetrahedron Letters,2005,vol. 46,p. 3875 - 3878

24
[ 67-56-1 ]
[ 292638-85-8 ]
[ 7424-91-1 ]
[ 34846-90-7 ]

Reference： [1]Tetrahedron,2006,vol. 62,p. 9846 - 9854

25
[ 7424-91-1 ]
[ 956235-04-4 ]

Yield	Reaction Conditions	Operation in experiment
22%		To a suspension of 2.40 g (7.66 mmol) of Intermediate 28 in 48 ml of dioxane, 0.46 g (11.50 mmol) of NaH (60% dispersion in mineral oil) were added in several portions. The reaction mixture was stirred at 6O0C for 1.5 hours (until not H2 formation was observed). After this time, the mixture was cooled to room temperature and 1.63 ml (1.7O g, 11.50 mmol) of methyl 3,3-dimethoxypropanoate were added. The mixture was stirred at reflux temperature, under N2 atmosphere, for 1.5 hours and then was cooled to room <n="50"/>temperature, 76.8 ml of acetic acid (40% aqueous solution) were added and the stirring continued for 1.5 hours. The crude reaction was treated with water and extracted with dichloromethane (x3). The organic extracts were combined, washed with water, 4% solution of NaHCO3, water, dried (MgSO4) and concentrated. The obtained residue was purified by column chromatography on silica gel performing a gradient elution using mixtures of chloroform/methanol (75:1 -> 25:1) as eluents. Appropriate fractions were combined and concentrated. The title compound was obtained as an oil (607 mg, 22%).

Reference： [1]Patent: WO2007/124898,2007,A1 .Location in patent: Page/Page column 48-49

26
[ 7424-91-1 ]
[ 123-38-6 ]
[ 35351-35-0 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 8820 - 8823

27
[ 67-56-1 ]
[ 292638-85-8 ]
[ 7424-91-1 ]
[ 5788-17-0 ]

Reference： [1]Tetrahedron,2008,vol. 64,p. 508 - 514

28
[ 67-56-1 ]
[ 292638-85-8 ]
[ 7424-91-1 ]
[ 2672-58-4 ]

Yield	Reaction Conditions	Operation in experiment
1: 72.1 % Chromat. 2: 21.6 % Chromat.	With carbon dioxide; oxygen at 80℃; for 15h;
1: 69.3 % Chromat. 2: 10.0 % Chromat.	With carbon dioxide; oxygen at 120℃; for 32h;

Reference： [1]Jiang, Huan-Feng; Shen, Yan-Xia; Wang, Zhao-Yang [Tetrahedron, 2008, vol. 64, # 3, p. 508 - 514]
[2]Jiang, Huan-Feng; Shen, Yan-Xia; Wang, Zhao-Yang [Tetrahedron, 2008, vol. 64, # 3, p. 508 - 514]

29
[ 817641-86-4 ]
[ 7424-91-1 ]
1-tert-Butyl-3-cyclobutyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With acetic acid; at 110℃; for 24h;	To 2-tert-butyl-5-cyclobutyl-2H-pyrazol-3-ylamine (5.0 g, 25.9 mmol) in acetic acid (25 mL) was added methyl dimethoxypropionate (7.4 mL, 51.8 mmol), and then the reaction was heated to 110 C. After 24 hr, the reaction mixture was cooled to room temperature, and concentrated to a viscous oil that was diluted with EtOAc. The organic layer was washed with aqueous NaHCO3 and then the organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of this material was accomplished by MPLC using a 45L Biotage column eluding with 20% EtOAc/hexanes. The product-containing fractions were collected and concentrated under reduced pressure, and the resulting solid was washed with hexanes and dried to afford the title compound (2.0 g, 32% yield) as a colorless solid. Rf=0.33 (10% MeOH/CH2Cl2). 400 MHz 1H NMR (CDCl3) d 7.72 (d, J=9.1 Hz, 1H), 6.26 (d, J=9.1 Hz, 1H), 3.68 (dddd, J=8.7, 8.7, 8.7, 8.7 Hz, 1H), 2.46-2.32 (m, 4H), 2.14-1.89 (m, 2H), 1.71 (s, 9H). LRMS m/z (APCI+) 246 (M+1).
32%	In acetic acid; at 110℃; for 24h;	To 2-TERT-BUTYL-5-CYCLOBUTYL-2H-PYRAZOL-3-YLAMINE (5. 0 g, 25.9 MMOL) in ACOH (25 mL) was added methyl dimethoxypropionate (7.4 mL, 51.8 mmol), and then the reaction was heated to 110 oC. After 24 hr, the reaction mixture was cooled to room temperature, and concentrated to a viscous oil that was treated with EtOAc. The organic layer was washed with aqueous NAHCO3 dried over MGS04, filtered, and concentrated under reduced pressure. Purification of this material was accomplished by MPLC using a 45L BIOTAGE column eluting with 20% EtOAc/hexanes. The product-containing fractions were collected and concentrated under reduced pressure, and the resulting solid was washed with hexanes and dried to afford the title compound (2.0 g, 32% yield) as a colorless SOLID. RF= 0.33 (10% MEOH/CH2CI2) ; 500 MHZ H NMR (CDCI3) d 7.72 (d, J = 9.1 Hz, 1H), 6.26 (d, J = 9.1 Hz, 1H), 3.68 (dddd, J = 8. 7,8. 7,8. 7,8. 7 Hz, 1H), 2.46-2. 32 (m, 4H), 2.14-1. 89 (m, 2H), 1.71 (s, 9H); LRMS m/z (APCI+) 246 (M+1).

Reference： [1]Patent: US2004/266815,2004,A1 .Location in patent: Page 18-19
[2]Patent: WO2005/303,2005,A1 .Location in patent: Page 24

30
[ 7424-91-1 ]
[ 19501-58-7 ]
[ 172595-68-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	With acetic acid; at 70℃; for 4.5h;	(Intermediate Example 38) 5-Methoxy-1-methyl-1H-indole-3-carboxylic acid 4-Methoxyphenylhydrazine hydrochloride (200 mg) and methyl 3,3-dimethoxypropionate (194 mg) were added to acetic acid (8.0 ml) and stirred for 4.5 hours at 70C. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (eluding solvent; ethyl acetate: n-hexane 1: 5 ? 1: 3) to give methyl 5-methoxy-1H-indole-3-carboxylate (259 mg, Y.: 97%). 1H NMR; (DMSO-d6) delta (ppm): 3.8 (3H, s), 3.9 (3H, s), 6.8 (1H, dd), 7.4 (1H, d), 7.5 (1H, d), 8.0 (1H, s), 11.8 (1H, brs). ESI/MS (m/z): 204 (M-H)-.

Reference： [1]Patent: EP1595866,2005,A1 .Location in patent: Page/Page column 18

31
[ 7424-91-1 ]
[ 107-31-3 ]
3,3-dimethoxy-2-methoxycarbonyl-1-propen-1-ol sodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydride; In 1,2-dimethoxyethane; mineral oil; at -5 - 50℃; for 17h;	[0184] To a stuffed solution of compound I (50 g; 337 mmol; 1 eq) in 1,2-dimethoxy ethane (0.2 L) was added methyl fomate (50 mL; 809 mmol; 2.4 eq) and the mixture was cooled to -5 C. To the mixture was added sodium hydride (60% in mineral oil, 17.5 g; 438 mmol; 1.3 eq) in portions and the resulting mixture was stirred at 50 C until effervescence had ceased. The mixture was then allowed to stir at 23 C for 17 h. The mixture was filtered and the solid residue was collected, washed with ether and dried under reduced pressure to afford the title compound (63 g, 100%) as an off-white solid. 1H NMR (CD3OD) oe 8.88 (s, 1H), 8.54 (s, 1H), 5.30 (s, 1H), 3.51 (s, 3H), 3.30 (s, 6H).
83%	With sodium hydride; In 1,2-dimethoxyethane; mineral oil; at 20 - 45℃;Inert atmosphere; Cooling with ice;	Step 1 : Preparation of C71. To an oven-dried flask equipped with a refluxing condenser under nitrogen was added C69 (2.5 ml_, 17 mmol), 1 ,2-dimethoxyethane (12.5 ml_), C70 (2.7 ml_, 43 mmol) and sodium hydride (60% in mineral oil, 0.86 g, 22 mmol). The resulting reaction mixture was heated to 43 C, which took 10 minutes, and maintained at 43 to 45 C for an additional 5 minutes before cooling in an ice-bath. The ice bath was then removed and the mixture was allowed to come to room temperature and stirred for 20.5 hours. Diethyl ether (20 ml.) was added and the solid was collected by filtration to afford C71 as an off-white solid. Yield: 2.8 g, 14 mmol, 83%. 1H NMR (500 MHz, DMSO-de) delta 9.03 (s, 1 H), 5.10 (s, 1 H), 3.38 (s, 3H), 3.13 (s, 6H).
73%	With sodium hydride; In 1,2-dimethoxyethane; at 0 - 50℃; for 20h;	Step 10a: Sodium 3,3-dimethoxy-2-methoxycarbonylprop-1-en-1-oxide (Compound 0302) A 500 mL, three neck, round bottom flask equipped with magnetic stirrer and a reflux condenser is purged with nitrogen. The flask is then charged sequentially with <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> (0301) (26.1 g, 176 mmol), anhydrous 1,2-dimethoxyethane (125 mL), anhydrous methyl formate (25 mL, 400 mmol), 60% NaH (8.5 g, 212.5 mmol), and the mixture was heated to 40-50 C. until evolution of hydrogen gas is observed. The reaction mixture was cooled in an ice bath and slowly warmed to room temperature and stirred for 20 h. The reaction mixture was filtered, washed with anhydrous ether, dried to provide desired product 0302 (25.4 g, 73%) as a white power.

50%	With sodium hydride; In 1,2-dimethoxyethane; at 20 - 50℃;	Example 64; (R,S)-3-(4-{1-[2-(4-Trifluoromethyl-phenyl)-pyrimidin-5-yl]-heptyloxy}- benzoylamino) -propionic acid; Step A. Sodium 3,3-dimethoxy-2-methoxycarbonylprop-l-en-l-oxide; A 250 mL, three neck, round bottom flask equipped with magnetic stirrer and a reflux condenser is purged with nitrogen. The flask is then charged sequentially with methyl 3,3-dimethoxyproprionate (5.22 g, 35.3 mmol), anhydrous 1,2-dimethoxyethane (25 mL), anhydrous methyl formate (5 mL), 60% NaH (1.70 g, 42.5 mmol), and the mixture is warmed to 40-50C until evolution of hydrogen gas is observed. The reaction mixture is immediately cooled in an ice water bath and slowly allowed to come to room temperature overnight with stirring. Anhydrous diethyl ether (25 mL) is added, and the resulting suspension is filtered under nitrogen, washed with anhydrous diethyl ether (10 mL), and vacuum dried for 2 hours to give 3.51 g (50%) of sodium 3,3-dimethoxy-2- carbomethoxyprop-1-en-1-oxide as a hydroscopic white powder.
50%	With sodium hydride; In 1,2-dimethoxyethane; at 0 - 50℃;	Example 1; 2-Phenyl-pgammarimidine-5-carboxylic acid benzylamide; Step 1; A 250 mL, three-neck, round-bottom flask equipped with a magnetic stirrer and a reflux condenser is purged with N2. The flask is charged sequentially with <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> (5.22 g, 35.3 mmol), anhydrous 1,2-dimethoxyethane (25 mL), anhydrous methyl formate (5 mL), 60% sodium hydride (1.7 g, 42.5 mmol), and the mixture warmed to 40 - 5O0C until evolution of hydrogen gas stops. The reaction mixture is cooled in an ice/water bath and slowly allowed to reach room temperature overnight with stirring. Anhydrous ether (25 mL) is added, and the resulting suspension is filtered under N2, washed with anhydrous ether (10 mL), and vacuum dried for 2 hours to yield sodium salt of 2-dimethoxymethyl-3-hydroxy-acrylicacid methyl ester (3.51 g, 50%) as a powder. 1H NMR (CD3OD): delta 3.33 (s, 6H), 3.60 (s, 3H), 5.31 (s, IH), 8.89 (s, IH). (see: P. Zhichkin, DJ. Fairfax, S.A. Eisenbeis, Synthesis, 2002, 720-722.)
50%	With sodium hydride; In 1,2-dimethoxyethane; at 0 - 50℃;	Step 2: A 250 mL, three-neck, round-bottom flask equipped with a magnetic stirrer and a reflux condenser is purged with N2. The flask is charged sequentially with methyl 3,3- dimethoxypropionate (5.22 g, 35.3 mmol), anhydrous 1 ,2-dimethoxyethane (25 mL), anhydrous methyl formate (5 mL), 60% sodium hydride (1.7 g, 42.5 mmol), and the mixture warmed to 40 - 5O0C until evolution of hydrogen gas stops. The reaction mixture is cooled in an ice/water bath and slowly allowed to reach room temperature overnight with stirring. Anhydrous ether (25 mL) is added, and the resulting suspension is filtered under N2, washed <n="56"/>with anhydrous ether (10 mL), and vacuum dried for 2 hours to yield sodium salt of 2- dimethoxymethyl-3-hydroxy-acrylicacid methyl ester (3.51 g, 50%) as a powder. 1H NMR (CD3OD): delta 3.33 (s, 6H), 3.60 (s, 3H), 5.31 (s, IH), 8.89 (s, IH). (see: P. Zhichkin, D.J. Fairfax, S.A. Eisenbeis, Synthesis, 2002, 720-722.)
	With sodium hydride; In 1,2-dimethoxyethane; at 20 - 50℃; for 18h;	Reference Production Example 18-1 4-methoxycarbonyl-1H-pyrazole 44.45 g of <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> and 45 ml of methyl formate was dissolved to 180 ml of dimethoxyethane. Under nitrogen atmosphere, 12.8 g of 60 % sodium hydride was added to the solution keeping the temperature of the solution at 40 to 50 C during addition. Then the mixture was stirred at room temperature for 18 hours. 180 ml of diethylether was added to the reaction mixture, as a result, a solid was formed. The solid was collected by filteration, followed by washing with 60 ml of diethylether. The obtained solid was dried under reduced pressure for overnight to obtain 49.41 g of methyl 2- (dimethoxymethyl) -3-hydroxy-acrylate sodium salt.
	With sodium hydride; In 1,2-dimethoxyethane; at 20 - 50℃;Cooling with ice; Inert atmosphere;	Step 2. Methyl-2-[bis(methyloxy)methyl]-3-hydroxy-2-propenoate sodium salt To neat methyl 3,3-bis(methyloxy)propanoate (10.44 g, 70.5 mmol) in a 500 mL RB flask under nitrogen was added 1,2-Dimethoxyethane (DME) (50 mL) then methyl formate (10 g, 70.5 mmol) and then NaH (3.38 g, 85 mmol). To initiate the reaction, the mixture was briefly heated to 50 C and then once H2 evolution commenced, was cooled in an ice bath and slowly brought to room temperature. The mixture was stirred at RT overnight. The slurry was then treated with Et2O (40 mL) filtered under nitrogen and the filtrated washed with Et2O (2*20 mL) and dried under a stream of nitrogen. Yield 11.4 g white solid.

Reference： [1]Patent: WO2015/95128,2015,A1 .Location in patent: Paragraph 0182; 0183; 0184
[2]Patent: WO2012/73138,2012,A1 .Location in patent: Page/Page column 70
[3]Patent: US2009/76006,2009,A1 .Location in patent: Page/Page column 30; 39
[4]Patent: WO2005/118542,2005,A1 .Location in patent: Page/Page column 94-95
[5]Patent: WO2007/41634,2007,A1 .Location in patent: Page/Page column 34
[6]Patent: WO2008/121670,2008,A1 .Location in patent: Page/Page column 54-55
[7]Patent: EP1710234,2006,A1 .Location in patent: Page/Page column 56
[8]Patent: US2010/29655,2010,A1 .Location in patent: Page/Page column 92

32
2-(3,5-dichlorophenyl)aminonicotinaldehyde [ No CAS ]
[ 7424-91-1 ]
1-(3,5-Dichlorophenyl)-1,2-dihydro-3-di-methoxymethyl-2-oxo-1,8-naphthyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.7%	With sodium; In tetrahydrofuran; methanol; water;	EXAMPLE 31 1-(3,5-Dichlorophenyl)-1,2-dihydro-3-dimethoxymethyl-2-oxo-1,8-naphthyridine Formula (VIII): X=H, R'=CH3, Y'=O, Z1 =3--Cl, Z2 =5--Cl A solution of 42.7 g of 2-(3,5-dichlorophenyl)aminonicotinaldehyde, prepared in Example 29, in 500 ml of tetrahydrofuran containing 35.6 g of <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong>, and a solution of sodium methylate prepared from 5.5 g of sodium in 100 ml of methanol, are stirred for 24 h at room temperature. The reaction mixture is subsequently concentrated under vacuum, water is then added and the crystals formed are filtered off, washed carefully with water and dried to give 44.25 g of 1-(3,5-dichlorophenyl)-1,2-dihydro-3-dimethoxymethyl-2-oxo-1,8-naphthyridine in the form of white crystals melting at 190 C. Yield 75.7%.

Reference： [1]Patent: US5364860,1994,A

33
4-amino-1,1,1-trifluoro-3-buten-2-one [ No CAS ]
[ 7424-91-1 ]
N-2-methoxycarbonylvinyl 4,4,4-trifluoro-3-oxo-1-butenylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With hydrogenchloride; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide;	(1) Step of condensation reaction 11.18 g (0.076 mol) of <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> and 3.04 g (0.076 mol) of sodium hydride (60% oil suspension) were added to 65 ml of N,N-dimethylformamide, followed by cooling with ice. Then, 10.0 g (0.072 mol) of 4-amino-1,1,1-trifluoro-3-buten-2-one was gradually dropwise added thereto. After completion of the dropwise addition, the reaction solution was reacted with stirring for 2 hours, while returning it to room temperature. Then, the reaction solution was heated to 50 C. and further reacted for one hour. After completion of the reaction, the obtained reaction solution was poured into 300 ml of ice water and then neutralized by an addition of concentrated hydrochloric acid. The precipitate was collected by filtration and washed with cool water to obtain 12.06 g (yield: 75%) of N-2-methoxycarbonylvinyl 4,4,4-trifluoro-3-oxo-1-butenylamine (melting point: 93.0-95.3 C.).

Reference： [1]Patent: US5708175,1998,A

34
[ 911010-88-3 ]
[ 7424-91-1 ]
[ 911010-89-4 ]

Yield	Reaction Conditions	Operation in experiment
47%	With sodium t-butanolate; In tetrahydrofuran; at 20℃;	Preparation of 7-benzyl-4-hydroxy-5,6,7,8-tetrahydro-[1,7]naphthyridine-3-carboxylic acid methyl ester; To a suspension of NaOtBu (4.23 g, 34.57 mM) in THF (50 mL) was added a mixture of ethyl 3-amino-1-benzyl-1,2,5,6-tetrahydropyridine-4-carboxylate (3.0 g, 11.52 mM) and methyl 3,3-dimethoxypropanoate (5.12 g, 34.57 mM) in THF (20 mL) in one portion and the mixture was agitated at ambient temeperature overnight. The mixture was concentrated to half the volume before being quenched with ice-cold water. The homogeneous solution was extracted ethyl ether and the aqueous layer was carefully acidified with HCl until acidic. The precipitate was filtered, washed with water, and dried under vacuum to obtain the title compound as an off-white solid (1.6 g, 47%).
	With potassium tert-butylate; In tetrahydrofuran; at 20℃; for 18h;	Step B: Methyl 7-benzyl-4-hvdroxy-5,6,7,8-tetrahvdro-1,7-naphthyridine-3-carboxylateTo a solution of potassium tert-butoxide (34.9 g, 311 mmol) in tetrahydrofuran (250 mL) at 20 C was added ethyl 5-amino-l-benzyl-l,2,3,6-tetrahydropyridine-4-carboxylate (27.0 g, 104 mmol) and methyl 3,3-dimethoxypropanoate (46.1 g, 311 mmol). The resulting mixture was stirred for 18 h, then diluted with ice water (200 mL) and acidified to pH 5 by addition of aqueous 2M HC1 solution. The resulting mixture was basified to pH 8 by addition of saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (200 mL x 2). The combined organic layers were dried over Na2S04 and concentrated, and the residue was purified by silica gel column chromatography (PE/EtOAc = 1/1) to give the title compound. MS: m/z =299.1 (M + 1).

Reference： [1]Patent: US2006/217448,2006,A1 .Location in patent: Page/Page column 34
[2]Patent: WO2015/148344,2015,A2 .Location in patent: Page/Page column 80; 81

35
[ 7424-91-1 ]
[ 80370-42-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a dry 250ml 3-necked flask, sodium hydride (60percent in oil) (778mg, 32.4mmol) was added in diethyl ether (35ml). A condenser was attached and the flask placed under an atmosphere of argon. The mixture was stirred and cooled to 0 0C. Ethyl formate (22ml, 270mmol) was added dropwise, followed by a solution of methyl 3,3- bis(methyloxy)propanoate (3.83ml, 27.0mmol) in diethyl ether (25ml) added dropwise over 10 minutes. The mixture was stirred at 0 0C for 1.5 hours and then warmed to room temperature overnight. Poured into 100ml of ice-water and extracted with diethyl ether (3 x 50 ml) which was discarded. The aqueous phase was acidified (pH 3) with concentrated HCI (3ml) and extracted with dichloromethane (5 x 50ml), dried, filtered and evaporated. The residue was purified using silica gel chromatography, eluting with a mixture of methanol and dichloromethane (0-25percent) to afford the product (D32); MS (ES+) m/e 143 [M-H]".

Reference： [1]Patent: WO2006/97691,2006,A1 .Location in patent: Page/Page column 32

36
[ 121-30-2 ]
[ 7424-91-1 ]
2H-1,2,4-benzothiadiazine-7-(aminosulfonyl)-6-chloro-3,4-dihydro-1,1-dioxide-3-acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride; In 1,4-dioxane; water; at 40 - 90℃; for 0.5h;	To a mixture of 4-chloro-6-aminobenzene-1,3-disulfonamide (Aldrich, 14.1 g, 49.3 mmol) and <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> (Aldrich, 9 mL, 9.4 g, 63.4 mmol) in anhydrous dioxane (50 mL) at 40 C., was added dropwise concentrated HCl (5 mL). The mixture was then heated at 70-90 C. for 30 minutes. The solvent was evaporated, the solid was washed with water, dissolved in EtOAc and dried over Na2SO4. The residue, after evaporation of the solvent, was recrystallized from EtOAc/hexane to give the title compound in quantitative yield as a white solid: mp 237-238 C.; 1H NMR (400 MHz, d6-DMSO) 6 8.06 (br s, 2H), delta 8.00 (s, 1H), 7.53 (br s, 2H), 7.00 (s, 1H), 5.10-5.17 (m, 1H), 3.69 (s, 3H), 2.90-2.94 (m, 2H); 13C NMR (100 MHz, d6-DMSO) delta 168.9, 146.2, 134.5, 128.6, 125.4, 118.1, 117.2, 62.9, 51.9, 38.2. Mass spectrum (API-TIS) m/z 367 (M-H), 370 (MH+), 387 (MNH4+); Anal. calcd for C10H12ClN3O6S2: C, 32.48; H, 3.27; N, 11.36. Found: C, 32.50; H, 3.09; N, 11.15.

Reference： [1]Patent: US2006/189603,2006,A1 .Location in patent: Page/Page column 55

37
[ 7424-91-1 ]
[ 66-22-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	With hydrogenchloride; In water;	EXAMPLE 6 The procedure of Example 4 was repeated in the same manner as in Example 4 except that the amounts of liquid ammonia and urea were changed to 25 ml and 3.0 g, respectively, whereby 2.2 g of the intermediate was obtained. The yield of the intermediate was 48% (based on <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong>). The NMR spectrum and IR spectrum of the so-obtained intermediate were the same as those of the intermediate obtained in Example 4. Under the same conditions as described in Example 4, 1.5 g of the intermediate was heated under reflux in a mixture comprising 20 ml of water and 2 ml of an aqueous 35% hydrochloric acid solution, whereby 0.40 g of uracil was obtained. The yield was 42% (based on the intermediate).

Reference： [1]Patent: US4440928,1984,A

38
[ 7424-91-1 ]
[ 457658-05-8 ]
[ 671777-27-8 ]

Yield	Reaction Conditions	Operation in experiment
		[N- (3-LODOPHENYL)] urea (2.62 g) in dioxane (20 ml) was treated with sodium hydride [(60%] oil dispersion, 0.6 g) under nitrogen at 20 C. After 1 h methyl dimethoxypropionate (2.22 g) was added and the mixture was strirred for 1 h at 20 [C] and then heated to reflux for 2.5 h. The mixture was cooled to room temperature and then 40% aqueous acetic acid (100 ml) was added. The mixture was stirred overnight and the precipitated solid was collected by filtration. The filtrate was extracted with DCM and combined with the solid obtained above to give the title compound (3 g) LCMS RT=2.46 min

Reference： [1]Patent: WO2004/22547,2004,A1 .Location in patent: Page 38
[2]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 4192 - 4201

39
[ 463-51-4 ]
[ 149-73-5 ]
[ 7424-91-1 ]
[ 79-20-9 ]
[ 34846-90-7 ]

Yield	Reaction Conditions	Operation in experiment
	Montmorillonite K10; at 0℃;Product distribution / selectivity;	Example 1: Preparation of methyl 3,3-dimethoxypropionate Simultaneously, but separately, 150 kg/h (1.413 kmol/h) of trimethyl ortho formate (Fluka), comprising 1.5percent by weight of montmorillonite KlO (Sd-Chemie), and 84 kg/h of ketene (ketene content about 70percent, remainder inert gases, such as N2, CO and CO2, i.e. neat ketene about 59 kg/h, that is about 1.4 kmol/h) were fed into a 620 L jet reactor (see figure 1), which had been inertized and cooled to an internal temperature of 0 0C. Under an atmosphere of nitrogen, the reaction mixture was kept at a temperature of about 0 °C and circulated in the loop via a circulating pump. Corresponding to the amount of starting materials added, and also continuously, a corresponding part of the reaction mixture flowed over into a collecting tank. After filtration, the purity of the filtrate was determined by GC as 80percent methyl 3,3-dimethoxypropionate, 8percent unreacted trimethyl orthoformate, 4percent methyl 3-methoxyprop-2-enoate and 4percent methyl acetate.By virtue of its low boiling point, it was easy to remove trimethyl orthoformate by distillation. The recovered starting material was subsequently re-cycled into the reaction mixture. <n="9"/>The yield of methyl 3,3-dimethoxypropionate was 82percent (based on conversion).

Reference： [1]Patent: WO2009/56293,2009,A1 .Location in patent: Page/Page column 7-8

40
[ 7424-91-1 ]
[ 34846-90-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	methanesulfonic acid; at 160℃; for 6h;Product distribution / selectivity;	Example 2: Preparation of methyl 3-methoxyprop-2-enoate Under an atmosphere of nitrogen, 0.2 g (2 mmol) of methanesulfonic acid (Fluka) was added to 150 g of a filtrate, analogously obtained as described in example 1 (about 85percent, 0.86 mol of methyl 3,3-dimethoxypropionate), in a distillation apparatus with round-bottomed flask. Under constant flow of nitrogen, the mixture was slowly heated to 160 °C, and the methanol formed was directly distilled off. After 6 hours, the heat supply was stopped. The methyl 3-methoxy- prop-2-enoate obtained in this manner was 88percent pure (GC) and was purified by rectification at 10 kPa. The yield was 85 g (85percent) of methyl 3-methoxyprop-2-enoate (Ki0 kpa = 950C) with a purity of 99percent (GC).; Example 6: Preparation of methyl 3-methoxyprop-2-enoate After distillative removal of the unreacted trimethyl ortho formate from example 1, 4.4 t (30 kmol) of the methyl 3,3-dimethoxypropionate thus obtained were reacted under an atmosphere of nitrogen with 6 kg (62 mol) of methanesulfonic acid analogously to example 2. <n="10"/>Rectification at 10 kPa gave 2.4 t (21 kmol, 69percent based on trimethyl orthoformate employed) of methyl 3-methoxyprop-2-enoate (Ki0 kpa = 95 °C) in a purity of 93percent (GC).
82%	With potassium hydrogensulfate; at 150 - 160℃; for 4h;	In a 100 ml three-necked flask, 97 g of BJ02, 5 g of potassium bisulfate and 50 g were addedPolyethylene glycol dimethyl ether, Heated to 150 ~ 160 , 4 hours of stirring insulation, vacuum pump distillation was 46.5gMethyl 3-methoxyacrylate, Yield 82percent, GC normalized content of 98.7percent
	toluene-4-sulfonic acid; In water; at 160℃; for 6h;Product distribution / selectivity;	Example 3: Preparation of methyl 3-methoxyprop-2-enoate The reaction was carried out analogously to example 2 using 5 g (content 99percent, 34 mmol) of pure-distilled methyl 3,3-dimethoxypropionate and 25 mg (0.13 mmol) of/?-toluenesulfonic acid monohydrate (Fluka). The resulting crude product had a content of 91percent (GC) of methyl 3- methoxyprop-2-enoate.

	4-aminobenzene sulfonic acid; at 160℃; for 6h;Product distribution / selectivity;	Example 4: Preparation of methyl 3-methoxyprop-2-enoate The reaction was carried out analogously to example 2 using 5 g (content 99percent, 34 mmol) of pure-distilled methyl 3,3-dimethoxypropionate and 47 mg (0.27 mmol) of sulfanilic acid (Fluka). The resulting crude product had a content of 92percent (GC) of methyl 3-methoxyprop-2- enoate.
	phosphoric acid; at 160℃; for 6h;Product distribution / selectivity;	Example 5: Preparation of methyl 3-methoxyprop-2-enoate The reaction was carried out analogously to example 2 using 5 g (content 99percent, 34 mmol) of pure distilled methyl 3,3-dimethoxypropionate and 31 mg (0.31 mmol) of orthophosphoric acid (Fluka). The resulting crude product had a content of 88percent (GC) of methyl 3-methoxyprop-2- enoate.
535 g	With sulfuric acid; at 190℃; for 20h;	Raw material composition of this embodiment: methyl acrylate 560g, methanol 716g, cobalt oxide 2.24g, indium oxide 8.96g, concentrated sulfuric acid 17.6g;Preparation Process: Methyl acrylate, methanol and synthetic catalyst were added to the reactor and stirred well to keep the reaction liquid warm to 50°C.The reactor was filled with nitrogen and oxygen so that the partial pressures of nitrogen and oxygen were 0.4 MPa and the reaction was started. The reaction time was 16 h.When the content of methyl acrylate in the reaction solution was 3percent, the reaction was completed and the etherification reaction product was added.The etherification reaction product is filtered to recover the catalyst, petroleum ether is added to the filtrate, and the mixture is evenly stirred and allowed to stand for stratification.The upper layer is a petroleum ether layer. Atmospheric distillation recovers petroleum ether to give intermediate product methyl 3,3-dimethoxypropionate 703g.From the lower aqueous phase, methanol and methyl acrylate are recovered and applied.Separated methyl 3,3-dimethoxypropionate into the cracking kettle, then slowly added 17.6 g of concentrated sulfuric acid,The temperature was further increased to 190° C., the cleavage reaction was carried out for 20 h, and all lysates were collected to obtain 430 g of crude MAME.The crude MAME was added to the rectification vessel to recover the distillation product by vacuum distillation and weighed to obtain 478 g of the target product methyl 3-methoxyacrylate.The target product obtained in this example was 535 g, and the yield based on methyl acrylate was 82.4percent. The product purity was 95.8percent.

Reference： [1]Patent: WO2009/56293,2009,A1 .Location in patent: Page/Page column 8-9
[2]Patent: CN105418421,2016,A .Location in patent: Paragraph 0020; 0023
[3]Patent: WO2009/56293,2009,A1 .Location in patent: Page/Page column 8
[4]Patent: WO2009/56293,2009,A1 .Location in patent: Page/Page column 8
[5]Patent: WO2009/56293,2009,A1 .Location in patent: Page/Page column 8
[6]Patent: CN107879936,2018,A .Location in patent: Paragraph 0016-0020

41
[ 67-56-1 ]
[ 34846-90-7 ]
[ 7424-91-1 ]

Reference： [1]Organic Process Research and Development,2009,vol. 13,p. 548 - 554

42
[ 7424-91-1 ]
[ 148625-35-8 ]
[ 1226762-75-9 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 3488 - 3491

43
[ 7424-91-1 ]
[ 92403-95-7 ]

Yield	Reaction Conditions	Operation in experiment
99%		Preparation Example 3-14-13,3-Dimethoxy-propan-1-ol 3,3-dimethoxy-propionic acid methyl ester (5 g, 33.7 mmol) was diluted in diethyl ether (100 mL) and then cooled to 0 C. Lithium aluminum hydride (1.41 g, 37.2 mmol) was slowly added thereto and stirred for 1 hour. Water (1.4 mL), 4 N NaOH aqueous solution (1.4 mL) and water (4.2 mL) were added thereto sequentially and then stirred for 1 hour. The produced solid was filtered and then washed with diethylether several times. The collected filtrate was distilled under reduced pressure to give 4.05 g of title compound (99%).1H NMR (500 MHz, CDCl3); delta 4.54 (1H, t), 3.73 (2H, t), 3.36 (6H, s), 1.87 (2H, m)

Reference： [1]Patent: US2011/166121,2011,A1 .Location in patent: Page/Page column 93
[2]Macromolecules,2019,vol. 52,p. 1785 - 1793

44
[ 7424-91-1 ]
[ 29124-57-0 ]
[ 1220418-77-8 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5836 - 5857

45
[ 7424-91-1 ]
[ 107-31-3 ]
[ 50-01-1 ]
[ 308348-93-8 ]

Yield	Reaction Conditions	Operation in experiment
61%		Methyl 3,3-dimethoxypropanoate ( 1 00 g, 675 mmol) and methyl formate (8 1 g, 1 350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60% dispersion; 32.4 g, 8 1 0 mmol, 1 .2 eq.) was then added slowly in portions at 0 C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification. The crude enolate from step 1 was dissolved in DMF (200 mL), and guanidine hydrochloride (64 g, 670 mmol) was added. The mixture was heated at 1 00 C under Ni for 3 h. After cooling to rt, water was added and the mixture was cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum to give the desired product (63 g, 61 % yield for 2 steps).
61%		Methyl 3,3-dimethoxypropanoate ( 1 00 g, 675 mmol) and methyl formate (8 1 g, 1 350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60% dispersion; 32.4 g, 8 1 0 mmol, 1 .2 eq.) was then added slowly in portions at 0 C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification. The crude enolate from step 1 was dissolved in DMF (200 mL), and guanidine hydrochloride (64 g, 670 mmol) was added. The mixture was heated at 1 00 C under N2 for 3 h. After cooling to rt, water was added and the mixture was cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum to give the desired product (63 g, 61 % yield for 2 steps).

Reference： [1]Patent: WO2013/127267,2013,A1 .Location in patent: Page/Page column 82
[2]Patent: WO2013/127268,2013,A1 .Location in patent: Page/Page column 60

46
methyl crotonate [ No CAS ]
[ 40789-98-8 ]
[ 7424-91-1 ]
[ 14559-13-8 ]

Yield	Reaction Conditions	Operation in experiment
29.8%	Stage #1: methyl crotonate; 3-mercapto-2-butanone With sodium methylate In toluene at 15 - 30℃; Industrial scale; Stage #2: With hydrogenchloride In water; toluene Industrial scale;

Reference： [1]Phillips, Gary; Fevig, Thomas L.; Lau, Patrick H.; Klemm, George H.; Mao, Michael K.; Ma, Chun; Gloeckner, James A.; Clark, Art S. [Organic Process Research and Development, 2002, vol. 6, # 4, p. 357 - 366]

47
[ 7424-91-1 ]
[ 395-81-3 ]
[ 1573997-71-3 ]

Yield	Reaction Conditions	Operation in experiment
51.1%	With tin(ll) chloride; In ethanol; at 90℃; for 4h;	To a solution of 5-fluoro-2-nitrobenzaldehyde (5g, 29.6mmol), methyl3,3-dimethoxy propanoate (10.95 g, 73.9 mmol) in ethanol (100 mL). Tin Chloride (22.43 g, 118 mmol) was slowly added in above solution .The reaction mixture was heated to 90C for 4 h. Reaction progress was monitored by TLC. After completion of reaction ethanol was evaporated under reduced pressure and the resultant residue was basified with saturated sodium bicarbonate. The resulting emulsion was filtered through celite, rinsed well with ethyl acetate. The remaining aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to get desired compound. (3.1 g, 51.1 % yield); m/z-206.76.

Reference： [1]Patent: WO2014/33604,2014,A1 .Location in patent: Page/Page column 50

48
[ 7424-91-1 ]
[ 1426942-52-0 ]
[ 1621887-73-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With hydrogenchloride; In 1,4-dioxane; at 95℃; for 1h;Inert atmosphere;	Step 2 - Synthesis of methyl 2-(1 1-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-5, 6-dihydropyrido[3 ?,2 ?:4, 5/pyrimido[1 , 6-a/indol-6- vl)acetate To a solution of 5 -(5 -amino-6-(4-fluoro- 1 H-indol-2-yl)pyridin-2-yl)-2-(4- fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3 -carboxamide (100 mg,0.17 mmol) and methyl 3,3-dimethoxypropanoate (32 mg, 0.22 mmol) in 1,4- dioxane (2 mL) was added 4.0 M HC1 (46 pi, 0.16 mmol) in 1 ,4-dioxane under N2 protection. The resulting mixture was heated to 95 C and stirred at this temperature for 1 h. The reaction was cooled and added Et3N (300 tl). Preparative TLC gave methyl 2-(1 1-fluoro-2-(2-(4-fluorophenyl)-3- (methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5 -yl)-5,6-dihydropyrido [3 ?,2?:4,5]pyrimido [1,6-a] indol-6-yl)acetate (100 mg, yield: 88%). MS (M+H7:686.
88%	With hydrogenchloride; In 1,4-dioxane; at 95℃; for 1h;Inert atmosphere;	To a solution of 5-(5-amino-6-(4-fluoro-lH-indol-2-yl)pyridin-2-yl)-2-(4- fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (100 mg, 0.17 mmol) and methyl 3,3-dimethoxypropanoate (32 mg, 0.22 mmol) in 1,4- dioxane (2 mL) was added 4.0 M HC1 (46 mu, 0.16 mmol) in 1,4-dioxane under N2 protection. The resulting mixture was heated to 95 C and stirred at this temperature for 1 h. The reaction was cooled and added Et3N (300 mu). Preparative TLC gave methyl 2-(l l-fluoro-2-(2-(4-fluorophenyl)-3- (methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-5,6- dihydropyrido[3',2':4,5]pyrimido[l,6-a]indol-6-yl)acetate (100 mg, yield: 88%). MS (M+H)+: 686.

Reference： [1]Patent: WO2014/123794,2014,A1 .Location in patent: Page/Page column 102
[2]Patent: WO2014/121417,2014,A1 .Location in patent: Page/Page column 104

49
[ 147677-00-7 ]
[ 7424-91-1 ]
methyl 3-[4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-5-yl)anilino]propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With triethylsilane; trifluoroacetic acid; In dichloromethane; at 20℃;Inert atmosphere;	To a solution of intermediate I-99a (500 mg, 1 .53 mmol) and methyl 3,3- dimethoxypropanoate (274 mg,1.85 mmol) in CH2CI2 (16 mL) under nitrogen were TEA (8 mL) and triethylsilane (TES, 534 mg, 4.6 mmol) and the reactionmixture was stirred at room temperature overnight until LC-MS showed the starting material was consumed completely. Then concentrated, the mixture was diluted with H20 and adjusted pH to 7 with aq. NaHCO3, extracted with CH2CI2, the organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated to give intermediate I-145a (620 mg, 98%). ESI-MS(Mi-i): 414.2 calc. for 021 H27N504: 413.2.

Reference： [1]Patent: WO2014/131855,2014,A1 .Location in patent: Page/Page column 126
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 8967 - 9004

50
[ 504-29-0 ]
[ 7424-91-1 ]
(E)-methyl 3-(4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With toluene-4-sulfonic acid; In toluene; at 80℃; for 6h;	General procedure: 2-aminopyridine 1a (47 mg, 0.5 mmol), ethyl 3,3-diethoxypropanoate 2 (285 mg, 1.5 mmol) and p-TsOH (8.6 mg, 10 mol %) were stirred in 2 mL of toluene for 6 h at 80 C. After completion of the reaction (monitored by TLC), the water (10 mL) was added. The aqueous solution was extracted with ethyl acetate (3×8 mL) and the combined extract was dried with anhydrous MgSO4. The solvent was removed and the crude product was separated by column chromatography (eluted with petroleum ether/ethyl acetate = 2:1) to give a pure sample of 3a (Yellow crystal, 100 mg, 82%).

Reference： [1]Synlett,2014,vol. 25,p. 1478 - 1481

51
[ 7424-91-1 ]
[ 107-31-3 ]
guanidine hydrochloride salt [ No CAS ]
[ 3167-50-8 ]

Yield	Reaction Conditions	Operation in experiment
65%		Example 9: Step A10 : Preparation of 2-aminopyrimidine-5-carboxylic acid (9b) 1 kg of methyl 3,3-dimethoxypropanoate was dissolved in 7 L of 1 ,4-dioxane. 1 .58 kg of sodium methoxide solution (30 w% in methanol) were added. The mixture was heated to reflux, and ap. 4.9 kg of distillate were removed. The resulting suspension was cooled to r.t., and 0.5 kg of methyl formate was added. The reaction mixture was stirred overnight, then 0.71 kg of guanidine hydrochloride was added, and the reaction mixture was stirred at r.t. for 2 h. The reaction mixture was then heated to reflux, and stirred for 2 h. 13.5 L of water were added, followed by 0.72 kg of aqueous sodium hydroxide solution (45 w%). The reaction mixture was heated at reflux for additional 0.5 h, and then cooled to 50C. 0.92 kg of aqueous hydrochloric acid (25 w%) were added until pH 6 was reached. Seeding crystals were added, and additional 0.84 kg of aqueous hydrochloric acid (25 w%) were added at 50C until pH 2 was reached. The mixture was cooled to 20C and stirred overnight. The suspension was filtered, the collected solids washed twice with water, then twice with methanol, yielding 0.61 kg (65%).

Reference： [1]Patent: WO2016/71435,2016,A2 .Location in patent: Page/Page column 54-55

52
[ 7424-91-1 ]
[ 107-31-3 ]
[ 50-01-1 ]
[ 3167-50-8 ]

Yield	Reaction Conditions	Operation in experiment
65%		1 kg of methyl 3,3-dimethoxypropanoate was dissolved in 7 L of 1 ,4-dioxane. 1 .58 kg of sodium methoxide solution (30 w% in methanol) were added. The mixture was heated to reflux, and ap. 4.9 kg of distillate were removed. The resulting suspension was cooled to r.t., and 0.5 kg of methyl formate was added. The reaction mixture was stirred overnight, then 0.71 kg of guanidine hydrochloride was added, and the reaction mixture was stirred at r.t. for 2 h. The reaction mixture was then heated to reflux, and stirred for 2 h. 13.5 L of water were added, followed by 0.72 kg of aqueous sodium hydroxide solution (45 w%). The reaction mixture was heated at reflux for additional 0.5 h, and then cooled to 50C. 0.92 kg of aqueous hydrochloric acid (25 w%) were added until pH 6 was reached. Seeding crystals were added, and additional 0.84 kg of aqueous hydrochloric acid (25 w%) were added at 50 until pH 2 was reached. The mixture was cooled to 20 and stirred overnight. The suspension was filtered, the collected solids washed twice with water, then twice with methanol, yielding 0.61 kg (65%).

Reference： [1]Patent: WO2016/71426,2016,A1 .Location in patent: Page/Page column 36; 37

53
[ 7424-91-1 ]
methyl (±)-3-hydroxy-4-phenylbutanoate [ No CAS ]
dimethyl cis-(±)-3,4-dihydro-1H-2-benzopyran-1,3-diacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With boron trifluoride diethyl etherate; In dichloromethane; toluene; at 20℃; for 96h;Inert atmosphere;	Under N2, 8 (486 mg, 2.5 mmol) was dissolved in CH2Cl2(10 mL). Methyl 3,3-dimethoxypropionat (19d, 1.11 g, 7.5 mmol,50% in toluene) was added and the mixture was stirred for 30 minat rt. The solution was cooled to 0 C, BF3Et2O (3.2 mL, 20 mmol)was added and the mixture was stirred at rt for 4 d. 0.5 M HCl(17.5 mL) was added and the mixture was extracted with CH2Cl2(3 12.5 mL). The combined organic layers were dried (Na2SO4),concentrated in vacuo and the residue was purified by fc (4 cm, petroleumether/EtOAc = 4:1, 20 mL, Rf = 0.37). colorless solid, yield582.8 mg (84%), mp. 62.9 C. C15H18O5 (278.3). MS (EI): m/z = 278[M], 205 [M-CH2COOCH3], 145 [M-(CH2COOCH3 + COOCH3 + )]. IR: m[cm1] = 2947, 2879 (CAH), 1743, 1723 (CO), 1159, 1103 (CAO),750 (CAH). 1H NMR (CDCl3): d [ppm] = 2.57 (dd, J = 15.3/5.9 Hz,1H, ArCH2CHCH2CO2CH3), 2.68 (dd, J = 15.1/9.2 Hz, 1H, ArCH2),2.70 (dd, J = 15.3/7.4 Hz, 1H, ArCH2CHCH2CO2CH3), 2.76-2.81 (m,2H, ArCHCH2CO2CH3), 2.94 (dd, J = 15.1/3.7 Hz, 1H, ArCH2), 3.70 (s,3H, CO2CH3), 3.71 (s, 3H, CO2CH3), 4.10-4.18 (m, 1H, ArCH2CH),5.23 (dd, J = 9.1/3.7 Hz, 1H, ArCHO), 7.01-7.21 (m, 4H, arom.). Therelative configuration was determined by NOE spectra.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 4045 - 4055

54
4-methoxy-1,1,1-trichloro-3-buten-2-one [ No CAS ]
[ 67-56-1 ]
[ 7424-91-1 ]

Yield	Reaction Conditions	Operation in experiment
93.5%	With potassium hydride; at 10 - 50℃; for 12h;	1500g of anhydrous methanol and 4g (0.1mol) of potassium hydride were added to the flask, stirred and ice-cooled to 10 C, and 203g(1 mol) of 1,1,1-trichloro-4-methoxy-3-buten-2-one in a flask, and then the temperature was raised to 50 C and the reaction was stirred for 12 hours. Excess methanol was removed under reduced pressure, filtered, and the filtrate was distilled under reduced pressure to give 138.0 g of methyl 3,3-dimethoxypropionate (79-81C, 20 mmHg) as a colorless transparent liquid in a yield of 93.5%. NMR (400 MHz, CDCl3)? (Ppm): 1.18 (s, 6H, J = 6.9, OCH3), 1.25 (s, 1H, J = 6.9,2CO2CH3), 4.13 (q, 2H, J = 6.9, CO2CH3), 4.92 (t, 1H, J = 6,3-H). FAB-MS (m / z): 149 [M + H] +.
81%	With potassium carbonate; at 0 - 30℃; for 12h;	In a 1000 ml three-necked flask, 190 g of BJ01 and 250 g of anhydrous methanol were added and the temperature of the ice-salt bath was lowered to 0C to 10C, 20 g of anhydrous potassium carbonate was added, stirred and heated to 20C to 30C,The reaction was incubated for 12 hours. After the reaction was complete, the temperature was reduced to room temperature, and the solid salt was removed by suction filtration. The filtrate was distilled under reduced pressure and the methanol was distilled off. The oil was distilled under reduced pressure to obtain 113 g of BJ02 in 81% yield.

Reference： [1]Patent: CN107056608,2017,A .Location in patent: Paragraph 0029; 0033; 0037
[2]Patent: CN105418421,2016,A .Location in patent: Paragraph 0019; 0025
[3]Organic Syntheses,1990,vol. 69,p. 238 - 238

55
[ 7424-91-1 ]
(S)-1-(trimethylsilyl)hept-1-en-4-ol [ No CAS ]
methyl 2-((2R,6S)-5,6-dihydro-6-propyl-2H-pyran-2-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With methanesulfonic acid; In dichloromethane; at -5℃; for 1h;Inert atmosphere;	To a solution of (Z)-homoallyl alcohol 4 (1.49 g, 8.0 mmol) and methyl 3,3-dimethoxypropanoate (1.78 g, 12.0 mmol) in DCM (50 mL) at -5 C was added CH3SO3H (0.78 mL, 12.0 mmol) under an argon atmosphere. The mixture was stirred for 1 h and quenched with saturated aq. NaHCO3. The layers were separated, and the aqueous layer was extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column chromatography (hexanes/EtOAc, 20:1 to 5:1) to afford dihydropyran 3 (1.1 g, 70%) as a colorless oil: [alpha]26D = + 1.0 (c = 0.26, CHCl3); 1H NMR (400 MHz, CDCl3) delta: 5.84-5.81 (m, 1H), 5.36 (dd, J = 12.0, 4.0 Hz, 1H), 4.53-4.50 (m, 1H), 3.68 (s, 3H), 3.57-3.51 (m, 1H), 2.56 (dd, J = 16.0, 8.0 Hz, 1H), 2.44 (dd, J = 16.0, 4.0 Hz, 1H), 1.95-1.92 (m, 2H), 1.42-1.37 (m, 4H), 0.90 (t, J = 8.0, 3H). 13C NMR (100 MHz, CDCl3) delta: 171.6, 128.7, 125.9, 73.9, 71.6, 51.6, 40.4, 38.0, 31.0, 18.6, 14.0; IR (KBr) numax 2957, 2927, 2873, 1747, 1462, 1378, 1167, 1082, 736 cm-1; HRMS (ESIMS): calcd for C11H19O3 [M + H]+ 199.1329, found 199.1338.

Reference： [1]Tetrahedron Letters,2017,vol. 58,p. 3588 - 3589

56
[ 7424-91-1 ]
[ 106-47-8 ]
[ 1810-67-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: methyl 3,3-dimethoxypropionate; 4-chloro-aniline With sodium hexamethyldisilazane In tetrahydrofuran; 2-methyltetrahydrofuran at 0 - 22℃; for 16h; Stage #2: With sulfuric acid In dichloromethane at 0 - 22℃; for 0.5h;

Reference： [1]Zaugg, Cornelia; Schmidt, Gunther; Abele, Stefan [Organic Process Research and Development, 2017, vol. 21, # 7, p. 1003 - 1011]

57
[ 7424-91-1 ]
[ 1003-99-2 ]
N-(2-bromo-5-fluorophenyl)-3,3-dimethoxypropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hexamethyldisilazane; In tetrahydrofuran; at 0 - 15℃; for 18h;Inert atmosphere;	To a solution of 2-bromo-5-fluoroaniline (50 g, 263 mmol) and methyl 3,3- dimethoxypropionate, (45 mL, 316 mmol) in THF (150 mL) was added NaHMDS in THF (394 mL, 394 mmol) dropwise at 0C. The mixture was stirred at the temperature for 10 minutes, and then it was warmed up to 15 C and stirred for 18 hrs. The reaction was quenched with sat. aqueous solution of NH4Cl and concentrated to about 300 mL. The solution was diluted with water and extracted with EtOAc. The organic layer was dried over Na2S04 and concentrated to afford compound 90b (100 g, 90% yield). MS: calc'd 306 [(M+H)+], measured 306 [(M+H)+].
	With sodium hexamethyldisilazane; In tetrahydrofuran; at 0 - 15℃; for 18h;	To the solution of 2-bromo-5-fluoroaniline (CAS: 1003-99-2, Vendor: TCI, 50 g, 263.14 mmol) and <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> (CAS: 7424-91-1, Vendor: Accela, 45 mL, 315.77 mmol) in THF (150 mL) was added NaHMDS in THF (1M, 394 mL, 394.72 mmol) dropwise at 0 C. After being stirred at 0 C for 10 mins, the mixture was warmed up to 15 C and stirred for 18 hrs. The reaction was quenched by addition of 100 mL sat. NH4Cl and concentrated to about 300 mL. The solution was diluted with 500 mL water and extracted with 200 mL EA for three times. The combined organic layer was washed with 200 mL water twice and 100 mL brine, dried over Na2S04 and concentrated to give the cmde product LI (100 g) as a brown oil. MS calc?d 32l(MH+), measured 321 (MH+).
	With sodium hexamethyldisilazane; In tetrahydrofuran; at 0 - 15℃; for 18h;	To the solution of 2-bromo-5-fluoroaniline (CAS: 1003-99-2, Vendor: TCI, 50 g, 263.14mmol) and <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> (CAS: 7424-91-1, Vendor: Accela, 45 mL, 315.77mmol) in THF (150 mL) was added NaHMDS in THF (1M, 394 mL, 394.72 mmol) dropwise at0 C. After being stirred at 0 C for 10 mins, the mixture was warmed up to 15 C and stirred for18 hrs. The reaction was quenched by addition of 100 mL sat. NH4C1 and concentrated to about300 mL. The solution was diluted with 500 mL water and extracted with 200 mL EA for three times. The combined organic layer was washed with 200 mL water twice and 100 mL brine, dried over Na2SO4 and concentrated to give the crude product Li (100 g) as a brown oil. MS calc?d 321(MHj, measured 321 (MHj.

Reference： [1]Patent: WO2019/233941,2019,A1 .Location in patent: Page/Page column 132; 133
[2]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011
[3]Patent: WO2019/238616,2019,A1 .Location in patent: Page/Page column 50
[4]Patent: WO2020/64792,2020,A1 .Location in patent: Page/Page column 48

58
[ 7424-91-1 ]
[ 29027-17-6 ]
N-(2-chloro-3-methylphenyl)-3,3-dimethoxypropanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

59
[ 7424-91-1 ]
[ 95-81-8 ]
N-(2-chloro-5-methylphenyl)-3,3-dimethoxypropanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

60
[ 7424-91-1 ]
[ 113206-03-4 ]
N-(2-chloro-3-methoxyphenyl)-3,3-dimethoxypropanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

61
[ 7424-91-1 ]
[ 29242-84-0 ]
N-(2-chloro-4-methoxyphenyl)-3,3-dimethoxypropanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

62
[ 7424-91-1 ]
[ 51114-68-2 ]
N-(3-chloro-2-methoxyphenyl)-3,3-dimethoxypropanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

63
[ 7424-91-1 ]
[ 93-50-5 ]
N-(4-chloro-2-methoxyphenyl)-3,3-dimethoxypropanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

64
[ 7424-91-1 ]
[ 54396-44-0 ]
3,3-dimethoxy-N-(2-methyl-3-(trifluoromethyl)phenyl)propanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

65
[ 7424-91-1 ]
[ 25449-96-1 ]
3,3-dimethoxy-N-(2-methyl-5-(trifluoromethyl)phenyl)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane In tetrahydrofuran; 2-methyltetrahydrofuran at 0 - 22℃; for 16h;

Reference： [1]Zaugg, Cornelia; Schmidt, Gunther; Abele, Stefan [Organic Process Research and Development, 2017, vol. 21, # 7, p. 1003 - 1011]

66
[ 7424-91-1 ]
[ 106877-29-6 ]
3,3-dimethoxy-N-(5-methyl-2-(trifluoromethyl)phenyl)propanamide [ No CAS ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1003 - 1011

67
[ 7424-91-1 ]
C₉H₁₂ClN₃O [ No CAS ]
C₁₄H₂₀ClN₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.8%	With sodium hydride; In tetrahydrofuran; at 0 - 25℃; for 5.5h;	In the reaction bottle,Compound 21g (0.1mol)And 18 g (0.12 mol) of <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> was added to 80 mL of tetrahydrofuran.After mixing uniformly, 50 mL of sodium hydride 6 g (0.15 mol) in THF was added at 0 C,After the addition, the reaction was carried out for 30 min.The temperature was raised to 25 C and the reaction was continued for 5 h.Then, the temperature was lowered to 5 C, 60 mL of an aqueous solution of sodium citrate having a mass percentage of 20% was added, and after stirring for 30 minutes, the organic phase was separated, concentrated, and then 100 mL of dichloromethane was added, and the mixture was washed twice with 50 mL of water.It was dried over anhydrous sodium sulfate and concentrated to give a compound 29 g.The yield is 87.8%.

Reference： [1]Patent: CN108329334,2018,A .Location in patent: Paragraph 0061; 0062; 0063

68
[ 7424-91-1 ]
[ 62-53-3 ]
[ 122347-19-7 ]

Yield	Reaction Conditions	Operation in experiment
75%	With lithium diisopropyl amide; In tetrahydrofuran; at 0 - 25℃; for 5.5h;Green chemistry;	In the reaction flask, 9.3 g (0.1 mol) of aniline and 18 g (0.12 mol) of <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> were added to 80 mL of tetrahydrofuran.After uniformly mixing, a solution of 16 g (0.15 mol) of diisopropylamide lithium in 50 mL of THF was added at 0 C, and the reaction was carried out for 30 min after the dropwise addition, and the temperature was raised to 25 C to continue the reaction for 5 h.Then, the temperature was lowered to 5 C, 60 mL of a 20% aqueous sodium citrate solution was added, and after stirring for 30 minutes, the organic phase was separated.After concentration, 100 mL of dichloromethane was added, and the mixture was washed twice with 50 mL of water, dried over anhydrous sodium sulfate and concentrated to give 15 g.The yield was 75%.

Reference： [1]Patent: CN108440409,2018,A .Location in patent: Paragraph 0043; 0044; 0045; 0046

69
[ 7424-91-1 ]
5-fluoro-2-iodoaniline [ No CAS ]
N-(5-fluoro-2-iodophenyl)-3,3-dimethoxypropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hexamethyldisilazane; In tetrahydrofuran; at 0 - 20℃; for 1.5h;Inert atmosphere;	A solution of N-(5-fluoro-2-iodophenyl)-3,3-dimethoxypropanamide (24 g, 68 mmol) in DCM (20 mL) is added dropwise at RT to sulfuric acid (100 g, 1.02 mol). The RM is stirred at RT for 2h, then concentrated under reduced pressure. The residue is added to 250 g ice, DCM (500 mL) is added and the RM is stirred for 15 min. The organic layer is separated and washed with water then concentrated under reduced pressure, affording the title compound as a beige solid (19 g, 97%). LC-MS A: tR= 0.72 min; [M+H]+= 289.97.

Reference： [1]Patent: WO2018/210992,2018,A1 .Location in patent: Page/Page column 75; 119; 120

70
[ 7424-91-1 ]
C₆H₅BrN₄ [ No CAS ]
C₁₁H₁₃BrN₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.4%	With potassium hydride; In tetrahydrofuran; at 0 - 25℃; for 5.5h;	In the reaction flask, the compound 21 g (0.1 mol) and <strong>[7424-91-1]3,3-dimethoxypropionate methyl ester</strong> 18 g (0.12 mol) was added to 80 mL of tetrahydrofuran, and after mixing uniformly, 50 mL of 6 g (0.15 mol) of THF solution of potassium hydride was added at 0 C, and the reaction was carried out for 30 min after the dropwise addition, and the temperature was raised to 25 C for 5 h, and then the temperature was lowered to 5 C, 60mL of sodium citrate aqueous solution 60mL was added, stirred for 30min, the organic phase was separated, concentrated, then added to 100mL of dichloromethane, washed twice with 50mL of water, dried with anhydrous sodium sulfate and concentrated to give a compound 29g for88.4%;

Reference： [1]Patent: CN108912147,2018,A .Location in patent: Paragraph 0025; 0026; 0027; 0028

71
4-amino-1,1,1-trifluoro-3-buten-2-one [ No CAS ]
[ 7424-91-1 ]
N-(2-methoxycarbonylvinyl)-4,4,4-trifluoro-3-oxo-1-butenamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.06%		1) Add 4.3 kg of sodium methoxide, 50 L of N,N-dimethylformamide and 10 kg of methyl 3-methoxypropionate to the reaction flask at room temperature, stir to stir, and the reaction mixture is suspended, slowly warming to 35 C, about 0.5h, to obtain a reaction solution A3; 2) At this temperature, 11.2 kg of (E)-4-amino-1,1,1-trifluorobut-3-en-2-one was added dropwise, and the reaction solution became dark red, and the temperature was maintained for 2 h after the dropwise addition. After the reaction is completed, the reaction liquid B3 is obtained; 3) Pour the reaction solution B3 into 250 L of ice water, stir for 30 min in an ice water bath, precipitate yellow-green small particles, filter, and dry to obtain Nu,N-bis(4-methoxycarbonyl-2,4-pentadienoic acid methyl ester-5-)azane, yield 60%.

Reference： [1]Patent: CN109111369,2019,A .Location in patent: Paragraph 0019; 0020

72
[ 7424-91-1 ]
benzyl 5-(4-fluorophenyl)-6-isopropylpyrrolo[2,3-f]indazole-1(5H)-carboxylate [ No CAS ]
benzyl 5-(4-fluorophenyl)-6-isopropyl-7-[(E)-3-methoxy-3-oxoprop-1-enyl]pyrrolo[2,3-f]indazole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With methanesulfonic acid; In chloroform; toluene; at 20 - 50℃;	To a solution of benzyl 5-(4-fluorophenyl)-6-isopropyl-pyrrolo[2,3-f]indazole-l- carboxylate (l22g, 282 mmol) dissolved in dichloromethane (1 L) was added methyl 3,3- dimethoxypropanoate (42 mL, 296 mmol) and trifluoroacetic acid (140 mL, 1.8 mol). The reaction was stirred overnight at 50 C. An additional 0.1 equivalents of methyl 3,3- dimethoxypropanoate were then added and the mixture stirred for an additional 6h at 50 C. The reaction mixture was concentrated to an oil, and then diluted with dichloromethane.The mixture was washed with saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the product as yellow oil, which was progressed to the next step without further purification. Yield: 140 g, 81%. LCMS m/z 512.3 [M+H]+.

Reference： [1]Patent: WO2020/81257,2020,A1 .Location in patent: Paragraph 00277; 00318; 00351; 00353; 00598

73
[ 7424-91-1 ]
benzyl 5-(4-fluorophenyl-2,3,5,6-d4)-6-isopropylpyrrolo[2,3-f]indazole-1 (5H)-carboxylate [ No CAS ]
methyl (E)-3-(5-(4-fluorophenyl-2,3,5,6-d4)-6-isopropyl-1,5-dihydropyrrolo[2,3-f]indazol-7-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With trifluoroacetic acid; In dichloromethane; at 37 - 38℃; for 40h;	To benzyl 5-(4-fluorophenyl-2,3,5,6-d4)-6-isopropylpyrrolo[2,3-f]indazole- l(5H)-carboxylate (077) (29.6 g, 68.6 mmol) and <strong>[7424-91-1]methyl 3,3-dimethoxypropionate</strong> (11 ml, 77.6 mmol) in dichloromethane (220 ml) was added TFA (23 ml, 300 mmol). The mixture was heated to 37-38 C for 40 hours, then cooled to room temperature. The mixture was slowly added to sodium bicarbonate (35 g, 417 mmol) in water (380 ml) [gas evolved], rinsing in with dichlorom ethane (30 ml). The layers were mixed well and then separated. The aqueous layer was re-extracted with dichloromethane (60 ml). The combined organic layers were dried over MgS04(10 g), silica (10 g) and magensol 10 g) then filtered through a pad of silica (10 g), washing with dichloromethane (120 ml). The filtrate was evaporated and the residue was taken up in MTBE (60 ml) at 45 C [crystals formed on stirring] n- Heptane (60 ml) was gradually added and the slurry was cooled to 15 C, filtered and washed with 2: 1 heptane :MTBE (60 ml). The solids were dried under vacuum at 40 C to afford methyl (E)-3-(5-(4-fluorophenyl-2,3,5,6-d4)-6-isopropyl-l,5-dihydropyrrolo[2,3- f]indazol-7-yl)acrylate (29.8 g, 57.8 mmol, 84 %) as a yellow-brown solid.

Reference： [1]Patent: WO2020/81257,2020,A1 .Location in patent: Paragraph 00277; 00318; 00528

74
[ 7424-91-1 ]
[ 782-17-2 ]
methyl (E)-3-[2-(4-fluorophenyl)-1H-indol-3-yl]prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With trifluoroacetic acid In dichloromethane at 40℃; for 3h;	2 Step 2. Synthesis of methyl (E)-3-[2-(4-fluorophenyl)-lH-indol-3-yl]prop-2-enoate (C99) 2-(4-fluorophenyl)-lH-indole (1.0 g, 4.76 mmol) and methyl 3,3- dimethoxypropanoate (0.81 mL, 5.7 mmol) were suspended in dichloromethane (15 mL). Trifluoroacetic acid (2.00 mL, 26 mmol) was added rapidly via syringe, resulting in a clear brown solution. The reaction mixture was heated to 40 °C for three hours. The reaction was diluted with dichloromethane (15 mL) to give an amber solution which was washed with saturated aqueous NaHCCh (25 mL) to yield a bright yellow/light amber biphasic mixture. The phases were separated and the organic layer was washed with saturated NaHCCh (30 mL), then dried (MgSCh) and filtered. The mixture was concentrated under a nitrogen stream overnight. The crude product was obtained as a yellow powder. The product was dissolved in minimum 2-MeTHF and pentane added until the suspension became lightly cloudy. The suspension was allowed to stand overnight, and the precipitate was filtered off. The filter cake was washed with heptane (2 x 15 mL), and dried in vacuo at 40 °C to afford the product as a yellow powder. Methyl (E)-3-[2-(4-fluorophenyl)-lH-indol-3-yl]prop-2-enoate (1.30 g, 86 %). NMR (300 MHz, Chloroform -if) d 8.41 (s, 1H), 8.01 - 7.95 (m, 1H), 7.92 (d, J = 16.0 Hz,1H), 7.58 - 7.50 (m, 2H), 7.46 - 7.41 (m, 1H), 7.33 - 7.27 (m, 2H), 7.22 (t, J = 8.6 Hz, 2H), 6.59 (d, J = 16.0 Hz, 1H), 3.79 (s, 3H). LCMS m/z 295.97 [M+H]+.

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - WO2020/131807, 2020, A1 Location in patent: Paragraph 00402

75
[ 7424-91-1 ]
[ 111721-75-6 ]
[ 1001322-86-6 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: methyl 3,3-dimethoxypropionate; 2-bromo-3-fluoroaniline With sodium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 16h; Inert atmosphere; Stage #2: With sulfuric acid In dichloromethane at 0℃; for 0.5h;
	Stage #1: methyl 3,3-dimethoxypropionate; 2-bromo-3-fluoroaniline With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: With sulfuric acid In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	Method i: Quinolone formation General procedure: Under Argon, at 0°C, to a solution of aniline derivative (1.0 eq.) in THF (C = 0.2 M) was added methyl 3,3-dimethoxypropanoate (1.2 eq.) followed by the addition dropwise of LiHMDS (1M in THF, 2.5 eq.). The reaction mixture was stirred overnight allowing the ice bath coming back at rt. The reaction mixture was hydrolyzed at 0°C with aqueous citric acid solution (20 wt.%) then extracted twice with DCM. Combined organic layers were washed with brine, dried over sodium sulfate and concentrated. (0251) To the obtained crude in DCM (C = 0.2 M) at 0°C was added H2S04conc. (15 eq.). The reaction mixture was stirred 2 h at rt. The reaction mixture was poured on an ice-water mixture, then extracted twice with DCM. Combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude was purified by flash chromatography.

Reference： [1]Chen, Anna; Cummings, Jason E.; Duncan, Leonard R.; English, Anthony; Koci, Bryan; Li, Linsen; Lindert, Steffen; Lu, Yanran; Mann, Chelsea A.; Mcelroy, Craig A.; Mitton-Fry, Mark J.; Nolan, Sheri; Okumu, Antony; Papa, Jonathan L.; Ratigan, Steven C.; Roth, Brieanna; Seffernick, Justin T.; Slayden, Richard A.; Vibhute, Sandip; Wozniak, Daniel J.; Yalowich, Jack [Journal of Medicinal Chemistry, 2021, vol. 64, # 20, p. 15214 - 15249]
[2]Current Patent Assignee: DOMAIN THERAPEUTICS SA - WO2021/23813, 2021, A1 Location in patent: Page/Page column 54; 67

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Code	Phrase
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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

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[ 7424-91-1 ] Synthesis Path-Upstream 1~15

[ 7424-91-1 ] Synthesis Path-Downstream 1~75

Pharmaceutical Intermediates of [ 7424-91-1 ]

Romidepsin Related Intermediates

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Aliphatic Chain Hydrocarbons

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Esters

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