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Product Details of [ 5653-40-7 ]

CAS No. :5653-40-7 MDL No. :MFCD00011671
Formula : C9H11NO4 Boiling Point : -
Linear Structure Formula :- InChI Key :HJVAVGOPTDJYOJ-UHFFFAOYSA-N
M.W : 197.19 Pubchem ID :79736
Synonyms :

Calculated chemistry of [ 5653-40-7 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.22
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 50.79
TPSA : 81.78 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.61 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.27
Log Po/w (XLOGP3) : 1.26
Log Po/w (WLOGP) : 0.99
Log Po/w (MLOGP) : -0.61
Log Po/w (SILICOS-IT) : 0.53
Consensus Log Po/w : 0.69

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.98
Solubility : 2.09 mg/ml ; 0.0106 mol/l
Class : Very soluble
Log S (Ali) : -2.58
Solubility : 0.523 mg/ml ; 0.00265 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.67
Solubility : 4.2 mg/ml ; 0.0213 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.7

Safety of [ 5653-40-7 ]

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 [ 5653-40-7 ]

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

  • Upstream synthesis route of [ 5653-40-7 ]
  • Downstream synthetic route of [ 5653-40-7 ]

[ 5653-40-7 ] Synthesis Path-Upstream   1~35

  • 1
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Reference: [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 5, p. 627 - 629
[2] Arzneimittel-Forschung/Drug Research, 2012, vol. 62, # 8, p. 360 - 366
[3] European Journal of Medicinal Chemistry, 2014, vol. 71, p. 1 - 14
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 3, p. 1452 - 1465
  • 2
  • [ 5653-40-7 ]
  • [ 22608-87-3 ]
Reference: [1] Chemistry - A European Journal, 2012, vol. 18, # 18, p. 5530 - 5535
[2] Organic and Biomolecular Chemistry, 2016, vol. 14, # 38, p. 8966 - 8970
  • 3
  • [ 5653-40-7 ]
  • [ 50377-49-6 ]
Reference: [1] Synthesis, 2004, # 3, p. 429 - 435
[2] Patent: WO2018/172250, 2018, A1,
  • 4
  • [ 4998-07-6 ]
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YieldReaction ConditionsOperation in experiment
83%
Stage #1: With hydrogen In water at 50℃;
Stage #2: With hydrogen In water at 50℃;
48.13 g (0.729 mol) of KOH pellets (w=85percent) are dissolved in 250 ml of ice water. 50 g (0.207 mol) methyl-4,5-dimethoxy-2-nitro-benzoate (1) are added to the clear solution and the resulting green suspension is heated to 70° C. During the heating a dark red solution is formed. Once the reaction has ended (monitored by HPLC) the solution is cooled to ambient temperature and adjusted to pH 6.6 with 34.6 g (0.570 mol) glacial acetic acid. The resulting red suspension is hydrogenated with 1 g of 10percent Pd/C at 50° C. and 3.5 bar until the reaction comes to a standstill. Then the hydrogenation solution is filtered off and adjusted to pH 5.1 with 31.82 g (0.525 mol) glacial acetic acid under an inert gas. The light green suspension is stirred for 30 min at RT, then cooled to 5° C. and stirred for another 30 min.The product (2) is filtered off, washed in two batches with a total of 250 ml of ice water and then dried at 55° C. for 12 h in a vacuum drying cupboard.This reaction yielded 35.18 g (0.173 mol, 83percent of theory) of light grey crystals.
83.7% With palladium on activated charcoal; hydrogen In methanol at 45℃; for 2 h; High pressure Compound 3 (10 g, 44.02 mmol), Pd/C (0.5 g) and 200 mL methanol were added to the 500 mLhigh pressure reactor, the air in the reactor was replaced by H2 (0.1 MPa) three times and shut downthe vent valve. The mixture was stirred at 45 C and 0.4 MPa of H2 for 2 h, after the reaction was over, Pd/C was filtered out and the solution was distilled under vacuum as soon as possible. The resultingresidue was filtered and washed to give a yellow solid 7.2 g with a yield of 83.7percent, m.p. 170.4–172.0 °C.
65% With 5%-palladium/activated carbon; ammonium formate In ethanol for 6 h; Reflux A solution of 2-nitro-4,5-dimethoxybenaoic acid (8 g,35.2 mmol) in EtOH (50 mL) was added with ammonium formate(8.8 g, 139.7 mmol) and 5percent Pd-C (0.19 g) and wad heated to refluxfor 6 h. The reaction was cooled to rt and filtered off the solid. Thesolution was concentrated to dryness that was then purified bysilica gel column to give 2-amino-4,5-dimethoxy benzoic acid (5a)as a white solid (6 g, yield 65percent). mp 156-157 °C; 1H NMR (CDCl3,ppm): δ 7.36 (s, 1H), 6.17 (s, 1H), 3.91 (s, 3H), 3.86 (s, 3H).
34.6% With iron; ammonium chloride In ethanol; water at 100℃; for 3 h; Cooling with ice Intermediate 1 (1 g, 4.40 mmol) was dissolved in 20 ml of absolute ethanol at 80 ° C and dissolved in 20 ml.Water and ammonium chloride (0.47 g, 8.80 mmol) were heated to 100 ° C to add reduced iron powder (1 g, 17.86 mmol) in portions.The reaction was completed by TLC reaction for 3 hours. After the completion of the reaction, the mixture was filtered with hot water, and then filtered and evaporated to ethyl acetate. The silica gel column gave 0.3 g of an off-white solid, yield 34.6percent.
11 g With hydrazine hydrate In methanol at 50℃; for 5 h; Inert atmosphere In a 500 mL reaction flask equipped with a stirrer,16 g of 2-nitro-4,5-dimethoxybenzoic acid was added to the solvent150 mL of methanol, then hydrated hydrazine 105 g and Raney nickel 0.4 g,Nitrogen protection reaction system, heated to 50 ° C reaction, reactionAfter 5 h, the TLC monitors the reaction of the starting material completely, filters the reaction solution, and removes the solvent methanol to give 2-amino-4,5-dimethoxybenzoic acid11g.

Reference: [1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 28, p. 5119 - 5135
[2] Chemistry - An Asian Journal, 2017, vol. 12, # 7, p. 785 - 791
[3] Patent: US2008/319194, 2008, A1, . Location in patent: Page/Page column 4
[4] Molecules, 2018, vol. 23, # 1,
[5] RSC Advances, 2016, vol. 6, # 81, p. 77717 - 77734
[6] The Journal of organic chemistry, 2002, vol. 67, # 23, p. 8284 - 8286
[7] European Journal of Medicinal Chemistry, 2018, vol. 147, p. 227 - 237
[8] Patent: CN108484574, 2018, A, . Location in patent: Paragraph 0124; 0125; 0126
[9] Journal of Organic Chemistry, 1939, vol. 4, p. 71,80
[10] Journal of Organic Chemistry, 1939, vol. 4, p. 71,80
[11] Journal of Heterocyclic Chemistry, 1983, vol. 20, # 6, p. 1581 - 1584
[12] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 13, p. 3959 - 3966
[13] Asian Journal of Chemistry, 2016, vol. 28, # 10, p. 2122 - 2130
[14] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1065 - 1070
[15] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 3, p. 1723 - 1728
[16] Patent: CN106632271, 2017, A, . Location in patent: Paragraph 0035; 0036; 0037
  • 5
  • [ 117573-59-8 ]
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Reference: [1] Tetrahedron Letters, 2002, vol. 43, # 37, p. 6629 - 6631
[2] Synthetic Communications, 2008, vol. 38, # 2, p. 186 - 191
  • 6
  • [ 26759-46-6 ]
  • [ 5653-40-7 ]
Reference: [1] Journal of the American Chemical Society, 1919, vol. 41, p. 2147
[2] Journal of Medicinal Chemistry, 1986, vol. 29, # 5, p. 627 - 629
[3] Journal of Organic Chemistry, 2014, vol. 79, # 23, p. 11339 - 11348
  • 7
  • [ 26791-93-5 ]
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Reference: [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 5, p. 627 - 629
[2] Journal of the American Chemical Society, 1919, vol. 41, p. 2147
  • 8
  • [ 93-07-2 ]
  • [ 5653-40-7 ]
Reference: [1] European Journal of Medicinal Chemistry, 2018, vol. 147, p. 227 - 237
[2] Organic and Biomolecular Chemistry, 2018, vol. 16, # 28, p. 5119 - 5135
[3] Patent: CN108484574, 2018, A,
  • 9
  • [ 2150-38-1 ]
  • [ 5653-40-7 ]
Reference: [1] Journal of Medicinal Chemistry, 1986, vol. 29, # 5, p. 627 - 629
  • 10
  • [ 120-14-9 ]
  • [ 5653-40-7 ]
Reference: [1] Molecules, 2018, vol. 23, # 1,
[2] RSC Advances, 2016, vol. 6, # 81, p. 77717 - 77734
  • 11
  • [ 20357-25-9 ]
  • [ 5653-40-7 ]
Reference: [1] Molecules, 2018, vol. 23, # 1,
[2] RSC Advances, 2016, vol. 6, # 81, p. 77717 - 77734
  • 12
  • [ 93-03-8 ]
  • [ 5653-40-7 ]
Reference: [1] Patent: CN106632271, 2017, A,
  • 13
  • [ 1016-58-6 ]
  • [ 5653-40-7 ]
Reference: [1] Patent: CN106632271, 2017, A,
  • 14
  • [ 3473-63-0 ]
  • [ 5653-40-7 ]
  • [ 13794-72-4 ]
YieldReaction ConditionsOperation in experiment
95.7% at 140 - 170℃; Compound 4 (5.0 g, 25.38 mmol) and formamidine acetate (4.0 g, 38.83 mmol) were dissolved in5 mL of DMSO and heated to 140–170 C under stirring. The initial black color went brown and somesolid was formed. The reaction mixture was constantly stirred for 4h and then cooled to 25 C. 50 mLH2O was added to the mixture and the product was obtained by filtration as a light yellow solid 5.0 gwith a yield of 95.7percent, m.p. 295.5–297.0 °C.
89%
Stage #1: Reflux
Stage #2: With ammonium hydroxide In water
A solution of 2-amino-4,5-dimethoxybenzoic acid 1 (2.02 g, 10 mmol) and formamidine acetate (2.10 g, 20 mmol) in 2-methoxyethanol (50 mL) was refluxed overnight. After evaporation of the solvent, the residue was stirred after adding 10percent NH4OH (18 mL). The resulting residue was filtered, washed with water, and dried to give compound 2 as a dark brown solid (1.83 g, 89percent). 1H NMR (300 MHz, DMSO-d6) δ: 12.11 (1H, s, NH), 8.0 (1H, s, -NCH), 7.44 (1H, s, aromatic-H), 7.14 (1H, s, aromatic-H), 3.90 (3H, s, -OCH3), 3.87 (3H, s, -OCH3).
Reference: [1] Molecules, 2018, vol. 23, # 1,
[2] European Journal of Medicinal Chemistry, 2008, vol. 43, # 7, p. 1478 - 1488
[3] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 2, p. 968 - 977
[4] Synthesis, 2004, # 3, p. 429 - 435
[5] Patent: CN104447769, 2016, B, . Location in patent: Paragraph 0048-0049
  • 15
  • [ 6313-33-3 ]
  • [ 5653-40-7 ]
  • [ 13794-72-4 ]
YieldReaction ConditionsOperation in experiment
64%
Stage #1: at 210℃; for 0.25 h; Heating / reflux
Stage #2: With sodium hydroxide In water at 80℃;
A solution of 9.85 g of compound 10 (5 mmol) and 6.8 g of formamidine hydrochloride (85 mmol) was heated under reflux for 15 min at 210° C. After cooling to 80° C., the solution was basified with saturated sodium hydroxide and washed with n-hexane and water to give 6.59 g of compound 11 (yield, 64percent). 1H-NMR (300 MHz, d6-DMSO): δ 7.98 (s, 1H), 7.42 (s, 1H), 7.11 (s, 1H), 3.89 (d, 6H).
64%
Stage #1: at 210℃; for 0.5 h;
Stage #2: With sodium hydroxide In water
Example 1: Preparation of l-((3S)-3-(4-(3-chloro-2,4-difluorophenylamino)- 7-methoxyquinazolin-6-yloxy)pyrrolidin-l-yl)pro-2-pen-l-one; (1-1) 6,7-dimethoxyquinazolin-4(3H)-one; 36.9 g of 4,5-dimethoxyanthranilic acid was mixed with 25.0 g of formamidine hydrochloride, and the mixture was stirred at 210 °C for 30 minutes. After completion of the reaction, the solid thus obtained was cooled to room temperature, stirred with 200 mi (0.33 M) of aqueous sodium hydroxide and filtered under a reduced pressure. The solid thus obtained was washed with water and air-dried to obtain the title compound (24.6 g, 64percent). 1H-NMR (300MHz, DMSO-d6) δ 7.99 (s, IH), 7.44 (s, IH), 7.13 (s, IH),3.90 (5, 3H), 3.87 (5, 3H).
Reference: [1] Journal of Medicinal Chemistry, 1996, vol. 39, # 1, p. 267 - 276
[2] Journal of Medicinal Chemistry, 2005, vol. 48, # 23, p. 7445 - 7456
[3] Patent: US2005/187231, 2005, A1, . Location in patent: Page/Page column 17
[4] Patent: WO2008/150118, 2008, A2, . Location in patent: Page/Page column 20
  • 16
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YieldReaction ConditionsOperation in experiment
89% at 150℃; General procedure: A mixture of 2-aminobenzoic acid (anthranilic acid)or 2-amino-4,5-dimethoxybenzoic acid (20 mmol) and formamide(20 mmol) was heated at 150 C for 10–18 h. To the resulting mixture50 ml water was added, which resulted in precipitation of a lotof solid. The reaction mixture was stirred for another 30–45 minand the resulting precipitate was filtered and washed with water.The product was recrystallized from ethanol to yield white to paleyellow crystals.
86% for 4 h; Reflux 6,7-dimethoxyquinazolin-4(3H)-one (6a) was prepared accordingto a similar procedure of Luth and Lowe [62], with formamidein replace of formamidine acetate. Briefly, a solution of 5a(5 g, 25.4 mmol) in formamide (30 mL) was heated to reflux for 4 h,cooled to rt and poured onto ice-water, extracted with ethyl acetate,washed with brine and dried over Na2SO4, After removal of thesolvent, the residue was purified by silica gel column to give 6,7-dimethoxyquinazolin-4(3H)-one (6a) as a white solid (4.5 g, yield86percent). mp 310-312 °C (reference mp 300 °C [64]).
86% at 130℃; for 4 h; The intermediate 2 (5 g, 25.37 mmol) was dissolved in 30 ml of formamide and heated at 130 ° C for 4 hours. The reaction was completed by TLC. After the reaction was completed, the reaction solution was poured into a large amount of ice water and extracted with ethyl acetate three times with saturated chlorine. The aqueous sodium chloride solution was washed three times, dried over anhydrous sodium sulfate, and the organic solvent was evaporated under reduced pressure to give a white solid.4.5g yield 86percent,
84.7% at 190 - 200℃; for 2 h; A mixture of methyl 2-amino-4,5-dimethoxybenzoic acid 0101 (2.1 g, 10 mmol), ammonium formate (0.63 g, 10 mmol) and formamide (7 ml) was stirred and heated to 190-200 0C for 2 hours. Then the mixture was cooled to room temperature. The precipitate was isolated, washed with water and dried to provide the title compound 0102 as a brown solid (1.8g, 84.7percent): LCMS: m/z 207[M+l]+; 1UNMR(DMSO) δ 3.87 (s, 3H), 3.89 (s, 3H), 7.12 (s, IH), 7.43 (s, IH), 7.97 (s, IH),12.08 (bs, IH).
84.7% at 190 - 200℃; for 2 h; A mixture of methyl 2-amino-4,5-dimethoxybenzoic acid 0101 (2.1 g, 10 mmol), ammonium formate (0.63 g, 10 mmol) and formamide (7 ml) was stirred and heated to 190-200 0C for 2 hours. Then the mixture was cooled to room temperature. The precipitate was isolated, washed with water and dried to provide the title compound 0102 as a brown solid (1.8g, 84.7percent): LCMS: m/z 207[M+l]+; 1U <n="39"/>NMR(DMSO) δ 3.87 (s, 3H), 3.89 (s, 3H), 7.12 (s, IH), 7.43 (s, IH), 7.97 (s, IH),12.08 (bs, IH).
73% at 140℃; General procedure: To a three necked flask, substituted anthranilic acid (1 meq.) was added in excess of formamide (6 meq). The reaction mixture was then heated at 140 °C for 4-6 h. The reaction was monitored with thin layer chromatography and upon completion; ice was added to the reaction mixture. The resultant solid was filtered, washed with water, dissolved in ethyl acetate, dried over MgSO4 and concentrated to obtain the pure desired product. Where product did not precipitate on addition of ice, the reaction mixture was extracted with ethyl acetate, dried over MgSO4 and concentrated to obtain the desired quinazolin-4(3H)-one derivatives 1-9, 11-15, 17-21 and 23-25.The amino derivatives 10, 16 and 22 were prepared using the following general procedure:To a reaction flask, substituted nitroquinazolin-4(3H)-one derivative (0.3 g, 1.56 mmol) was added followed by addition of 6 mL ethyl acetate and SnCl2*2H2O (2.12 g, 9.42 mmol), then reaction mixture was refluxed for 8 h. The reaction mixture was cooled to room temperature and quenched with saturated sodium bicarbonate solution, followed by repeated extraction with ethyl acetate (3 .x. 50 mL). The organic layers were combined, dried over anhydrous MgSO4 and concentrated to obtain the desired amino substituted quinazolin-4(3H)-one derivatives 10, 16 and 22.The substituted anthranilic acid (1 g) was dissolved in excess acetic anhydride (10 mL) and the resulting reaction mixture was stirred at room temperature for 4-7 h. The reaction was monitored for completion using thin layer chromatography. The solvent was evaporated under vacuum and the resultant residue was stirred with ammonia solution for 7 h. Upon completion, the reaction mixture was extracted with ethyl acetate (3 .x. 10 mL), the organic extracts were combined, dried over MgSO4 and evaporated to obtain compounds 26-30, 31a and 32. The 2-methyl-8-nitroquinazolin-4(3H)-one intermediate (31a) was reduced to compound 31 using the same procedure as reported in Scheme 1 for the synthesis of compounds 10, 16 and 22.
48% at 150℃; General procedure: Method A: To an amount of 1 eq. anthranilic acid or 2-amino-4,5-dimethoxybenzoic acid was added 4 eq. formamide and the reaction mixture was heated for 8-10 h at 150 °C. Then, the mixture was cooled to room temperature and diluted with 50 ml water which resulted in the precipitation of solid. The precipitate was filtered and washed with water. 5.2.2
6,7-Dimethoxyquinazolin-4(3H)-one (2)
Synthesized from 2-amino-4,5-dimethoxybenzoic acid (5 mmol, 1 g) and formamide (20 mmol, 0.92 g).
The product was recrystallized from ethanol to yield brown solid (48percent).
1H NMR (500 MHz, DMSO-d6) δ 12.02 (s, 1H), 7.96 (s, 1H), 7.43 (s, 1H), 7.12 (s, 1H), 3.89 (s, 3H), 3.86 (s, 3H).
13C NMR (126 MHz, DMSO-d6) δ 160.13, 154.58, 148.68, 144.99, 143.92, 115.73, 108.15, 105.08, 56.03, 55.81.
40% at 145℃; for 4 h; Preparation 24 6, 7-Dimethoxyquinazolin-4 (3H) -one A mixture of 2-amino-4, 5-dimethoxybenzoic acid (29.6g, 0.15 mol) and formamide (0.6 mol, 24 mL) was stirred vigorously under nitrogen atmosphere. The mixture was then heated to 145 °C for 4 h. After completion the reaction mixture was cooled and water (120 mL) was added. The solid was filtered, washed with cold water (2 x 20 mL) followed by hexane (2 x 20 mL) to give 12. 5g of the desired product in 40percent yield.
18% at 20 - 190℃; for 8 h; a)
A mixture of 4,5-dimethoxyanthranilic acid (19.7g, 100 mmol) and formamide (10ml) was heated at 190 °C for 5 hours.
The mixture was allowed to cool to approximately 80 °C and water (50ml) was added.
The mixture was then allowed to stand at ambient temperature for 3 hours.
Collection of the solid by suction filtration, followed by washing with water (2 x 50 ml) and drying in vacuo, yielded 6,7-dimethoxy-3,4-dihydroquinazolin-4-one (3.65g, 18 percent yield) as a white solid.
1H-NMR (DMSO d6): 12.10 (s, 1H), 7.95 (s, 1H), 7.42 (s, 1H), 7.11 (s, 1H), 3.88 (s, 3H), 3.84 (s, 3H):
MS (-ve ESI): 205 (M-H)-.
18% at 190℃; for 5 h; a)
A mixture of 4,5-dimethoxyanthranilic acid (19.7 g, 100 mmol) and formamide (10 ml) was heated at 190° C. for 5 hours.
The mixture was allowed to cool to approximately 80° C. and water (50 ml) was added.
The mixture was then allowed to stand at ambient temperature for 3 hours.
Collection of the solid by suction filtration, followed by washing with water (2*50 ml) and drying in vacuo, yielded 6,7-dimethoxy-3,4-dihydroquinazolin-4-one (3.65 g, 18percent yield) as a white solid.
1H-NMR (DMSO d6): 12.10 (s, 1H), 7.95 (s, 1H), 7.42 (s, 1H), 7.11 (s, 1H), 3.88 (s, 3H), 3.84 (s, 3H):
MS (-ve ESI): 205 (M-H)-.

Reference: [1] Journal of Medicinal Chemistry, 1983, vol. 26, # 3, p. 420 - 425
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 24, p. 7858 - 7873
[3] European Journal of Medicinal Chemistry, 2018, vol. 147, p. 227 - 237
[4] Patent: CN108484574, 2018, A, . Location in patent: Paragraph 0127; 0128; 0129
[5] Patent: WO2008/33747, 2008, A2, . Location in patent: Page/Page column 107
[6] Patent: WO2008/33748, 2008, A2, . Location in patent: Page/Page column 37-38
[7] European Journal of Medicinal Chemistry, 2012, vol. 50, p. 264 - 273
[8] Tetrahedron Letters, 2002, vol. 43, # 21, p. 3911 - 3913
[9] Tetrahedron, 2003, vol. 59, # 9, p. 1413 - 1419
[10] European Journal of Medicinal Chemistry, 2016, vol. 117, p. 212 - 229
[11] Patent: WO2005/40163, 2005, A1, . Location in patent: Page/Page column 70-71
[12] Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 8, p. 1203 - 1207
[13] Synthesis, 2004, # 3, p. 429 - 435
[14] Patent: EP1218357, 2005, B1, . Location in patent: Page/Page column 14
[15] Patent: US7081461, 2006, B1, . Location in patent: Page/Page column 31
[16] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6373 - 6377
[17] Patent: EP1154774, 2005, B1, . Location in patent: Page/Page column 51
[18] Patent: EP1119567, 2005, B1, . Location in patent: Page/Page column 25
[19] Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 2, p. 215 - 222
[20] Biochemistry, 2017, vol. 56, # 49, p. 6491 - 6502
[21] Chemistry and Biodiversity, 2018, vol. 15, # 6,
[22] Letters in Drug Design and Discovery, 2018, vol. 15, # 7, p. 757 - 765
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  • [ 13794-72-4 ]
YieldReaction ConditionsOperation in experiment
93% With trimethyl orthoformate In methanol at 70℃; for 4 h; Reflux Step 1 ) 6,7-dimethoxyquinazolin-4(3H)-oneA suspension of 2-amino-4,5-dimethoxybenzoic acid (23.40 g), trimethoxymethane (52 mL), ammonium formate (30.00 g) and methanol (400 mL) was heated to 70 °C and refluxed for 4 h. After the reaction mixture was cooled to room temperature, 160 mL of water was added to the reaction. The mixture was filtered to afford the title compound as a yellow solid (22.70 g, 93.00 percent). The compound was characterized by the following spectroscopic data: ? NMR (400 MHz, d6-DMSO) ?: 3.87 (s, 3H), 3.91 (s, 3H), 7.13 (s, 1 H), 7.45 (s, 1 H), 7.98 (s, 1H).
93% With trimethyl orthoformate In methanol at 70℃; for 4 h; A suspension of 2-amino-4,5-dimethoxybenzoic acid (23.40 g), trimethoxymethane (52 mL), ammonium formate (30.00 g) and methanol (400 mL) was heated to 70° C. and refluxed for 4 h. After the reaction mixture was cooled to room temperature, 160 mL of water was added to the reaction. The mixture was filtered to afford the title compound as a yellow solid (22.70 g, 93.00percent). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, d6-DMSO) δ: 3.87 (s, 3H), 3.91 (s, 3H), 7.13 (s, 1H), 7.45 (s, 1H), 7.98 (s, 1H).
Reference: [1] Patent: WO2013/71697, 2013, A1, . Location in patent: Paragraph 00191
[2] Patent: US2014/228361, 2014, A1, . Location in patent: Paragraph 0265-0266
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YieldReaction ConditionsOperation in experiment
18% With formamide In water a)
A mixture of 4,5-dimethoxyanthranilic acid (19.7 g, 100 mmol) and formamide (10 ml) was heated at 190° C. for 5 hours.
The mixture was allowed to cool to approximately 80° C. and water (50 ml) was added.
The mixture was then allowed to stand at ambient temperature for 3 hours.
Collection of the solid by suction filtration, followed by washing with water (2*50 ml) and drying in vacuo, yielded 6,7-dimethoxy-3,4-dihydroquinazolin-4-one (3.65 g, 18percent yield) as a white solid:
1H-NMR (DMSO-d6): 12.10 (s, 1H), 7.95 (s, 1H), 7.42 (s, 1H), 7.11 (s, 1H), 3.88 (s, 3H), 3.84 (s, 3H):
MS (-ve ESI): 205 (M-H)-.
Reference: [1] Patent: US7235559, 2007, B1,
[2] Chemistry of Heterocyclic Compounds, 2002, vol. 38, # 7, p. 817 - 821
[3] Chemistry of Heterocyclic Compounds, 2002, vol. 38, # 7, p. 817 - 821
[4] Patent: US6414148, 2002, B1,
[5] Patent: US6593333, 2003, B1,
[6] Patent: US6184225, 2001, B2,
[7] Patent: US6265411, 2001, B1,
[8] Patent: US6291455, 2001, B1,
  • 19
  • [ 5653-40-7 ]
  • [ 149-73-5 ]
  • [ 13794-72-4 ]
Reference: [1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 46, p. 8113 - 8126
  • 20
  • [ 79-20-9 ]
  • [ 5653-40-7 ]
  • [ 13794-72-4 ]
YieldReaction ConditionsOperation in experiment
20 g Microwave irradiation The compound of 20g GG1, methyl acetate 17g (1.3eq) into 100ml eggplant-shaped flask, uniformly mixed, the microwave reaction 4πη (60percent power). After cooling, 30ml of water was added, the solid was washed, filtered to obtain compound 20g GG2.
Reference: [1] Patent: CN103570738, 2016, B, . Location in patent: Paragraph 0319-0321
  • 21
  • [ 16712-16-6 ]
  • [ 77287-34-4 ]
  • [ 5653-40-7 ]
  • [ 13794-72-4 ]
YieldReaction ConditionsOperation in experiment
17 g for 10 h; Inert atmosphere; Reflux In a 500 mL reaction flask equipped with a stirrer,20 g of 2-amino-4,5-dimethoxybenzoic acid and 9 g of formamide were added(Ethanol and benzene in a volume ratio of 1: 3), then add 10 g of ammonium formate, under nitrogen protection, heated to reflux reaction, reaction 10h, TLC monitoring of raw materials reaction is complete, steam After removing the solvent, 150 mL of saturated brine was added, and the reaction solution was extracted three times with 100 mL of chloroform. The organic phase was combined and the solvent was evaporated to give 6,7-dimethoxyquinazolin-4-one17g.
Reference: [1] Patent: CN106632271, 2017, A, . Location in patent: Paragraph 0038; 0039; 0040
  • 22
  • [ 290-87-9 ]
  • [ 5653-40-7 ]
  • [ 13794-72-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 4, p. 417 - 420
  • 23
  • [ 593-87-3 ]
  • [ 5653-40-7 ]
  • [ 13794-72-4 ]
Reference: [1] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 925 - 930
  • 24
  • [ 501-53-1 ]
  • [ 5653-40-7 ]
  • [ 20197-92-6 ]
YieldReaction ConditionsOperation in experiment
96%
Stage #1: Heating / reflux
Stage #2: With phosphorus tribromide In diethyl ether for 48 h; Heating / reflux
6,7-dimethoxy-2H-3,1-benzoxazine-2,4(1H)-dione, 13a; 2-amino-4,5-dimethoxybenzoic acid (25 g, 0.13 mole) was added to THF (400 ml), then benzyl chloroformate (54 ml, 0.38 mole) was added with very vigorous stirring. The mixture was refluxed overnight, evaporated to dryness and the residue was vacuum evaporated. Ether (425 ml) was poured on the residue, PBr3 (11.88 ml, 0.13 mole) was added and the mixture was refluxed for 48 h. The reaction mixture was filtered and washed with 3.x.150 ml of ether. The residue was taken up in ether and stirred for 1 h, then filtered, washed and dried. The reaction produced 27 g of the above product in the form of a white powder. Yield: 96percent. 1H NMR (DMSO-d6, 200 MHz): d 3.82 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.66 (s, 1H Ar), 7.27 (s, 1H Ar), 11.58 (s, 1H exchangeable NH).
Reference: [1] Patent: US2006/128695, 2006, A1, . Location in patent: Page/Page column 20
  • 25
  • [ 32315-10-9 ]
  • [ 5653-40-7 ]
  • [ 20197-92-6 ]
YieldReaction ConditionsOperation in experiment
86% for 3 h; Heating / reflux 10.0 g (50.7 mmol) 2-Amino-4,5-dimethoxy-benzoic acid were dissolved in 150 ml tetrahydofuran. 6.52 g (22.0 mmol) triphosgene were added and the solution was boiled for 3 h. After equilibration to room temperature the reaction mixture was poured on a water/ice mixture. The residue was filtrated and rinsed with methanol. Yield: 8.7 g=86percent Grey powder
Reference: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 7, p. 2311 - 2319
[2] Patent: WO2008/52742, 2008, A1, . Location in patent: Page/Page column 20; Sheet 3; Sheet 7
[3] Tetrahedron Letters, 2014, vol. 55, # 26, p. 3607 - 3609
  • 26
  • [ 5653-40-7 ]
  • [ 20197-92-6 ]
Reference: [1] Journal of Medicinal Chemistry, 1982, vol. 25, # 6, p. 703 - 708
  • 27
  • [ 75-44-5 ]
  • [ 5653-40-7 ]
  • [ 20197-92-6 ]
Reference: [1] Journal of medicinal chemistry, 1968, vol. 11, # 1, p. 130 - 136
[2] European Journal of Medicinal Chemistry, 1983, vol. 18, # 3, p. 241 - 247
  • 28
  • [ 67-56-1 ]
  • [ 5653-40-7 ]
  • [ 26759-46-6 ]
Reference: [1] Scientia Pharmaceutica, 2003, vol. 71, # 4, p. 331 - 356
[2] Journal of Organic Chemistry, 2013, vol. 78, # 23, p. 12144 - 12153
[3] Journal of Medicinal Chemistry, 2013, vol. 56, # 21, p. 8332 - 8338
  • 29
  • [ 5653-40-7 ]
  • [ 173043-61-3 ]
Reference: [1] Asian Journal of Chemistry, 2014, vol. 26, # 12, p. 3623 - 3625
  • 30
  • [ 5653-40-7 ]
  • [ 153436-54-5 ]
Reference: [1] Journal of Labelled Compounds and Radiopharmaceuticals, 1998, vol. 41, # 7, p. 623 - 629
[2] Journal of Labelled Compounds and Radiopharmaceuticals, 1997, vol. 40, p. 377 - 379
[3] Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 8, p. 1203 - 1207
[4] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 24, p. 7858 - 7873
  • 31
  • [ 5653-40-7 ]
  • [ 179688-53-0 ]
Reference: [1] Patent: WO2013/71697, 2013, A1,
[2] Patent: US2014/228361, 2014, A1,
[3] Patent: CN103570738, 2016, B,
[4] Patent: WO2008/150118, 2008, A2,
  • 32
  • [ 5653-40-7 ]
  • [ 179688-52-9 ]
Reference: [1] Patent: WO2013/71697, 2013, A1,
[2] Patent: US2014/228361, 2014, A1,
[3] Patent: CN103570738, 2016, B,
[4] Patent: WO2008/150118, 2008, A2,
  • 33
  • [ 5653-40-7 ]
  • [ 788136-89-0 ]
Reference: [1] Patent: WO2013/71697, 2013, A1,
[2] Patent: US2014/228361, 2014, A1,
[3] Patent: CN103570738, 2016, B,
  • 34
  • [ 5653-40-7 ]
  • [ 912556-91-3 ]
Reference: [1] Patent: WO2013/71697, 2013, A1,
[2] Patent: US2014/228361, 2014, A1,
  • 35
  • [ 5653-40-7 ]
  • [ 574745-97-4 ]
Reference: [1] Patent: WO2008/150118, 2008, A2,
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