[ CAS No. 950577-02-3 ]

Name: 950577-02-3|6-Bromo-7-fluoroquinazolin-4-ol|98%
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Quality Control of [ 950577-02-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 950577-02-3 ]

CAS No. :	950577-02-3	MDL No. :	MFCD09907649
Formula :	C₈H₄BrFN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KBQBBYPXSOKJEI-UHFFFAOYSA-N
M.W :	243.03	Pubchem ID :	135742367
Synonyms :

Calculated chemistry of [ 950577-02-3 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	49.22
TPSA :	46.01 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) :	-6.14 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.97
Log Po/w (XLOGP3) :	2.31
Log Po/w (WLOGP) :	2.66
Log Po/w (MLOGP) :	2.23
Log Po/w (SILICOS-IT) :	2.52
Consensus Log Po/w :	2.34

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.37
Solubility :	0.103 mg/ml ; 0.000425 mol/l
Class :	Soluble
Log S (Ali) :	-2.91
Solubility :	0.296 mg/ml ; 0.00122 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.89
Solubility :	0.0312 mg/ml ; 0.000129 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.69

Safety of [ 950577-02-3 ]

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

Application In Synthesis of [ 950577-02-3 ]

* 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.

Downstream synthetic route of [ 950577-02-3 ]

[ 950577-02-3 ] Synthesis Path-Downstream 1~50

1
[ 16499-57-3 ]
[ 950577-02-3 ]

Yield	Reaction Conditions	Operation in experiment
87%	With bromine; In water; at 85℃; for 5h;	To a solution of 7-Fluoro-3H-quinazolin-4-one (2.84 g, 17.3 mmol) in water (50 mL) a bromine (2.05 mL, 51.9 mmol) was added dropwise and the mixture was stirred at 85C for five hours. The mixture left to cool at room temperature. The precipitate was filtered off and washed with water (10 mL) and the crude solid was dissolved in a hot mixture of isopropanole: methanol = 1:1 and left to crystalize in the fridge overnight. The precipitate was filtrated off and dried in vacuum oven leading 3.87 g (yield=87%) of compound (11) as yellowish solid. ESI-MS: m/z 243.04, 245.04 [M+H]+. 1H NMR 11: (300 MHz, DMSO-d6) delta/ppm: 12.72 (br.s., 1H) , 8.33 (d, J = 7.7 Hz, 1H), 8.18 (s, 1H) 7.65 (d, J = 9.9 Hz, 1H)
21%	With bromine; In water; at 80℃; for 20h;	Compound of Type R: 6-bromo-7-fluoroquinazoline-4(3H)-one 7-fluoroquinazoline-4(3H)-one (type Q) (14.2 g, 86 mmol) was suspended in water (250 mL), bromine (13.2 mL, 258 mmol) added and the mixture stirred 20 h at 80 C. The precipitate was filtered out and washed with water. (Yield: 4.5 g, 21%).

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4180 - 4182
[2]Patent: US2009/69320,2009,A1 .Location in patent: Page/Page column 67

2
[ 950577-02-3 ]
[ 950577-03-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; trichlorophosphate; at 100℃; for 1h;	6-bromo-4-chloro-7-fluoroquinazoline <strong>[950577-02-3]6-bromo-7-fluoroquinazoline-4(3H)-one</strong> (type R) (4.5 g, 18 mmol) was suspended in POCl3 (18 mL), DBU (1.9 mL, 12.7 mmol) added and the reaction mixture stirred 1 h at 100 C. The mixture was then concentrated by evaporation and the residue taken up in 150 mL of dichloromethane. It was extracted with water (150 mL) and 5% sodium hydroxide sol. (150 mL), the organic phase dried (MgSO4) and evaporated to low bulk. (Yield: 4.2 g, 87%)

Reference： [1]Patent: US2009/69320,2009,A1 .Location in patent: Page/Page column 67

3
[ 143945-65-7 ]
[ 3473-63-0 ]
[ 950577-02-3 ]

Yield	Reaction Conditions	Operation in experiment
79%		Anthranilic acid ED.5 (1 .00 g, 4.27 mmol) is placed in 2-methoxyethanol (2.0 mL), combined with formamidine acetate (890 mg, 8.55 mmol) and heated to 125C for 20 h. The reaction mixture is added to aqueous NH3 (200 mL, 0.01 M), the precipitate is filtered off, dried and quinazolone Z.8 (817 mg, 79 %) is obtained.
79%	In 2-methoxy-ethanol; at 125℃; for 20h;	Method of Synthesising the Quinazolines D.3 and D.3Anthranilic acid ED.5 (1.00 g, 4.27 mmol) is placed in 2-methoxyethanol (2.0 mL), combined with formamidine acetate (890 mg, 8.55 mmol) and heated to 125 C. for 20 h. The reaction mixture is added to aqueous NH3 (200 mL, 0.01 M), the precipitate is filtered off, dried and quinazolone Z.8 (817 mg, 79%) is obtained.Quinazolone Z.8 (817 mg, 3.36 mmol) is combined with SOCl2 (20 mL) and DMF (0.05 mL) and heated to 80 C. for 2 h. The solvent is removed and quinazoline D.3 (879 mg, 100%) is obtained.Quinazoline D*.3 (879 mg, 3.36 mmol) is combined with methylamine (30 mL, 2 M in THF) and stirred for 1 h at 20 C. The solvent is eliminated, the residue is purified by chromatography (35:65 to 80:20 in 12 min MeOH/H2O) and quinoline D.3 (555 mg, 65%; HPLC-MS: MS (M+H)+=256/258; tRet.=1.86 min; method FECBM4) is obtained.

Reference： [1]Patent: WO2011/131741,2011,A1 .Location in patent: Page/Page column 81
[2]Patent: US2012/94976,2012,A1 .Location in patent: Page/Page column 49

4
[ 950577-02-3 ]
6-(tert-butylsulfonyl)-N-(4,5-dimethyl-1H-pyrazol-3-yl)-7-fluoroquinazolin-4-amine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 6 h / 100 °C 2.1: Oxone / ethyl acetate; methanol; water / 16 h / 25 °C 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 34 h / 80 °C 4.1: 1 h / 80 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/128622, 2014, A1

5
[ 950577-02-3 ]
[ 1622327-44-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 6 h / 100 °C 2.1: Oxone / ethyl acetate; methanol; water / 16 h / 25 °C 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 34 h / 80 °C 4.1: 1 h / 80 °C 5.1: potassium <i>tert</i>-butylate / 96 h / 90 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/128622, 2014, A1

6
[ 950577-02-3 ]
[ 1622327-45-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 6 h / 100 °C 2.1: Oxone / ethyl acetate; methanol; water / 16 h / 25 °C 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 34 h / 80 °C 4.1: 1 h / 80 °C 5.1: ethanol / 2 h / 80 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/128622, 2014, A1

7
[ 950577-02-3 ]
C₁₂H₁₂ClFN₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 6 h / 100 °C 2.1: Oxone / ethyl acetate; methanol; water / 16 h / 25 °C 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 34 h / 80 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/128622, 2014, A1

8
[ 950577-02-3 ]
[ 1622327-41-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 6 h / 100 °C 2.1: Oxone / ethyl acetate; methanol; water / 16 h / 25 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/128622, 2014, A1

9
[ 950577-02-3 ]
[ 75-66-1 ]
[ 1622327-42-7 ]

Yield	Reaction Conditions	Operation in experiment
61.9%	Stage #1: 6-bromo-7-fluoroquinazolin-4-ol With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In N,N-dimethyl-formamide for 0.0833333h; Inert atmosphere; Stage #2: 2-methylpropan-2-thiol In N,N-dimethyl-formamide at 100℃; for 6h;	1.1 Step 1: 6-(tert-butylthio)-7-fluoroquinazolin-4-ol Step 1: 6-(tert-butylthio)-7-fluoroquinazolin-4-ol: A mixture of 6-bromo-7- fluoroquinazolin-4-ol (69 g, 285 mmol), tetrakis(triphenylphosphine)-palladium(0) (20 g,17 mmol) and sodium carbonate (60 g, 570 mmol) was stirred in DMF (1 L) while purging with nitrogen gas for 5 minutes. 2-Methylpropane-2-thiol (64 ml, 570 mmol) was added and the reaction mixture was heated under reflux condenser for 6 hours at 100 °C. The reaction was cooled and filtered thru glass filter paper, and then poured slowly into 1500 mL of stirring water. The resulting red precipitate was filtered and triturated with 200mLEtOAc. The solid was filtered and washed sequentially with 110 mL hexanes, 150 mL of90:10 hexanes:EtOAc to give 6-(tert-butylthio)-7-fluoroquinazolin-4-ol (44.5g, 6 1.9%yield) as a tan solid. LC/MS: M+H = 253.2 ‘HNMR (400 IVIHz, DMSO-d6) ö ppm 12.23- 12.72 (m, 1 H), 8.24 (d, J=8.1 Hz, 1 H), 8.19 (s, 1 H), 7.58 (d, J=9.6 Hz, 1 H), 1.28 (s, 9H).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/128622, 2014, A1 Location in patent: Page/Page column 23

10
[ 950577-02-3 ]
[ 86087-23-2 ]
6-bromo-7-[(3S)-tetrahydrofuran-3-yl]oxy-3H-quinazolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%		Sodium hydride (60% disperse in mineral oil; 2.23 g, 55.8 mmol) and (S)-Tetrahydro-furan-3-ol (8.1 g, 93.0 mmol) were mixed together at 0C for 20 minutes following by addition of 6-Bromo-7-fluoro-3H-quinazolin-4-one (2.24 g, 9.228 mmol) and solution was heated at 130C for two hours. The reaction mixture was quenched with 40 mL of water and neutralized with 6 N HCl and the solution was extracted with EtOAc (3 x 80 mL), solvent dried on sodium sulphate and evaporated. The crude product was recrystallize from boiling isopropanol and crystals were collected by filtration. However, the compound 10 was still contaminated by 5% of isomer 8 and purified by flash chromatography, using 100 g silica SNAP column and DCM:MeOH solvent system (gradient 0-10% of MeOH in 15 CV). After evaporation of solvent 1.27 g (yield=44.3%) of pure compound 10 was isolated. mp > 270C. [a]20589=-23.1. ESI-MS: m/z 311.03, 313.06 [M+H]+. IR (KBr) nu/cm-1: 3434, 1641, 1461, 1436, 1267, 1016. 1H NMR (600 MHz, DMSO-d6) delta/ppm: 12.18 (s, 1H), 8.22 (s, 1H), 8.11 (d, J=3.40 Hz, 1H), 7.24 (s, 1H), 5.30-5.34 (m, 1H), 3.95-3.99 (m, 1H), 3.86-3.91 (m, 1H), 3.78-3.82 (m, 1H), 2.29-2.36 (m, 1H) 2.00-2.06 (m, 1H). 13C NMR (151 MHz, DMSO-d6) delta/ppm: 159.26, 157.72, 150.03, 146.49, 130.00, 117.05, 111.32, 110.39, 79.22, 72.06, 66.47, 32.38

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4180 - 4182

11
[ 950577-02-3 ]
[ 850140-72-6 ]

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4180 - 4182

12
[ 950577-02-3 ]
C₁₈H₁₄BrClFN₃O₂ [ No CAS ]

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4180 - 4182

13
[ 950577-02-3 ]
6-bromo-4-chloro-7-[(S)-(tetrahydro-furan-3-yl)oxy]-quinazoline [ No CAS ]

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4180 - 4182

14
[ 557-21-1 ]
[ 950577-02-3 ]
7-fluoro-4-hydroxyquinazolin-6-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1-methyl-pyrrolidin-2-one at 160℃; for 1h; Microwave irradiation; Inert atmosphere;	2.ff.iv iv. PREPARATION OF 7-FLuORO-4-HYDROxYQuINAzOLINE-6- CARBONITRILE (1.49) To a stirred solution of 1.12 (700 mg, 2.88 mmol) in NMP (17 mL) taken in a microwave vial was charged with Zn(CN)2 (676 mg, 5.76 mmol) and was degassed with argon for 10 mi Pd(PPh3)4 (332 mg, 0.28 mmol) was added to the reaction mixture under Ar (g) atmosphere and the reaction mixture was again purged with argon for 5 mm. The microwave vial was sealed and irradiated at 160 °C in CEM-microwave instrument for 1 h. Upon complete consumption of starting material, the reaction mixture was poured into water (25 mL), extracted with EtOAc (2 x 25 mL). The combined organic extracts were washed with water (25 mL), brine (25 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting (EtOAc: hexanes; 8: 2). Fractions containing the product were combined and concentrated under reduced pressure to afford 1.49 (490 mg, 90%) as an off-white solid. ‘H NIVIR (400 IVIFIz, DMSO-d6) (5: 12.73 (br s, 1H), 8.64 (d, J= 7.2 Hz, 1H), 8.29 (d, J= 3.6 Hz, 1H), 7.76 (d, J 10.4 Hz, 1H). LCMS (ESI): m/z = 188 [M + H]t

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF ALABAMA SYSTEM; SOUTHERN RESEARCH INSTITUTE - WO2019/89693, 2019, A1 Location in patent: Paragraph 00512

15
[ 950577-02-3 ]
4-chloro-7-fluoroquinazolin-6-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1-methyl-pyrrolidin-2-one / 1 h / 160 °C / Microwave irradiation; Inert atmosphere 2: thionyl chloride / 2 h / 20 - 80 °C

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF ALABAMA SYSTEM; SOUTHERN RESEARCH INSTITUTE - WO2019/89693, 2019, A1

16
[ 950577-02-3 ]
N-((1-(6-cyano-7-fluoroquinazolin-4-yl)-3-hydroxypiperidin-3-yl)methyl)methanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1-methyl-pyrrolidin-2-one / 1 h / 160 °C / Microwave irradiation; Inert atmosphere 2: thionyl chloride / 2 h / 20 - 80 °C 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / 20 °C

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF ALABAMA SYSTEM; SOUTHERN RESEARCH INSTITUTE - WO2019/89693, 2019, A1

17
[ 950577-02-3 ]
[ 950577-03-4 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; N,N-dimethyl-formamide at 80℃; for 2h;	2.q.i 1. PREPARATION OF 6-BR0M0-4-cHLoRo-7- FLUOROQUINAZOLINE (1.13) To a stirred solution of 6-bromo-7-fluoroquinazolin-4-ol 1.12 (200 mg, 0.81 mmol) in SOC12 (5.0 mL) was added DMF (0.1 mL) (catalytic) at 0 °C, the reaction mixture was stirred at 80 °C for 2 h. Upon complete consumption of starting material, the reaction mixture was concentrated under reduced pressure. Co-distilled with toluene (3 x 25 mL) to afford 1.13 (180 mg, crude) as a yellow solid. MS (MM): m/z 262.9 [M+H]t

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF ALABAMA SYSTEM; SOUTHERN RESEARCH INSTITUTE - WO2019/89693, 2019, A1 Location in patent: Paragraph 00464

18
[ 950577-02-3 ]
[ 100-39-0 ]
3-benzyl-6-bromo-7-fluoroquinazolin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In acetonitrile

Reference： [1]Xu, Guozhang; Gaul, Michael D.; Liu, Zhijie; DesJarlais, Renee L.; Qi, Jenson; Wang, Weixue; Krosky, Daniel; Petrounia, Ioanna; Milligan, Cynthia M.; Hermans, An; Lu, Hua-Rong; Huang, Devine Zheng; Xu, June Zhi; Spurlino, John C. [Bioorganic and Medicinal Chemistry Letters, 2020, vol. 30, # 23]

19
[ 950577-02-3 ]
[ 100-39-0 ]
3-benzyl-7-fluoro-6-(1H-pyrazol-4-yl)quinazolin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile 2: potassium carbonate / 1,4-dioxane

20
[ 950577-02-3 ]
[ 1247000-92-5 ]
7-fluoro-6-(4-(1-methylpiperidin-4-yl)phenyl)quinazolin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous sodium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 100℃; for 3h; Inert atmosphere;	1 7-Fluoro-6-(4-(1-methylpiperidin-4-yl)phenyl)quinazolin-4(3H)-one A mixture of 6-bromo-7-fluoroquinazolin-4(3H)-one (100 mg, 0.4 mmol), 1-methyl-4-(4~(4,4,5,5-tetrameibyl-1 ,3,2-dioxaborolan-2-yi)pheny)piperidine (187 mg, 0.6 mmol), Pd(dppf)Cl2.DCM (67 mg, 0.08 mmol) and sodium carbonate (131 mg, 1.2 mmol) in dioxane:water (4: 1 , 4 mL) was degassed and re-suffused with nitrogen three times. The mixture was heated at 100°C for 3 hours. After cooling, the reaction mixture was filtered and concentrated, and the residue was purified by reverse phase HPLC, eluting with 0-80% ACN/water (Q.035% TFA modifier). The product was dissolved in ethyl acetate and washed with saturated Na2C03and saturated brine, dried (MgS0 ), filtered, and concentrated under reduced pressure to give the title compound (24 mg, 17%). NMR (500 MHz, DMSO-cfe) d ppm 8.17 (d, 1 H) 8.15 (s, 1 H) 7.55 (m, 3H) 7.40 (d, 2H) 2.88 (d, 2H) 2.21 (s, 3H) 1.98 (m,2H) 1.78 (m,2H) 1.70 (m, 2H) one proton masked by solvent peak.
17%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous sodium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 100℃; for 3h; Inert atmosphere;	7-Fluoro-6-(4-(1-methylpiperidin-4-yl)phenyl)quinazolin-4(3H)-one (44) A mixture of 6-bromo-7-fluoroquinazolin-4(3H)-one (100 mg, 0.4 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (187 mg, 0.6 mmol), Pd(dppf)Cl2.DCM (67 mg, 0.08 mmol) and sodium carbonate (131 mg, 1.2 mmol) in dioxane:water (4:1, 4 mL) was degassed and re-suffused with nitrogen three times. The mixture was heated at 100°C for 3 hours. After cooling, the reaction mixture was filtered and concentrated, and the residue was purified by reverse phase HPLC, eluting with 0-80% ACN/water (0.035% TFA modifier). The product was dissolved in ethyl acetate and washed with saturated Na2CO3 and saturated brine, dried (MgSO4), filtered, and concentrated under reduced pressure to give the title compound (24 mg, 17%). 1H NMR (500 MHz, DMSO-d6) d ppm 8.17 (d, 1H) 8.15 (s, 1H) 7.55 (m, 3H) 7.40 (d, 2H) 2.88 (d, 2H) 2.21 (s, 3H) 1.98 (m, 2H) 1.78 (m,2H) 1.70 (m, 2H) one proton masked by solvent peak.
17%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous sodium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 100℃; for 3h; Inert atmosphere;	7-Fluoro-6-(4-(1-methylpiperidin-4-yl)phenyl)quinazolin-4(3H)-one (44) A mixture of 6-bromo-7-fluoroquinazolin-4(3H)-one (100 mg, 0.4 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (187 mg, 0.6 mmol), Pd(dppf)Cl2.DCM (67 mg, 0.08 mmol) and sodium carbonate (131 mg, 1.2 mmol) in dioxane:water (4:1, 4 mL) was degassed and re-suffused with nitrogen three times. The mixture was heated at 100°C for 3 hours. After cooling, the reaction mixture was filtered and concentrated, and the residue was purified by reverse phase HPLC, eluting with 0-80% ACN/water (0.035% TFA modifier). The product was dissolved in ethyl acetate and washed with saturated Na2CO3 and saturated brine, dried (MgSO4), filtered, and concentrated under reduced pressure to give the title compound (24 mg, 17%). 1H NMR (500 MHz, DMSO-d6) d ppm 8.17 (d, 1H) 8.15 (s, 1H) 7.55 (m, 3H) 7.40 (d, 2H) 2.88 (d, 2H) 2.21 (s, 3H) 1.98 (m, 2H) 1.78 (m,2H) 1.70 (m, 2H) one proton masked by solvent peak.

Reference： [1]Current Patent Assignee: DANA-FARBER CANCER INSTITUTE - WO2020/257632, 2020, A1 Location in patent: Page/Page column 62; 89; 91
[2]Azevedo, Seth C.; Beyett, Tyler S.; Bunnell, Thomas; Eck, Michael J.; Feru, Frederic; Gero, Thomas W.; Gokhale, Prafulla C.; Gray, Nathanael S.; Heppner, David E.; Jang, Jaebong; Li, Zhengnian; Scott, David A.; Shin, Bo Hee; Soroko, Kara M.; To, Ciric; Jänne, Pasi A. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 68]
[3]Azevedo, Seth C.; Beyett, Tyler S.; Bunnell, Thomas; Eck, Michael J.; Feru, Frederic; Gero, Thomas W.; Gokhale, Prafulla C.; Gray, Nathanael S.; Heppner, David E.; Jang, Jaebong; Li, Zhengnian; Scott, David A.; Shin, Bo Hee; Soroko, Kara M.; To, Ciric; Jänne, Pasi A. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 68]

21
[ 950577-02-3 ]
[ 1247000-92-5 ]
2-(6-(3-fluoro-4-(1-methylpiperidin-4-yl)phenyl)-4-oxoquinazolin-3(4H)-yl)-2-phenyl-N-(thiazol-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water; 1,4-dioxane / 3 h / 100 °C / Inert atmosphere 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 18 h / 60 °C

Reference： [1]Current Patent Assignee: DANA-FARBER CANCER INSTITUTE - WO2020/257632, 2020, A1

22
[ 811-98-3 ]
[ 950577-02-3 ]
6-bromo-7-(methoxy-d3)quinazolin-4-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: d⁽⁴⁾-methanol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 6-bromo-7-fluoroquinazolin-4-ol In tetrahydrofuran at 20℃;	14.1 Step 1: Preparation of 6-bromo-7-(methoxy-d3)quinazolin-4-ol NaH (960 mg, 40 mmol) was added to a solution of THF (20 mL) and CD3OD (2 mL) at 0°C. After stirring for 30 minutes, 6-bromo-7-fluoroquinazolin-4-ol (1 g, 4.11 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction was quenched with water and the pH was adjusted to 6-7. After concentration under reduced pressure, the crude product was purified with chromatography using DCM/MeOH=20/l to afford 6-bromo-7-(methoxy-d3)quinazolin-4-ol (700 mg, 2.7 mmol, 66.0%) as a white solid. LC/MS: 258.0 [M+H]+.
66%	Stage #1: d⁽⁴⁾-methanol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 6-bromo-7-fluoroquinazolin-4-ol In tetrahydrofuran at 20℃;	14.1 Step 1: Preparation of 6-bromo-7-(methoxy-d3)quinazolin-4-ol NaH (960 mg, 40 mmol) was added to a solution of THF (20 mL) and CD3OD (2 mL) at 0°C. After stirring for 30 minutes, 6-bromo-7-fluoroquinazolin-4-ol (1 g, 4.11 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction was quenched with water and the pH was adjusted to 6-7. After concentration under reduced pressure, the crude product was purified with chromatography using DCM/MeOH=20/l to afford 6-bromo-7-(methoxy-d3)quinazolin-4-ol (700 mg, 2.7 mmol, 66.0%) as a white solid. LC/MS: 258.0 [M+H]+.

Reference： [1]Current Patent Assignee: ACCUTAR BIOTECHNOLOGY INC - WO2021/231400, 2021, A1 Location in patent: Paragraph 197
[2]Current Patent Assignee: ACCUTAR BIOTECHNOLOGY INC - WO2021/231400, 2021, A1 Location in patent: Paragraph 197

23
[ 950577-02-3 ]
[ 1256955-27-7 ]