[ CAS No. 88770-19-8 ] {[proInfo.proName]}

Name: 88770-19-8|Methyl 5-bromothiophene-3-carboxylate|97%
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SKU: A179184
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Quality Control of [ 88770-19-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 88770-19-8 ]

SDS Specification

Alternatived Products of [ 88770-19-8 ]

Product Details of [ 88770-19-8 ]

CAS No. :	88770-19-8	MDL No. :	MFCD13386488
Formula :	C₆H₅BrO₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VFWZOBQPAHYSDL-UHFFFAOYSA-N
M.W :	221.07	Pubchem ID :	45873035
Synonyms :

Calculated chemistry of [ 88770-19-8 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.17
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	43.3
TPSA :	54.54 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.89 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.29
Log Po/w (XLOGP3) :	2.48
Log Po/w (WLOGP) :	2.3
Log Po/w (MLOGP) :	1.69
Log Po/w (SILICOS-IT) :	3.04
Consensus Log Po/w :	2.36

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.01
Solubility :	0.216 mg/ml ; 0.000975 mol/l
Class :	Soluble
Log S (Ali) :	-3.27
Solubility :	0.119 mg/ml ; 0.000537 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.6
Solubility :	0.553 mg/ml ; 0.0025 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.57

Safety of [ 88770-19-8 ]

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

Application In Synthesis of [ 88770-19-8 ]

* 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 [ 88770-19-8 ]
Downstream synthetic route of [ 88770-19-8 ]

[ 88770-19-8 ] Synthesis Path-Upstream 1~6

1
[ 89280-91-1 ]
[ 76360-43-5 ]
[ 88770-19-8 ]

Reference： [1] Journal of Materials Chemistry, 1999, vol. 9, # 9, p. 2155 - 2163

2
[ 67-56-1 ]
[ 100523-84-0 ]
[ 88770-19-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: for 12 h; Reflux Stage #2: With sodium hydrogencarbonate In water	A solution of bromine (2 mL, 39.06 mmol) in glacial acetic acid (64 mL) was added slowly to a stirred solution of Int-1 (5 g, 39.06 mmol) in glacial acetic acid (37 mL) at 0° C. and stirred at room temperature for 20 minutes. The reaction mixture was then poured into ice water while stirring vigorously. The white precipitated solid was filtered, washed with water and recrystallised from hot water to afford pure Int-2 as white solid (3.68 g, 46percent). ¹H NMR (200 MHz, dmso-d₆): δ 7.55 (s, 1H), 8.17 (s, 1H). To a stirred solution of Int-2 (3.4 g, 16.42 mmol) in methanol (40 mL) was added H₂SO₄(321 mg, 3.28 mmol) and stirred under reflux for 12 hours. Volatiles from the reaction mixture were distilled off under reduced pressure and the resulting residue was extracted with DCM (75 mL). The organic extract was washed with water (40 mL), saturated aqueous NaHCO₃solution (40 mL), brine (40 mL) and dried over Na₂SO₄, filtered and concentrated under vacuum to afford pure Int-3 as colorless viscous oil (3.3 g, 91percent). ¹H NMR (200 MHz, dmso-d₆): δ 7.98 (s, 1H), 7.44 (s, 1H), 3.87 (s, 3H). To a stirred solution of Int-3 (0.5 g, 2.26 mmol) in dioxane (25 mL) was added Int-4 (0.51 g, 2.26 mmol) followed by Pd (OAc) 2 (105 mg, 0.45 mmol), xanthpos (265 mg, 0.497 mmol) and CS₂CO₃(1.18 g, 3.62 mmol). The reaction mixture was degassed under vacuum, bubbled with N₂for 10 minutes and stirred under reflux for 20 hours. The reaction mixture was concentrated under reduced pressure and was purified by column chromatography to isolate product and a very close spot together eluting with EtOAc. This mixture (140 mg) was further purified with preparative HPLC to obtain pure Int-5 as a yellow solid (80 mg, 10percent). Mass (m/z): 366.0 [M⁺+1]. ¹H NMR (200 MHz, dmso-d₆): 9.50 (d, J=7 Hz, 1H), 8.51 (d, J=7 Hz, 1H), 8.56 (d, J=5.2 Hz, 1H), 7.74 (brs, 1H), 7.66 (d, J=11.8 Hz, 1H), 7.35 (d, J=7.4 Hz, 1H), 7.11 (s, 1H), 7.02 (d, J=5.6 Hz, 1H), 6.87 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 2.73 (s, 3H). To a stirred solution of Int-5 (0.7 g, 1.91 mmol) in THF: MeOH: H₂O (2:1:2) (50 ml) was added LiOH (0.24 g, 5.74 mmol) at room temperature and stirred while heating at 50° C. for 16 hours. Volatiles from the reaction mixture were distilled off under reduced pressure, the reaction mixture was acidified to about pH 5-6 with 2N HCl. The precipitated solid was filtered and dried under vacuum to afford pure Int-6 (0.51 g, 76percent). Mass (m/z): 352.0 [M⁺+1]. ¹H NMR (200 MHz, dmso-d₆): δ 12.45 (brs, 1H), 10.87 (s, 1H), 9.70 ((brs, 1H), 8.60 (d, J=4.68 Hz, 1H), 7.67-7.59 (m, 2H), 7.45 (t, J=8.4 Hz, 1H), 7.13 (d, J=5.2 Hz, 1H), 7.04 (s, 2H), 2.65 (s, 3H).

Reference： [1] Patent: US2010/29638, 2010, A1, . Location in patent: Page/Page column 110
[2] Tetrahedron Letters, 2013, vol. 54, # 11, p. 1460 - 1462
[3] Journal of Materials Chemistry C, 2018, vol. 6, # 14, p. 3731 - 3742
[4] Patent: WO2005/9941, 2005, A1, . Location in patent: Page 43-44
[5] Patent: WO2011/33255, 2011, A1, . Location in patent: Page/Page column 72

3
[ 89280-91-1 ]
[ 76360-43-5 ]
[ 88770-19-8 ]

Reference： [1] Journal of Materials Chemistry, 1999, vol. 9, # 9, p. 2155 - 2163

4
[ 88-13-1 ]
[ 88770-19-8 ]

Reference： [1] Patent: WO2011/33255, 2011, A1,
[2] Tetrahedron Letters, 2013, vol. 54, # 11, p. 1460 - 1462
[3] Journal of Materials Chemistry C, 2018, vol. 6, # 14, p. 3731 - 3742

5
[ 100523-84-0 ]
[ 88770-19-8 ]

Reference： [1] Archiv der Pharmazie, 1998, vol. 331, # 12, p. 405 - 411

6
[ 67-56-1 ]
[ 98215-44-2 ]
[ 88770-19-8 ]

Reference： [1] Archiv der Pharmazie, 1998, vol. 331, # 12, p. 405 - 411

[ 88770-19-8 ] Synthesis Path-Downstream 1~59

1
[ 67-56-1 ]
[ 98215-44-2 ]
[ 88770-19-8 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 405 - 411

2
[ 58621-39-9 ]
[ 88770-19-8 ]
[ 219771-93-4 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 405 - 411

3
[ 89280-91-1 ]
[ 76360-43-5 ]
[ 88770-19-8 ]

Reference： [1]Journal of Materials Chemistry,1999,vol. 9,p. 2155 - 2163

4
[ 88770-19-8 ]
methyl 2-(tri-n-butylstannyl)-thiophene-3-carboxylate [ No CAS ]
dimethyl 2,2'-bithiophene-3,4'-dicarboxylate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 6931 - 6937

5
[ 88770-19-8 ]
dimethyl [2,2'-bithiophene]-4,4'-dicarboxylate [ No CAS ]

Reference： [1]Journal of Materials Chemistry C,2019,vol. 7,p. 9581 - 9590
[2]Journal of Materials Chemistry C,2018,vol. 6,p. 3731 - 3742
[3]Journal of Organic Chemistry,2002,vol. 67,p. 6931 - 6937
[4]Tetrahedron Letters,2013,vol. 54,p. 1460 - 1462

6
[ 100523-84-0 ]
[ 88770-19-8 ]

Reference： [1]Archiv der Pharmazie,1998,vol. 331,p. 405 - 411

7
[ 88770-19-8 ]
[ 98-80-6 ]
[ 38695-72-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80.0℃; for 24h;	Prepare a mixture of <strong>[88770-19-8]5-bromo-thiophene-3-carboxylic acid methyl ester</strong> (1.86 g, 8.41 mmol), phenylboronic acid (2. 05 g, 16.83 mmol), and 1 M aqueous potassium carbonate (12.5 mL, 25.23 mmol) in 1,2-dimethoxyethane (70 mL) and purge with nitrogen for 20 minutes. Add Pd (PPh3) 4 (485 mg, 0.42 mmol) and again purge the mixture with nitrogen for 10 minutes. Heat to 80C for 24 hours. Evaporate the solvent and redissolve the residue in ethyl acetate. Extract the aqueous phase with ethyl acetate (2 x 20 mL), wash the combined organic phases brine (40 mL), dry (magnesium sulfate), filter and concentrate. Perform flash chromatography on silica gel eluting with 10: 1 hexane/ethyl acetate to afford 947 mg of 5-phenylthiophene-3-carboxylic acid methyl ester as a white solid. MS: m/e= 219 [MH+].

Reference： [1]Patent: WO2005/9941,2005,A1 .Location in patent: Page 44

8
[ 67-56-1 ]
[ 100523-84-0 ]
[ 88770-19-8 ]

Yield	Reaction Conditions	Operation in experiment
91%		A solution of bromine (2 mL, 39.06 mmol) in glacial acetic acid (64 mL) was added slowly to a stirred solution of Int-1 (5 g, 39.06 mmol) in glacial acetic acid (37 mL) at 0 C. and stirred at room temperature for 20 minutes. The reaction mixture was then poured into ice water while stirring vigorously. The white precipitated solid was filtered, washed with water and recrystallised from hot water to afford pure Int-2 as white solid (3.68 g, 46%). 1H NMR (200 MHz, dmso-d6): delta 7.55 (s, 1H), 8.17 (s, 1H). To a stirred solution of Int-2 (3.4 g, 16.42 mmol) in methanol (40 mL) was added H2SO4 (321 mg, 3.28 mmol) and stirred under reflux for 12 hours. Volatiles from the reaction mixture were distilled off under reduced pressure and the resulting residue was extracted with DCM (75 mL). The organic extract was washed with water (40 mL), saturated aqueous NaHCO3 solution (40 mL), brine (40 mL) and dried over Na2SO4, filtered and concentrated under vacuum to afford pure Int-3 as colorless viscous oil (3.3 g, 91%). 1H NMR (200 MHz, dmso-d6): delta 7.98 (s, 1H), 7.44 (s, 1H), 3.87 (s, 3H). To a stirred solution of Int-3 (0.5 g, 2.26 mmol) in dioxane (25 mL) was added Int-4 (0.51 g, 2.26 mmol) followed by Pd (OAc) 2 (105 mg, 0.45 mmol), xanthpos (265 mg, 0.497 mmol) and CS2CO3 (1.18 g, 3.62 mmol). The reaction mixture was degassed under vacuum, bubbled with N2 for 10 minutes and stirred under reflux for 20 hours. The reaction mixture was concentrated under reduced pressure and was purified by column chromatography to isolate product and a very close spot together eluting with EtOAc. This mixture (140 mg) was further purified with preparative HPLC to obtain pure Int-5 as a yellow solid (80 mg, 10%). Mass (m/z): 366.0 [M++1]. 1H NMR (200 MHz, dmso-d6): 9.50 (d, J=7 Hz, 1H), 8.51 (d, J=7 Hz, 1H), 8.56 (d, J=5.2 Hz, 1H), 7.74 (brs, 1H), 7.66 (d, J=11.8 Hz, 1H), 7.35 (d, J=7.4 Hz, 1H), 7.11 (s, 1H), 7.02 (d, J=5.6 Hz, 1H), 6.87 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 2.73 (s, 3H). To a stirred solution of Int-5 (0.7 g, 1.91 mmol) in THF: MeOH: H2O (2:1:2) (50 ml) was added LiOH (0.24 g, 5.74 mmol) at room temperature and stirred while heating at 50 C. for 16 hours. Volatiles from the reaction mixture were distilled off under reduced pressure, the reaction mixture was acidified to about pH 5-6 with 2N HCl. The precipitated solid was filtered and dried under vacuum to afford pure Int-6 (0.51 g, 76%). Mass (m/z): 352.0 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 12.45 (brs, 1H), 10.87 (s, 1H), 9.70 ((brs, 1H), 8.60 (d, J=4.68 Hz, 1H), 7.67-7.59 (m, 2H), 7.45 (t, J=8.4 Hz, 1H), 7.13 (d, J=5.2 Hz, 1H), 7.04 (s, 2H), 2.65 (s, 3H).
	With hydrogenchloride; In water; for 3h;Heating / reflux;	Prepare a solution of <strong>[100523-84-0]5-bromothiophene-3-carboxylic acid</strong> (500 mg, 2.41 mmol) in methanol (5 mL). Add concentrated hydrochloric acid (0.1 mL). Reflux the mixture for 3 hours, cool to room temperature, pour into water, and extract with diethyl ether (3 X 10 mL). Wash the combined organic phases with water (10 mL), then saturated aqueous sodium hydrogencarbonate (10 mL). Dry (magnesium sulfate), filter and concentrate. Perform flash chromatography on silica gel eluting with 5: 1 HEXANE/ETHYL acetate to afford 409 mg of <strong>[100523-84-0]5-bromothiophene-3-carboxylic acid</strong> methyl ester as a white SOLID. 1H NMR (CDC13) 6 8.10 (d, J= 1.5 Hz, 1H), 7.17 (d, J= 1.5 Hz, 1H), 3.86 (s, 3H).
	With sulfuric acid; for 14h;Reflux;	5-Bromo-thiophene-3-carboxylic acid (13 g, 64 mmol) was dissolved in methanol (140 mL). Concentrated sulphuric acid (6.5 mL) was added and the mixture heated at reflux for 14 hours. The reaction was quenched by adding a solution of saturated aqueous sodium bicarbonate and most of the solvent was removed by evaporation under vacuum. The mixture was then diluted with a solution of saturated aqueous sodium bicarbonate and the product extracted with DCM. The organic solution was dried over sodium sulphate, filtered and the solvent removed by evaporation to give a white crystalline solid (13.2g). H NMR (400 MHz, CDCI3): delta 8.0 (s, 1 H), 7.5 (s, 1 H), 3.85 (s, 3H).

Reference： [1]Patent: US2010/29638,2010,A1 .Location in patent: Page/Page column 110
[2]Tetrahedron Letters,2013,vol. 54,p. 1460 - 1462
[3]Journal of Materials Chemistry C,2018,vol. 6,p. 3731 - 3742
[4]Patent: WO2005/9941,2005,A1 .Location in patent: Page 43-44
[5]Patent: WO2011/33255,2011,A1 .Location in patent: Page/Page column 72

9
[ 145214-05-7 ]
[ 88770-19-8 ]
[ 1187467-89-5 ]

Yield	Reaction Conditions	Operation in experiment
	tetrakis(triphenylphosphine) palladium(0); In toluene; at 100.0℃;Inert atmosphere;	Synthesis 36; 5-Oxazol-2-yl-thiophene-3-carboxylic acid methyl ester; Pd(PPh3J4, toluene delta-Bromo-thiophene-S-carboxylic acid methyl ester (0.3 g, 1.35 mmol) was dissolved in toluene (5 ml_), 2-tributylstannyl oxazole (0.311 ml_, 1.48 mmol) was added then the reaction mixture was purged with nitrogen before addition of palladium tetrakis(triphenylphosphine) (0.14 g, 0.12 mmol). The reaction mixture was heated at 1000C over the weekend. The mixture was filtered then evaporated and the residue was purified by chromatography on a silica Il cartridge, eluting with 10-20% DCM in pentane to give the title compound as a yellow solid (0.105 g). LCMS m/z 210 [M+H]+ and 251.23 [M+MeCN+H]+ RT. = 3.03 min (Analytical Method 6).

Reference： [1]Patent: WO2009/112845,2009,A1 .Location in patent: Page/Page column 112

10
[ 813-19-4 ]
[ 88770-19-8 ]
[ 1187467-91-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane;Inert atmosphere; Reflux;	Synthesis 38; 5-(1-Methyl-1 H-pyrazol-3-yl)-thiophene-3-carboxylic acid methyl ester; Pd(PPh3),, toluene delta-Bromo-thiophene-S-carboxylic acid methyl ester (0.484 g, 2.19 mmol), hexabutylditin (1.99 mL, 3.95 mmol) and triethylamine (7 mL) were dissolved in dioxane (15 mL) then the solution was degassed with nitrogen before the addition of palladium tetrakis(triphenylphosphine) (0.152 g, 0.13 mmol). The reaction mixture was heated to reflux overnight then filtered and evaporated. The crude material was purified by <n="115"/>chromatography on a silica Il cartridge, eluting with 2-10% DCM in pentane to afford 5- tributylstannanyl-thiophene-3-carboxylic acid methyl ester as a colourless oil (0.228 g).This material (0.225 g, 0.52 mmol) was dissolved in toluene (5 mL), 3-iodo-1-methyl-1 H- pyrazole (0.119 g, 0.57 mmol) was added then the reaction mixture was purged with nitrogen before addition of palladium tetrakis(triphenylphosphine) (0.06 g, 0.05 mmol). The reaction mixture was heated at 115C for two days then filtered and evaporated. The residue was purified by chromatography on a silica Il cartridge, eluting with 5-20% ethyl acetate in cyclohexane to give the title compound as a yellow-brown oil which solidified on standing (0.076 g). LCMS m/z 223.01 [M+H]+ and RT. = 3.04 min (Analytical Method 7).

Reference： [1]Patent: WO2009/112845,2009,A1 .Location in patent: Page/Page column 113-114

11
[ 552846-17-0 ]
[ 88770-19-8 ]
[ 1187468-01-4 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; industrial methylated spirit; water; at 110.0℃; for 6h;Inert atmosphere;	5-Bromo-thiophene-3-carboxylic acid methyl ester (6 g, 27 mmol) was dissolved in a mixture of DME (75 mL), IMS (25 mL) and water (12.5 mL). Caesium carbonate (13.2 g, 40 mmol) and 4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-pyrazole-1 -carboxylic acid tert-butyl ester (9.2 g, 31 mmol) were added and the mixture stirred under argon.Palladium tetrakis-(triphenylphosphine) (3.1 g, 2.7 mmol) was then added and the mixture heated at 110C for 6 hours. The mixture was allowed to cool to room temperature and then diluted with water. The product was extracted into DCM and washed with brine, then dried over sodium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was triturated with diethyl ether to give the title compound as a pale yellow solid (3.01 g). LCMS m/z 209.1 [M+H]+. R.T. = 3.72 min (Analytical Method 4). 1H NMR (400 MHz, d6-DMSO): delta 8.2 (s, 1 H), 8.15 (s, 1 H), 7.85 (s, 1H), 7.5 (s, 1 H), 3.8 (s, 3H).
	With water; caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; industrial methylated spirit; at 140.0℃; for 0.333333h;Microwave irradiation;	Synthesis 45; 5-(1 H-Pyrazol-4-yl)-thiophene-3-carboxylic acid; IMS, delta-Bromo-thiophene-S-carboxylic acid methyl ester (1.29 g, 5.84 mmol) was dissolved in DME (13.5 mL), IMS (4.5 mL) and water (2 ml_) and ), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (1.89 g, 6.43 mmol) and caesium carbonate (2.85 g, 8.77 mmol) were added followed by palladium tetrakis(triphenylphosphine) (0.675 g, 5.84 mmol). The reaction mixture was heated by microwave irradiation at 1400C for 20 minutes and then diluted with water and extracted with DCM (x 3). The organic solution was dried over sodium sulfate, filtered and the solvent evaporated. The residue was purified by chromatography on a silica Il cartridge, eluting with 10 to 50% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give 5-(1H-pyrazol-4-yl)-thiophene-3- carboxylic acid methyl ester as a white, flocculent solid (0.728 g).This material (0.725 g, 3.49 mmol) was dissolved in methanol (10 mL) and sodium hydroxide (1 M aqueous, 8.7 mL) was added. The reaction mixture was stirred for 3 hours at room temperature then a further 0.25 eq. of sodium hydroxide was added and the mixture stirred for 20 minutes. HCI (1 N, 7mL) was added and the mixture was concentrated. The residue was taken up in water and acidified (pH 2) and the resultant white precipitate was collected by filtration to afford the title compound as a white solid (0.5 g). LCMS m/z 236.30 (M + MeCN+H+). RT. = 2.31 min (Analytical Method 6).

Reference： [1]Patent: WO2011/33255,2011,A1 .Location in patent: Page/Page column 72
[2]Patent: WO2009/112845,2009,A1 .Location in patent: Page/Page column 119

12
[ 88770-19-8 ]
[ 847818-74-0 ]
[ 1187467-88-4 ]

Yield	Reaction Conditions	Operation in experiment
	With water; caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; industrial methylated spirit; at 140.0℃;Microwave irradiation;	Synthesis 34; 5-(2-Methyl-2H-pyrazol-3-yl)-thiophene-3-carboxylic acid; IMS, delta-Bromo-thiophene-S-carboxylic acid methyl ester (0.193 g, 0.87 mmol) was combined with 1-methyl-5-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-1 H-pyrazole (0.2 g, 0.96 mmol), caesium carbonate (0.424 g, 1.3 mmol), and palladium tetrakis(triphenylphosphine) (0.1 g, 0.09 mmol) in DME (10 ml_), IMS 2 mL) and water (1 mL). The reaction mixture was degassed then heated by microwave irradiation to 1400C for 20 minutes. The mixture was diluted with water then extracted with DCM (* 3) then the organic solution was dried over sodium sulfate, filtered and the solvent evaporated. The residue was purified by chromatography on a 5g silica Il cartridge, - eluting with 5-30% ethyl acetate in cyclohexane to give 5-(2-methyl-2H-pyrazol-3-yl)- thiophene-3-carboxylic acid methyl ester as a brown oil (0.163 g). LCMS m/z 223.24 [M+H]+ RT. = 3.24 min (Analytical Method 6).

Reference： [1]Patent: WO2009/112845,2009,A1 .Location in patent: Page/Page column 111

13
[ 88770-19-8 ]
4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine [ No CAS ]
[ 1204527-34-3 ]

Yield	Reaction Conditions	Operation in experiment
10%	With caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene;palladium diacetate; In 1,4-dioxane;Inert atmosphere; Reflux;	A solution of bromine (2 mL, 39.06 mmol) in glacial acetic acid (64 mL) was added slowly to a stirred solution of Int-1 (5 g, 39.06 mmol) in glacial acetic acid (37 mL) at 0 C. and stirred at room temperature for 20 minutes. The reaction mixture was then poured into ice water while stirring vigorously. The white precipitated solid was filtered, washed with water and recrystallised from hot water to afford pure Int-2 as white solid (3.68 g, 46%). 1H NMR (200 MHz, dmso-d6): delta 7.55 (s, 1H), 8.17 (s, 1H). To a stirred solution of Int-2 (3.4 g, 16.42 mmol) in methanol (40 mL) was added H2SO4 (321 mg, 3.28 mmol) and stirred under reflux for 12 hours. Volatiles from the reaction mixture were distilled off under reduced pressure and the resulting residue was extracted with DCM (75 mL). The organic extract was washed with water (40 mL), saturated aqueous NaHCO3 solution (40 mL), brine (40 mL) and dried over Na2SO4, filtered and concentrated under vacuum to afford pure Int-3 as colorless viscous oil (3.3 g, 91%). 1H NMR (200 MHz, dmso-d6): delta 7.98 (s, 1H), 7.44 (s, 1H), 3.87 (s, 3H). To a stirred solution of Int-3 (0.5 g, 2.26 mmol) in dioxane (25 mL) was added Int-4 (0.51 g, 2.26 mmol) followed by Pd (OAc) 2 (105 mg, 0.45 mmol), xanthpos (265 mg, 0.497 mmol) and CS2CO3 (1.18 g, 3.62 mmol). The reaction mixture was degassed under vacuum, bubbled with N2 for 10 minutes and stirred under reflux for 20 hours. The reaction mixture was concentrated under reduced pressure and was purified by column chromatography to isolate product and a very close spot together eluting with EtOAc. This mixture (140 mg) was further purified with preparative HPLC to obtain pure Int-5 as a yellow solid (80 mg, 10%). Mass (m/z): 366.0 [M++1]. 1H NMR (200 MHz, dmso-d6): 9.50 (d, J=7 Hz, 1H), 8.51 (d, J=7 Hz, 1H), 8.56 (d, J=5.2 Hz, 1H), 7.74 (brs, 1H), 7.66 (d, J=11.8 Hz, 1H), 7.35 (d, J=7.4 Hz, 1H), 7.11 (s, 1H), 7.02 (d, J=5.6 Hz, 1H), 6.87 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 2.73 (s, 3H). To a stirred solution of Int-5 (0.7 g, 1.91 mmol) in THF: MeOH: H2O (2:1:2) (50 ml) was added LiOH (0.24 g, 5.74 mmol) at room temperature and stirred while heating at 50 C. for 16 hours. Volatiles from the reaction mixture were distilled off under reduced pressure, the reaction mixture was acidified to about pH 5-6 with 2N HCl. The precipitated solid was filtered and dried under vacuum to afford pure Int-6 (0.51 g, 76%). Mass (m/z): 352.0 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 12.45 (brs, 1H), 10.87 (s, 1H), 9.70 ((brs, 1H), 8.60 (d, J=4.68 Hz, 1H), 7.67-7.59 (m, 2H), 7.45 (t, J=8.4 Hz, 1H), 7.13 (d, J=5.2 Hz, 1H), 7.04 (s, 2H), 2.65 (s, 3H).

Reference： [1]Patent: US2010/29638,2010,A1 .Location in patent: Page/Page column 110

14
[ 88-13-1 ]
[ 88770-19-8 ]

Reference： [1]Patent: WO2011/33255,2011,A1
[2]Tetrahedron Letters,2013,vol. 54,p. 1460 - 1462
[3]Journal of Materials Chemistry C,2018,vol. 6,p. 3731 - 3742

15
[ 88770-19-8 ]
[ 1187468-02-5 ]

Reference： [1]Patent: WO2011/33255,2011,A1
[2]Patent: WO2009/112845,2009,A1

16
[ 88770-19-8 ]
[ 1274933-22-0 ]

Reference： [1]Patent: WO2011/33255,2011,A1

17
[ 1295649-89-6 ]
[ 88770-19-8 ]
[ 1295649-67-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 3945 - 3959

18
[ 1295649-89-6 ]
[ 88770-19-8 ]
C₂₆H₂₈O₁₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 3945 - 3959

19
[ 88770-19-8 ]
[ 1423116-05-5 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 1460 - 1462

20
[ 88770-19-8 ]
[ 1423116-06-6 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 1460 - 1462

21
[ 88770-19-8 ]
[ 1423116-07-7 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 1460 - 1462

22
[ 88770-19-8 ]
[ 1423116-04-4 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 1460 - 1462

23
[ 88770-19-8 ]
[ 927-74-2 ]
5-(4-hydroxybut-1-ynyl)thiophene-3-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

24
[ 88770-19-8 ]
5-(4-hydroxybutyl)thiophene-3-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

25
[ 88770-19-8 ]
5-(3-carboxypropyl)thiophene-3-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

26
[ 88770-19-8 ]
5-[3-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)propyl]thiophene-3-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

27
[ 88770-19-8 ]
5-[3-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)propyl]thiophene-3-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

28
[ 88770-19-8 ]
(S)-2-({5-[3-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)propyl]thiophene-3-carbonyl}amino)pentanedioic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

29
[ 88770-19-8 ]
5-[3-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)propyl]thiophene-3-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

30
[ 88770-19-8 ]
5-[3-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)propyl]thiophene-3-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

31
[ 88770-19-8 ]
(S)-2-({5-[3-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)propyl]thiophene-3-carbonyl}amino)pentanedioic acid diethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

32
[ 88770-19-8 ]
(S)-2-({5-[3-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)propyl]thiophene-3-carbonyl}amino)pentanedioic acid diethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

33
[ 88770-19-8 ]
(S)-2-({5-[3-(2,4-diamino-furo[2,3-d]pyrimidin-5-yl)propyl]thiophene-3-carbonyl}amino)pentanedioic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

34
[ 88770-19-8 ]
C₁₀H₁₁ClO₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

35
[ 88770-19-8 ]
C₁₁H₁₂N₂O₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

36
[ 88770-19-8 ]
C₁₁H₁₃ClO₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959

37
[ 88770-19-8 ]
bis(2-ethylhexyl) 5,5'-dibromo-[2,2'-bithiophene]-4,4'-dicarboxylate [ No CAS ]

Reference： [1]Journal of Materials Chemistry C,2018,vol. 6,p. 3731 - 3742

38
[ 88770-19-8 ]
bis(2-butyloctyl) 5,5'-dibromo-[2,2'-bithiophene]-4,4'-dicarboxylate [ No CAS ]

Reference： [1]Journal of Materials Chemistry C,2018,vol. 6,p. 3731 - 3742

39
[ 88770-19-8 ]
bis(2-hexyldecyl) 5,5'-dibromo-[2,2'-bithiophene]-4,4'-dicarboxylate [ No CAS ]

Reference： [1]Journal of Materials Chemistry C,2018,vol. 6,p. 3731 - 3742

40
[ 88770-19-8 ]
dimethyl 5,5'-dibromo-[2,2'-bithiophene]-4,4'-dicarboxylate [ No CAS ]

Reference： [1]Journal of Materials Chemistry C,2018,vol. 6,p. 3731 - 3742
[2]Journal of Materials Chemistry C,2019,vol. 7,p. 9581 - 9590

41
[ 88770-19-8 ]
[ 1044851-90-2 ]