[ CAS No. 814918-95-1 ] {[proInfo.proName]}

Name: 814918-95-1|5-Bromo-4-chlorothieno[2,3-d]pyrimidine|95%
Brand: Ambeed
SKU: A187961
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Quality Control of [ 814918-95-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 814918-95-1 ]

SDS Specification

Alternatived Products of [ 814918-95-1 ]

Product Details of [ 814918-95-1 ]

CAS No. :	814918-95-1	MDL No. :	MFCD11042739
Formula :	C₆H₂BrClN₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IKCKRHCJPVDELP-UHFFFAOYSA-N
M.W :	249.52	Pubchem ID :	45480299
Synonyms :

Calculated chemistry of [ 814918-95-1 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	50.13
TPSA :	54.02 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) :	-5.54 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.15
Log Po/w (XLOGP3) :	3.21
Log Po/w (WLOGP) :	3.11
Log Po/w (MLOGP) :	2.01
Log Po/w (SILICOS-IT) :	4.0
Consensus Log Po/w :	2.9

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.01
Solubility :	0.0241 mg/ml ; 0.0000967 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.02
Solubility :	0.024 mg/ml ; 0.0000962 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.07
Solubility :	0.0212 mg/ml ; 0.0000849 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.43

Safety of [ 814918-95-1 ]

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

Application In Synthesis of [ 814918-95-1 ]

* 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 [ 814918-95-1 ]
Downstream synthetic route of [ 814918-95-1 ]

[ 814918-95-1 ] Synthesis Path-Upstream 1~6

1
[ 56844-12-3 ]
[ 814918-95-1 ]

Yield	Reaction Conditions	Operation in experiment
67.1%	With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 1 h; Inert atmosphere	[0123] To diisopropylamine (1.028 ml, 7.21 mmol, 1.8 equiv) in 10 mL THF at 0 °C was added n-butyl lithium (3.76 ml, 6.01 mmol, 1.5 equiv). After 1 h, the LDA solution was transferred to a solution of 6-bromo-4-chlorothieno[2,3-d]pyrimidine (1.0 g, 4.01 mmol, 1.0 equiv) in 35 mL THF at -78 °C under nitrogen. The solution stirred for 1 h at -78 °C after which a mixture of 1.25 mL water and 5 mL THF was added slowly. The mixture was then warmed to 0 °C, poured into 60 mL water, and extracted with dichloromethane. The combined organic extracts were then dried over Na2SC> , filtered, and concentrated in vacuo to give a yellow solid which was chromatographed with 20percent EtOAc/Hexanes gradient elution to give 5-bromo-4-chlorothieno[2,3-d]pyrimidine (671 mg, 67.1 percent yield) as a tan solid. NMR (400 MHz, chloroform- ) δ ppm 8.85 (s, 1 H), 7.64 (s, 1 H).
56%	With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -78℃; for 1 h; Inert atmosphere	Step 4: To a stirred solution of 6-bromo-4-chlorothieno[2,3-c]pyrimidine (3 g, 12.048 mmol) in THF (120 mL) was added 2M LDA solution in THF/heptane/ethylbenzene (9 mL, 18.072 mmol) at -78 °C under nitrogen. The reaction mixture was stirred for 1 h at -78 °C, a mixture of 3.75 mL water and 15 mL THF was added slowly. The mixture was warmed to 0 °C, poured onto water (180 mL). The reaction mixture was extracted with dichloromethane (2 x 50 mL). The combined organic extracts were dried over Na₂S0₄, filtered, and concentrated in vacuo to give crude product. The crude product was purified by flash column chromatography with 80 g silica column and 10percent EtOAc in Hexanes as eluent to give 5-bromo-4-chlorothieno[2,3- cdpyrimidine as yellow solid (1.7 g, 56percent). LCMS (ES) m/z = 248.9, 250.9 [M+H]⁺. H NMR (400 MHz, CDCI₃) δ ppm 7.66 (s, 1 H), 8.87 (s, 1 H).
55%	Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -100 - 0℃; for 0.916667 h; Stage #2: With ammonium chloride In tetrahydrofuran; water	Lithium diisopropylamine (LDA) was prepared by addition of 2.5 molar BuLi (3.0 mL, 7.6 mmol) in hexanes to a ca. -50° C. solution of diisopropylamine (1.1 mL, 790 mg, 7.8 mmol) in anhydrous THF (15 mL). The solution was warmed to 0° C. for 10 min and then added dropwise to a solution of 6-bromo-4-chlorothieno[2,3-d]pyrimidine (which was prepared as disclosed in WO 2003053446) (2.0 g, 8.0 mmol) in THF (30 mL) cooled to -100° C. The mixture was maintained at -90 to -100° C. for 45 minutes and then quenched with saturated aqueous NH₄Cl. The mixture was diluted with ethyl acetate (30 mL) and the separated organic phase was washed with water, brine, dried (Na₂SO₄) and evaporated. The residue was recrystallized from aqueous ethanol and the isolated solid was dissolved in dichloromethane and passed through a silica gel plug eluting with dichloromethane to yield 900 mg of material. A further 200 mg of product was obtained from the evaporated, recrystallization filtrate by reverse phase High Pressure Liquid Chromatography (HPLC) on a 50 mm.x.250 mm YMC-AQ eluting with 70/30 acetonitrile/0.1 percent v/v water-conc. H₂PO₄. Total yield was 1.1 g (55 percent). In later runs the crude bromide was recrystallized from acetonitrile.

46%

With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1 h; Inert atmosphere

To a stirred solution of 6-bromo-4-chlorothieno[2,3-c]pyrimidine (1 g, 4.0 mmol, 1 equiv) in THF (40 mL) was added 2M LDA in THF solution (3 mL, 6.0 mmol, 1.5 equiv) drop wise at -78 °C under nitrogen. The reaction was stirred for 1 h at -78 °C after which a mixture of water (1.25 mL) and THF (5 mL) was added slowly. The mixture was then warmed to 0 °C, poured onto water (60 mL), and extracted with DCM (2 x 30 mL). The combined organic extracts were combined and dried over Na₂S0₄, filtered and concentrated. Purification: Purified by flash column chromatography, 24g silica column with 10percent EtOAc in hexane as mobile phase to give 5-bromo-4-chlorothieno[2,3-c]pyrimidine as yellow solid. Yield (0.46 g, 46 percent). LC-MS (ES) m/z = 248.9 [M+H]⁺. H NMR (400 MHz, CDCI₃) δ 7.66 (s, 1 H), 8.87 (s, 1 H).

Reference： [1] Patent: WO2012/44993, 2012, A1, . Location in patent: Page/Page column 44
[2] Patent: WO2017/46739, 2017, A1, . Location in patent: Page/Page column 53
[3] Patent: US2006/89370, 2006, A1, . Location in patent: Page/Page column 13-14
[4] Patent: WO2015/136463, 2015, A1, . Location in patent: Page/Page column 137
[5] Patent: WO2004/111057, 2004, A1, . Location in patent: Page 58-59

2
[ 14080-50-3 ]
[ 814918-95-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5521 - 5527
[2] Patent: WO2012/44993, 2012, A1,

3
[ 14080-50-3 ]
[ 814918-95-1 ]

Reference： [1] Patent: WO2015/136463, 2015, A1,
[2] Patent: WO2017/46739, 2017, A1,

4
[ 4651-82-5 ]
[ 814918-95-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5521 - 5527

5
[ 1239460-82-2 ]
[ 814918-95-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5521 - 5527

6
[ 56844-40-7 ]
[ 814918-95-1 ]

Reference： [1] Patent: WO2012/44993, 2012, A1,

[ 814918-95-1 ] Synthesis Path-Downstream 1~57

1
[ 814918-95-1 ]
(5-bromothieno[2,3-d]pyrimidin-4-yl)pyridin-2-ylmethylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2-(Aminomethyl)pyridine; triethylamine; In ethanol; for 2.5h;Heating / reflux;	A stirred mixture of <strong>[814918-95-1]5-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (3.8g, 15.2mmol), ethanol (250ml), triethylamine (2.32ml, 16.7mmol) and 2-aminomethylpyridine (1.72ml, 16.7mmol) was heated under reflux for 2.5 hours. The solution was then cooled to ambient temperature, poured into water (300ml) and extracted with dichloromethane (3xl50ml). The combined organic extracts were dried (MgSO4) and the solvent removed in vacuo to give the crude product. Purification by flash chromatography (silica) eluting with ethyl acetate and 40-60 petroleum ether (1:1) gave (5-bromothieno[2,3-cf]pyrimidin-4-yl)pyridin-2-ylmethylamine as a yellow solid (3.12g), m.pt. 127-129C.

Reference： [1]Patent: WO2004/111057,2004,A1 .Location in patent: Page 59

2
[ 56844-12-3 ]
[ 814918-95-1 ]

Yield	Reaction Conditions	Operation in experiment
67.1%	With n-butyllithium; diisopropylamine; In tetrahydrofuran; at -78℃; for 1h;Inert atmosphere;	[0123] To diisopropylamine (1.028 ml, 7.21 mmol, 1.8 equiv) in 10 mL THF at 0 C was added n-butyl lithium (3.76 ml, 6.01 mmol, 1.5 equiv). After 1 h, the LDA solution was transferred to a solution of <strong>[56844-12-3]6-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (1.0 g, 4.01 mmol, 1.0 equiv) in 35 mL THF at -78 C under nitrogen. The solution stirred for 1 h at -78 C after which a mixture of 1.25 mL water and 5 mL THF was added slowly. The mixture was then warmed to 0 C, poured into 60 mL water, and extracted with dichloromethane. The combined organic extracts were then dried over Na2SC> , filtered, and concentrated in vacuo to give a yellow solid which was chromatographed with 20% EtOAc/Hexanes gradient elution to give 5-bromo-4-chlorothieno[2,3-d]pyrimidine (671 mg, 67.1 % yield) as a tan solid. NMR (400 MHz, chloroform- ) delta ppm 8.85 (s, 1 H), 7.64 (s, 1 H).
56%	With lithium diisopropyl amide; In tetrahydrofuran; n-heptane; ethylbenzene; at -78℃; for 1h;Inert atmosphere;	Step 4: To a stirred solution of 6-bromo-4-chlorothieno[2,3-c]pyrimidine (3 g, 12.048 mmol) in THF (120 mL) was added 2M LDA solution in THF/heptane/ethylbenzene (9 mL, 18.072 mmol) at -78 C under nitrogen. The reaction mixture was stirred for 1 h at -78 C, a mixture of 3.75 mL water and 15 mL THF was added slowly. The mixture was warmed to 0 C, poured onto water (180 mL). The reaction mixture was extracted with dichloromethane (2 x 50 mL). The combined organic extracts were dried over Na2S04, filtered, and concentrated in vacuo to give crude product. The crude product was purified by flash column chromatography with 80 g silica column and 10% EtOAc in Hexanes as eluent to give 5-bromo-4-chlorothieno[2,3- cdpyrimidine as yellow solid (1.7 g, 56%). LCMS (ES) m/z = 248.9, 250.9 [M+H]+. H NMR (400 MHz, CDCI3) delta ppm 7.66 (s, 1 H), 8.87 (s, 1 H).
55%		Lithium diisopropylamine (LDA) was prepared by addition of 2.5 molar BuLi (3.0 mL, 7.6 mmol) in hexanes to a ca. -50 C. solution of diisopropylamine (1.1 mL, 790 mg, 7.8 mmol) in anhydrous THF (15 mL). The solution was warmed to 0 C. for 10 min and then added dropwise to a solution of <strong>[56844-12-3]6-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (which was prepared as disclosed in WO 2003053446) (2.0 g, 8.0 mmol) in THF (30 mL) cooled to -100 C. The mixture was maintained at -90 to -100 C. for 45 minutes and then quenched with saturated aqueous NH4Cl. The mixture was diluted with ethyl acetate (30 mL) and the separated organic phase was washed with water, brine, dried (Na2SO4) and evaporated. The residue was recrystallized from aqueous ethanol and the isolated solid was dissolved in dichloromethane and passed through a silica gel plug eluting with dichloromethane to yield 900 mg of material. A further 200 mg of product was obtained from the evaporated, recrystallization filtrate by reverse phase High Pressure Liquid Chromatography (HPLC) on a 50 mm×250 mm YMC-AQ eluting with 70/30 acetonitrile/0.1 percent v/v water-conc. H2PO4. Total yield was 1.1 g (55 percent). In later runs the crude bromide was recrystallized from acetonitrile.

46%	With lithium diisopropyl amide; In tetrahydrofuran; at -78℃; for 1h;Inert atmosphere;	To a stirred solution of 6-bromo-4-chlorothieno[2,3-c]pyrimidine (1 g, 4.0 mmol, 1 equiv) in THF (40 mL) was added 2M LDA in THF solution (3 mL, 6.0 mmol, 1.5 equiv) drop wise at -78 C under nitrogen. The reaction was stirred for 1 h at -78 C after which a mixture of water (1.25 mL) and THF (5 mL) was added slowly. The mixture was then warmed to 0 C, poured onto water (60 mL), and extracted with DCM (2 x 30 mL). The combined organic extracts were combined and dried over Na2S04, filtered and concentrated. Purification: Purified by flash column chromatography, 24g silica column with 10% EtOAc in hexane as mobile phase to give 5-bromo-4-chlorothieno[2,3-c]pyrimidine as yellow solid. Yield (0.46 g, 46 %). LC-MS (ES) m/z = 248.9 [M+H]+. H NMR (400 MHz, CDCI3) delta 7.66 (s, 1 H), 8.87 (s, 1 H).
		A stirred solution of <strong>[56844-12-3]6-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (4.0g, 0.016mol) in anhydrous tetrahydrofuran (100ml) was cooled in a dry-ice/acetone bath and treated, under a nitrogen atmosphere, with lithium diisopropylamide (1.8M solution in tetrahydrofuran, 9.0ml, 0.016mol) over about 20 minutes. The resultant dark solution was stirred in the cold for 1 hour and then treated with a mixture of water (5ml) and tetrahydrofuran (20ml) over about 20 minutes. The mixture was then allowed to warm up to about 0C before being poured into water (250ml) and extracted with dichloromethane (SxlOOml). The combined organic extracts were dried (MgSO4) and the solvent removed in vacuo to give the crude product. Purification by flashchromatography (silica) eluting with dichloromethane gave 5-bromo-4-chlorothieno[2,3-cQpyrimidine as a pale brown solid (3.8g).

Reference： [1]Patent: WO2012/44993,2012,A1 .Location in patent: Page/Page column 44
[2]Patent: WO2017/46739,2017,A1 .Location in patent: Page/Page column 53
[3]Patent: US2006/89370,2006,A1 .Location in patent: Page/Page column 13-14
[4]Patent: WO2015/136463,2015,A1 .Location in patent: Page/Page column 137
[5]Patent: WO2004/111057,2004,A1 .Location in patent: Page 58-59

3
1-(6-methoxypyridin-3-yl)ethanamine [ No CAS ]
[ 814918-95-1 ]
C₁₄H₁₃BrN₄OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With triethylamine; In N,N-dimethyl-formamide; at 60℃; for 4h;	A mixture of <strong>[814918-95-1]5-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (279 mg, 1.1 mmol), the amine (compound 117) (256 mg, 1.7 mmol) and triethylamine (170 mg, 1.7 mmol) in DMF (3 mL) was stirred at 60 C. for 4 hours. After cooling, the mixture was diluted with water (20 mL) and extracted with ether (3×25 mL). The combined organics were dried (Na2SO4), filtered and stripped leaving product as a yellow oil, 296 mg, 74 percent yield.

Reference： [1]Patent: US2006/89370,2006,A1 .Location in patent: Page/Page column 13

4
[ 814918-95-1 ]
[ 885229-27-6 ]

Yield	Reaction Conditions	Operation in experiment
71%		5-Bromo-4-chlorothieno[2,3-d]pyrimidine (1.0 g, 4.0 mmol) was partially dissolved in anhydrous THF (10 mL), cooled to 0 C. and treated over 1 minute with a 2.0 M THF solution of i-propylmagnesium chloride (3.0 mL, 6.0 mmol, 1.5 eq.). All solids went into solution. After stirring for 15 minutes, the mixture was treated dropwise with a solution of iodine (1.5 g, 6.0 mmol) in THF (8 mL), producing a copious precipitate. After 20 minutes, the reaction was quenched by addition of saturated aqueous NH4Cl and partitioned between ethyl acetate and water. The organic phase was washed with water, brine and dried (Na2SO4) to give 950 mg of the crude iodide-ca 90 percent pure by GC. This material was recrystallized from hot acetonitrile to give 840 mg (71 percent) of the purified iodide.
62.2%		Isopropylmagnesium chloride (1.614 ml, 3.23 mmol, 1.2 equiv) was added slowly to <strong>[814918-95-1]5-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (671 mg, 2.69 mmol, 1.0 equiv) in 10 mL THF at 0 C under nitrogen. The mixture was allowed to stir for 15 min after which a solution of iodine (819 mg, 3.23 mmol, 1.2 equiv) in 1.5 mL THF was added. The mixture stirred for 20 min. Upon completion, the reaction was quenched with sat. NH4CI. It was then extracted with EtOAc. The combined organic extracts were then washed with Na2S2C>3, water, and brine, dried over MgSC^and concentrated to give 4-chloro-5-iodothieno[2,3-d]pyrimidine(496 mg, 62.2 % yield) as a tan solid. The crude product was taken on without further purification.

Reference： [1]eLife,2017,vol. 6
[2]Patent: US2006/89370,2006,A1 .Location in patent: Page/Page column 15
[3]Patent: WO2012/44993,2012,A1 .Location in patent: Page/Page column 45

5
[ 814918-95-1 ]
[ 90642-63-0 ]
[ 885229-24-3 ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine; In N,N-dimethyl-formamide; at 25℃; for 20h;	A mixture of <strong>[814918-95-1]5-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (750 mg, 3.0 mmol), the amine hydrochloride (compound 117) (844 mg, 4.5 mmol) and triethylamine (606 mg, 6.0 mmol) in DMF (57 mL) was stirred at approximately 25 C. for 20 hours. After cooling, the mixture was diluted with water (20 mL) and extracted with ethyl acetate (3*25 mL). The combined organics were washed with water, saturated brine, and dried (Na2SO4). Filtration and removal of solvent gave crude material which was triturated with hexane, affording product as a tan solid, 840 mg, 2.3 mmol, 77 percent yield.

Reference： [1]Patent: US2006/89370,2006,A1 .Location in patent: Page/Page column 14

6
[ 814918-95-1 ]
[ 1461-22-9 ]
[ 885229-29-8 ]

Yield	Reaction Conditions	Operation in experiment
91%		<strong>[814918-95-1]5-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (3.0 g, 12 mmol) was dissolved in anhydrous THF (35 mL), cooled to 0 C. and treated in portions with a 2M THF solution of i-propylmagnesium chloride (6.8 mL, 13 mmol, 1.1 eq.). After 15 minutes the solution was treated in several portions with freshly distilled tributyltin chloride (5.0 mL, 5.9 g, 18 mmol, 1.5 eq.) and then allowed to warm to 25 C. and stir for 18 hours. The reaction was quenched by addition of saturated aqueous NH4Cl and worked up with EtOAc. The organic phase was washed with water, brine, dried (Na2SO4) and evaporated. The oily residue was stripped of volatiles by Kugelrohr distillation at 0.1 mm-pot temperature 80 C. The residue was subjected to chromatography on silica gel eluting with 3 percent EtOAc in hexanes to give the stannane-5.0 g (91 percent). This material was combined with F-TEDA (7.2 g, 20 mmol, 1.7 eq.) in acetonitrile (15 mL) and heated to 75 C. for 18 hours. After cooling, the mixture was diluted with 30 mL water and 50 mL EtOAc. The organic phase was separated and the aqueous phase was extracted with a further 50 mL EtOAc. The combined organic phases were stirred with 50 mL 10 percent aqueous NH4F solution for 1 hour. The precipitates were removed by filtration and the organic phase was washed with water, brine, dried (Na2SO4) and evaporated. The residue was Kugelrohr distilled at 0.1 mm and 4 g of a white solid was taken overhead. This material contained the desired 4-chloro-5-fluorothienopyrimidine, 4,5-dichloro and 4-chlorothienopyrimidine plus residual Bu3Sn components. This material was chromatographed on silica with 5 percent EtOAc/hexanes to give 790 mg of a white solid that was free of tributyltin residues. The 4-chloro-5-fluorothienopyrimidine was isolated by reverse phase-HPLC on a YMC-AQ column (50 mm×250 mm) by elution with 50 percent acetonitrile. Product was isolated as an off-white solid, 200 mg, 1.1 mmol, 8.9 percent yield.

Reference： [1]Patent: US2006/89370,2006,A1 .Location in patent: Page/Page column 15-16

7
[ 2949-92-0 ]
[ 814918-95-1 ]
[ 885229-30-1 ]

Yield	Reaction Conditions	Operation in experiment
45%		<strong>[814918-95-1]5-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (750 mg, 3.0 mmol) was partially dissolved in anh. THF (8 mL), cooled to 0 C. and treated in portions with a 2M THF solution of i-PrMgCl (2.0 mL, 4.0 mmol). After 20 minutes, this solution was treated dropwise with methylmethanethiosulfonate (460 mul, 570 mg, 4.5 mmol). The cooling bath was removed and the mixture was stirred for 4 hours at 25 C. The reaction was quenched with saturated aqueous NH4Cl and extracted with EtOAc. The organic phase was washed with water, brine, dried (Na2SO4) and evaporated to give 830 mg crude product-ca 80 percent pure by GC. The material was purified by recrystallization from hot heptane to give 350 mg (45 percent) yield of tan crystals.

Reference： [1]Patent: US2006/89370,2006,A1 .Location in patent: Page/Page column 16

8
[ 814918-95-1 ]
[ 1239460-84-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In ethanol; at 75℃; for 1h;	5-Bromo-4-chlorothieno[2,3-<;i]pyrimidine and hydrazine monohydrate (2 ml, 41.2 mmol) in absolute ethanol (10 ml) was heated to 75C. After stirring for 1 h, the solution was concentrated to yield 5-bromo-4-hydrazinylthieno[2,3-<;i]pyrimidine. Method [8] retention time 0.80 min by EtaPLC (M+ 245 and 247).

Reference： [1]Patent: WO2010/91310,2010,A1 .Location in patent: Page/Page column 104
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5521 - 5527

9
5-bromothieno[2,3-d]pyrimidin-4(3H)-one [ No CAS ]
[ 814918-95-1 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; at 100℃; for 0.5h;Microwave irradiation;	5-Bromothieno[2,3-<;f]pyrimidin-4(3H)-one in phosphorus(V) oxychloride (10 ml) was heated in a microwave at 1000C for 30 min. The solution was concentrated under reduced pressure to yield 5-bromo-4-chlorothieno[2,3-<;f]pyrimidine. Method [8] retention time 8.72 min by EtaPLC (M+ 249, 251, and 253) major peak intensities.

Reference： [1]Patent: WO2010/91310,2010,A1 .Location in patent: Page/Page column 104
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5521 - 5527

10
[ 4651-82-5 ]
[ 814918-95-1 ]