[ CAS No. 943060-59-1 ]

Name: 943060-59-1|tert-Butyl azetidin-3-yl(methyl)carbamate hydrochloride|95%
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Quality Control of [ 943060-59-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 943060-59-1 ]

Product Details of [ 943060-59-1 ]

CAS No. :	943060-59-1	MDL No. :	MFCD12963843
Formula :	C₉H₁₉ClN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VASMJPUWUNCMPT-UHFFFAOYSA-N
M.W :	222.71	Pubchem ID :	53486267
Synonyms :

Calculated chemistry of [ 943060-59-1 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.89
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	61.55
TPSA :	41.57 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.72 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.32
Log Po/w (WLOGP) :	1.25
Log Po/w (MLOGP) :	0.86
Log Po/w (SILICOS-IT) :	0.19
Consensus Log Po/w :	0.72

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.79
Solubility :	3.63 mg/ml ; 0.0163 mol/l
Class :	Very soluble
Log S (Ali) :	-1.79
Solubility :	3.58 mg/ml ; 0.0161 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.16
Solubility :	15.6 mg/ml ; 0.0698 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.18

Safety of [ 943060-59-1 ]

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 [ 943060-59-1 ]

* 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.

Downstream synthetic route of [ 943060-59-1 ]

[ 943060-59-1 ] Synthesis Path-Downstream 1~39

1
[ 56-05-3 ]
[ 943060-59-1 ]
[ 854038-92-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine; In ethanol; at 20℃; for 2h;Heating / reflux;	Preparation 12 tert-Butyl [1-(2-amino-6-chloro-pyrimidin-4-yl)-azetidin-3-yl]-methyl-carbamate 2-Amino-4,6-dichloropyrimidine (26.2 g, 160 mmol) was added portionwise to a stirred solution of azetidin-3-methyl-carbamic acid tert-butyl ester HCI salt (37.4 g, 168 mmol) in absolute EtOH (400 mL) followed by TEA (55.6 mL, 400 mmol) dropwise at ambient temperature. The resulting suspension was warmed to reflux (initially a clear solution was observed on warming) which resulted in the gradual formation of a precipitate. The mixture was refluxed for a total of 2 hours. The mixture was allowed to cool and diluted with water (200 mL) dropwise over 30 min and stirring continued for 45 min. The resulting solid was filtered, washed with water (150 mL) and dried under suction to yield the title compound as a white solid (42.74 g, 85%). hu 1H NMR (400 MHz, CDCl3): delta 5.66 (1H, s), 5.02 (1H, br s), 4.86 (2H, br s), 4.20 (2H, t), 4.04 (2H, m), 2.91 (3H, s), 1.47 (9H, s) ppm. MS (APCI) m/z 314 [M+H]+

Reference： [1]Patent: US2007/185075,2007,A1 .Location in patent: Page/Page column 17

2
8-chlorotetrazolo[1,5-a]pyrazine [ No CAS ]
[ 943060-59-1 ]
[ 1334135-94-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In ethanol; at 25℃; for 1h;	A 2 L round bottom flask was charged with 8-chlorotetrazolo[l,5-a]pyrazine (100 g, 0.64 mol), triethylamine (195 g, 1.93 mol) and ethanol (1 L). To the above was added <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (146 g, 0.66 mol) at 25 C. The resulting mixture was stirred at 25 C for 1 h. Work-up: the resulting crystalline solid was collected by filtration, washed with ethanol (200 mL), and dried to afford 176 g (91 ) of the product as a white solid. MS m/z: 306(M+H+).
91%	With triethylamine; In ethanol; at 25℃; for 1h;	2 L round bottom flask was charged with 8-chlorotetrazolo[l,5-a]pyrazine (100 g, 0.64 mol), triethylamine (195 g, 1.93 mol) and ethanol (1 L). To the above was added <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (146 g, 0.66 mol) at 25 C. The resulting mixture was stirred at 25 C for 1 h. Work-up: the resulting crystalline solid was collected by filtration, washed with ethanol (200 mL), and dried to afford 176 g (91 ) of the product as a white solid. MS m/z: 306 (M+H+).

Reference： [1]Patent: WO2011/112766,2011,A2 .Location in patent: Page/Page column 88; 89
[2]Patent: WO2013/39785,2013,A2 .Location in patent: Page/Page column 84

3
[ 943060-59-1 ]
2,3-dichloro-7-(trifluoromethyl)pyrido[2,3-b]pyrazine [ No CAS ]
tert-butyl (1-(2-chloro-7-(trifluoromethyl)pyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	2,3-Dichloro-7-(trifluoromethyl)pyrido[2,3-b]pyrazine (100.0 mg, 0.37 mmol) and TEA (0.26 mL, 1.85 mmol) were dissolved in DCM (10.0 mL), and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (83.0 mg, 0.37 mmol) diluted in DCM (5.0 mL) and TEA (0.26 mL, 1.85 mmol) were slowly added thereto at 0 C. The reaction mixture was stirred at room temperature for one hour. The reaction mixture was poured into saturated NH4Cl aqueous solution and extracted with DCM (30.0 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and then distilled under reduced pressure. The residue was purified by column chromatography (DCM:MeOH=100:0) on amine silica. The fractions containing the product were collected and evaporated to obtain brown solid compound of tert-butyl (1-(2-chloro-7-(trifluoromethyl)pyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate. [0784] LCMS ESI (+): 418 (M+1)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 0783-0784

4
[ 943060-59-1 ]
2,3,7,8-tetrachloropyrido[2,3-b]pyrazine [ No CAS ]
tert-butyl methyl(1-(2,7,8-trichloropyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	2,3,7,8-Tetrachloropyrido[2,3-b]pyrazine (100.0 mg, 0.37 mmol) and TEA (0.3 mL, 1.85 mmol) were dissolved in DCM (8.0 mL), and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (83.0 mg, 0.37 mmol) diluted in DCM (2.0 mL) and TEA (0.3 mL, 1.85 mmol) were slowly added thereto at 0 C. The reaction mixture was stirred at room temperature for one hour and poured into saturated NH4Cl aqueous solution, and it was then extracted with DCM (30.0 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and distilled under reduced pressure. The residue was purified by column chromatography (DCM:MeOH=100:0) on amine silica. The fractions containing the product were collected and evaporated to obtain brown solid compound of tert-butyl methyl(1-(2,7,8-trichloropyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)carbamate. [0879] LCMS ESI (+): 418 (M+1), 420 (M+3)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 0878-0879

5
[ 943060-59-1 ]
2,3-dichloro-7-nitropyrido[2,3-b]pyrazine [ No CAS ]
tert-butyl (1-(2-chloro-7-nitropyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	2,3-Dichloro-7-nitropyrido[2,3-b]pyrazine (68.0 mg, 0.28 mmol) and tert-butyl azetidin-3-yl(methyl)carbamate HCl salt (61.8 mg, 0.28 mmol) were added to DCM (6.0 mL), and TEA (0.12 mL, 0.84 mmol) was slowly added thereto at 0 C. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. The residue was purified by column chromatography (n-Hex:EtOAc=70:30) on silica. The fractions containing the product were collected and evaporated to obtain white solid compound of tert-butyl (1-(2-chloro-7-nitropyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate (95.0 mg, 87%). [1190] LCMS ESI (+): 395 (M+1)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1189-1190

6
[ 943060-59-1 ]
2-bromo-6-chloropyrido[2,3-e]pyrrolo[1,2-a]pyrazine [ No CAS ]
tert-butyl (1-(2-bromopyrido[2,3-e]pyrrolo[1,2-a]pyrazin-6-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
179.0 mg	With triethylamine; In N,N-dimethyl acetamide; at 110℃; for 12h;	2-Bromopyrido[2,3-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (178.0 mg, 0.67 mmol) was dissolved in POCl3 (3.0 mL), and then DIPEA (141.0 muL, 0.81 mmol) was added thereto. The reaction mixture was stirred at 120 C. for 12 hours, cooled to room temperature and then concentrated under reduced pressure. Unpurified 2-bromo-6-chloropyrido[2,3-e]pyrrolo[1,2-a]pyrazine and TEA (0.5 mL, 3.35 mmol) were dissolved in DMA (7.0 mL), and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (164.0 mg, 0.74 mmol) was added thereto. The reaction mixture was stirred at 110 C. for 12 hours, cooled to room temperature and then concentrated under reduced pressure. The residue was purified by column chromatography (DCM:MeOH=97:3) on amine silica. The fractions containing the product were collected and concentrated to obtain brown solid compound of tert-butyl (1-(2-bromopyrido[2,3-e]pyrrolo[1,2-a]pyrazin-6-yl)azetidin-3-yl)(methyl)carbamate (179.0 mg, 62% in 2 steps). [1215] LCMS ESI (+): 432 (M+1), 434 (M+3)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1214-1215

7
[ 943060-59-1 ]
2,6-dichloropyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine [ No CAS ]
tert-butyl (1-(2-chloropyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazin-6-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 0.5h;	2,6-Dichloropyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine (35.0 mg, 0.12 mmol) and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (41.0 mg, 0.18 mmol) were added to DCM (1.0 mL), and TEA (51.0 muL, 0.37 mmol) was slowly added thereto at room temperature. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. The residue was purified column chromatography (n-Hex:EtOAc=70:30) on silica. The fractions containing the product were collected and concentrated to obtain yellow solid compound of tert-butyl (1-(2-chloropyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazin-6-yl)azetidin-3-yl)(methyl)carbamate. TFA (0.4 mL) was added to a mixture of tert-butyl (1-(2-chloropyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazin-6-yl)azetidin-3-yl)(methyl)carbamate and DCM (1.0 mL), and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (MeOH:DCM=5:95) on amine silica. The fractions containing the product were collected and concentrated to obtain beige solid compound of 1-(2-chloropyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazin-6-yl)-N-methylazetidin-3-amine (30.0 mg, 86% in 2 steps).

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1230-1232

8
[ 943060-59-1 ]
4,8-dichloropyrido[3,4-e][1,2,4]triazolo[4,3-a]pyrazine [ No CAS ]
tert-butyl (1-(8-chloropyrido[3,4-e][1,2,4]triazolo[4,3-a]pyrazin-4-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 1h;	4,8-Dichloropyrido[3,4-e][1,2,4]triazolo[4,3-a]pyrazine (3.5 mg, 0.01 mmol) and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (4.1 mg, 0.02 mmol) were added to DCM (0.2 mL), and TEA (5.0 muL, 0.04 mmol) was added thereto at room temperature. The reaction mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure to obtain tert-butyl (1-(8-chloropyrido[3,4-e][1,2,4]triazolo[4,3-a]pyrazin-4-yl)azetidin-3-yl)(methyl)carbamate. TFA (0.2 mL) was added to a mixture of unpurified tert-butyl (1-(8-chloropyrido[3,4-e][1,2,4]triazolo[4,3-a]pyrazin-4-yl)azetidin-3-yl)(methyl)carbamate and DCM (1.0 mL), and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography (MeOH:DCM=5:95) on amine silica. The fractions containing the product were collected and concentrated to obtain beige solid compound of 1-(8-chloropyrido[3,4-e][1,2,4]triazolo[4,3-a]pyrazin-4-yl)-N-methylazetidin-3-amine (2.0 mg, 57% in 2 steps).

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1243-1245

9
[ 943060-59-1 ]
C₁₀H₅BrClN₃ [ No CAS ]
tert-butyl (1-(2-bromopyrido[3,2-e]pyrrolo[1,2-c]pyrimidin-6-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28.0 mg	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 12h;	DIPEA (24.0 muL, 0.14 mmol) was added to suspension of 2-bromopyrido[3,2-e]pyrrolo[1,2-c]pyrimidin-6-ol (30.0 mg, 0.11 mmol) and POCl3 (1.1 mL), and it was then stirred at 120 C. for 20 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The residue was dissolved in DCM (1.1 mL), and tert-butyl azetidin-3-yl(methyl)carbamate HCl salt (50.0 mg, 0.23 mmol) and DIPEA (200.0 muL, 1.13 mmol) were added thereto. The mixture was stirred at room temperature for 12 hours. The reaction mixture was purified by column chromatography (MeOH:DCM=1:50) on amine silica. The fractions containing the product were collected and evaporated to obtain yellow solid compound of tert-butyl (1-(2-bromopyrido[3,2-e]pyrrolo[1,2-c]pyrimidin-6-yl)azetidin-3-yl)(methyl)carbamate (28.0 mg, 57%). [1126] LCMS ESI (+): 433 (M+1), 435 (M+3) [1127] 1H-NMR (400 MHz, DMSO-d6); delta: 8.65 (d, 1H, J=1.8 Hz), 8.46 (d, 1H, J=1.8 Hz), 7.60 (m, 1H), 7.25 (m, 1H), 6.84 (m, 1H), 5.01-4.90 (m, 1H), 4.68 (m, 2H), 4.54 (m, 2H), 2.93 (s, 3H), 1.41 (s, 9H)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1125-1127

10
[ 943060-59-1 ]
C₁₀H₆BrClN₄ [ No CAS ]
tert-butyl (1-(9-bromo-2-methylpyrazolo[1,5-c]pyrido[3,2-e]pyrimidin-5-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32.0 mg	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 12h;	DIPEA (22.0 muL, 0.13 mmol) was added to suspension of 9-bromo-2-methylpyrazolo[1,5-c]pyrido[3,2-e]pyrimidin-5-ol (30.0 mg, 0.11 mmol) and POCl3 (2.0 mL), and it was stirred at 120 C. for 20 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The residue was dissolved in DCM (1.0 mL). tert-Butyl azetidin-3-yl(methyl)carbamate HCl salt (119.0 mg, 0.54 mmol) and DIPEA (400.0 muL, 2.14 mmol) were added thereto. The mixture was then stirred at room temperature for 12 hours. The reaction mixture was purified by column chromatography (MeOH:DCM=1:50) on amine silica. The fractions containing the product were collected and evaporated to obtain yellow solid compound of tert-butyl (1-(9-bromo-2-methylpyrazolo[1,5-c]pyrido[3,2-e]pyrimidin-5-yl)azetidin-3-yl)(methyl)carbamate (32.0 mg, 67%). [1167] LCMS ESI (+): 448 (M+1), 450 (M+3) [1168] 1H-NMR (400 MHz, CDCl3); delta: 8.65 (m, 1H), 8.17 (m, 1H), 6.67 (s, 1H), 5.20-5.10 (m, 1H), 4.86 (m, 2H), 4.65 (m, 2H), 2.99 (s, 3H), 2.46 (m, 3H), 1.48 (s, 9H)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1166-1168

11
[ 943060-59-1 ]
C₉H₄BrClN₄ [ No CAS ]
tert-butyl (1-(9-bromopyrazolo[1,5-c]pyrido[3,2-e]pyrimidin-5-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32.0 mg	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 12h;	DIPEA (25.0 muL, 0.15 mmol) was added to suspension of 9-bromopyrazolo[1,5-c]pyrido[3,2-e]pyrimidin-5-ol (32.0 mg, 0.12 mmol) and POCl3 (2.0 mL), and it was stirred at 120 C. for 24 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The residue was dissolved in DCM (1.2 mL), and tert-butyl azetidin-3-yl(methyl)carbamate HCl salt (135.0 mg, 0.61 mmol) and DIPEA (420.0 muL, 2.42 mmol) were added thereto. The reaction mixture was stirred at room temperature for 12 hours and then purified by column chromatography (EtOAc:n-Hex=1:5) on amine silica. The fractions containing the product were collected and evaporated to obtain yellow solid compound of tert-butyl (1-(9-bromopyrazolo[1,5-c]pyrido[3,2-e]pyrimidin-5-yl)azetidin-3-yl)(methyl)carbamate (32.0 mg, 62%). [1177] LCMS ESI (+): 433 (M+1), 435 (M+3) [1178] 1H-NMR (400 MHz, CDCl3); delta: 8.68 (m, 1H), 8.24 (m, 1H), 7.97 (m, 1H), 6.89 (m, 1H), 5.20-5.10 (m, 1H), 4.89 (m, 2H), 4.68 (m, 2H), 2.99 (s, 3H), 1.48 (s, 9H)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1176-1178

12
[ 943060-59-1 ]
7-bromo-2,3-dichloro-8-methylpyrido[2,3-b]pyrazine [ No CAS ]
tert-butyl (1-(7-bromo-2-chloro-8-methylpyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; In dichloromethane; at 0℃; for 1h;	TEA (72.0 muL, 0.51 mmol) was added to the mixture of 7-bromo-2,3-dichloro-8-methylpyrido[2,3-b]pyrazine (50.0 mg, 0.17 mmol), <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (40.0 mg, 0.18 mmol) and DCM (1.7 mL) at 0 C. and stirred for one hour. The reaction mixture was purified by column chromatography (EtOAc:n-Hex=1:5) on silica. The fractions containing the product were collected and evaporated to obtain yellow solid compound of tert-butyl (1-(7-bromo-2-chloro-8-methylpyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate (58.0 mg, 76%). [0852] LCMS ESI(+): 442 (M+1), 444 (M+3) [0853] 1H-NMR (300 MHz, DMSO-d6); delta: 8.85 (s, 1H), 4.86 (m, 1H), 4.65-4.55 (m, 2H), 4.49-4.40 (m, 2H), 2.90 (s, 3H), 2.66 (s, 3H), 1.41 (s, 9H)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 0851-0853

13
[ 943060-59-1 ]
4,8-dichloro-2-methyloxazolo[4,5-c][1,8]naphthyridine [ No CAS ]
tert-butyl (1-(8-chloro-2-methyloxazolo[4,5-c][1,8]naphthyridine-4-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With triethylamine; In N,N-dimethyl-formamide; for 6h;	DMF (2.0 mL) was added to 4,8-Dichloro-2-methyloxazolo[4,5-c][1,8]naphthylidine (19.4 mg, 0.08 mmol), and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (26.0 mg, 0.12 mmol) and TEA (30.0 muL, 0.23 mmol) were then added thereto. The reaction mixture was stirred for 6 hours and distilled under reduced pressure. The residue was purified by column chromatography (EtOAc:n-Hex=1:2) on silica. The fractions containing the product were collected and evaporated to obtain pale yellow solid compound of tert-butyl (1-(8-chloro-2-methyloxazolo[4,5-c][1,8]naphthylidine-4-yl)azetidin-3-yl)(methyl)carbamate (30.0 mg, 97%). [1045] LCMS ESI (+): 404 (M+1) [1046] 1H-NMR (300 MHz, CDCl3); delta: 8.73 (d, 1H, J=2.7 Hz), 8.19 (d, 1H, J=2.7 Hz), 5.41-4.91 (m, 1H), 4.82-4.68 (m, 2H), 4.59-4.47 (m, 2H), 2.99 (s, 3H), 2.71 (s, 3H), 1.48 (s, 9H)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1044-1046

14
[ 943060-59-1 ]
4,8-dichloro-2-methylpyrido[2,3-e][1,2,4]triazolo[1,5-a]pyrazine [ No CAS ]
tert-butyl (1-(8-chloro-2-methylpyrido[2,3-e][1,2,4]triazolo[1,5-a]pyrazin-4-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	4,8-Dichloro-2-methylpyrido[2,3-e][1,2,4]triazolo[1,5-a]pyrazine (10.0 mg, 0.04 mmol) and TFA (16.5 muL, 0.12 mmol) were dissolve in DMF (0.2 mL), and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (13.0 mg, 0.06 mmol) was added thereto. The reaction mixture was stirred at room temperature for 2 hours, then concentrated and purified by column chromatography (MeOH:DCM=5:95) on silica. The fractions containing the product were collected and evaporated to obtain white solid compound of tert-butyl (1-(8-chloro-2-methylpyrido[2,3-e][1,2,4]triazolo[1,5-a]pyrazin-4-yl)azetidin-3-yl)(methyl)carbamate. Unpurified tert-butyl (1-(8-chloro-2-methylpyrido[2,3-e][1,2,4]triazolo[1,5-a]pyrazin-4-yl)azetidin-3-yl)(methyl)carbamate was dissolved in DCM (1.0 mL), and TFA (0.4 mL) was added thereto. The reaction mixture was stirred at room temperature for one hour and then purified by column chromatography (MeOH:DCM=5:95) on amine silica. The fractions containing the product were collected and evaporated to obtain white solid compound of 1-(8-chloro-2-methylpyrido[2,3-e][1,2,4]triazolo[1,5-a]pyrazin-4-yl)-N-methylazetidin-3-amine (7.0 mg, 45%).

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1086-1088

15
[ 943060-59-1 ]
7-bromo-2,3-dichloro-6-methylpyrido[2,3-b]pyrazine [ No CAS ]
tert-butyl (1-(7-bromo-2-chloro-6-methylpyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With triethylamine; In dichloromethane; at 0℃; for 1h;	TEA (140.0 muL, 1.02 mmol) was added to a mixture of 7-bromo-2,3-dichloro-6-methylpyrido[2,3-b]pyrazine (100.0 mg, 0.34 mmol), <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> salt (76.0 mg, 0.34 mmol) and DCM (3.4 mL) at 0 C., and it was then stirred for 1 hour. The reaction mixture was purified by column chromatography (EtOAc:n-Hex=1:4) on silica. The fractions containing the product were collected and evaporated to obtain red solid compound of tert-butyl (1-(7-bromo-2-chloro-6-methylpyrido[2,3-b]pyrazin-3-yl)azetidin-3-yl)(methyl)carbamate (43.0 mg, 28%). [1099] LCMS ESI (+): 442 (M+1), 444 (M+3) [1100] 1H-NMR (400 MHz, CDCl3); delta: 8.23 (s, 1H), 5.02-4.90 (m, 1H), 4.78-4.68 (m, 2H), 4.50-4.49 (m, 2H), 2.96 (s, 3H), 2.836 (s, 3H), 1.48 (s, 9H)

Reference： [1]Patent: US2014/315888,2014,A1 .Location in patent: Paragraph 1098-1100

16
[ 943060-59-1 ]
[ 138500-85-3 ]
methyl{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]azetidin-3-yl}carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With triethylamine; In tetrahydrofuran; at 20℃; for 18h;Inert atmosphere;	Methyl-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-azetidin-3-yl}-carbamic acid tert-butyl ester To 4-bromomethylboronic acid pinacol ester (500 mg, 168 mmol) and azetidin-3-yl-methyl-carbamic acid tert-butyl ester hydrochloride (561 mg, 2.52 mmol) in anhydrous THF (12 mL) was added NEt3 (704 mul, 5.05 mmol). The reaction mixture was stirred at RT, under N2 balloon, for 18 h. The reaction mixture was concentrated in vacuo, suspended in CH2Cl2 and washed with H2O. The aqueous layer was separated and washed with CH2Cl2. The organic layers were combined, dried (phase separation cartridge) and the solvent removed in vacuo. The crude material was purified by silica gel column chromatography eluting with CH2Cl2 and increasing the polarity to 20% MeOH/CH2Cl2 to afford methyl-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-azetidin-3-yl}-carbamic acid tert-butyl ester as a colourless oil (441 mg, 65%). AnalpH2_MeOH-4 min(3): Rt 2.21 min; m/z 403 [M+1]+.

Reference： [1]Patent: US2015/99732,2015,A1 .Location in patent: Paragraph 1474-1475

17
[ 943060-59-1 ]
ethyl (S)-2-(2-(3-bromo-1-methyl-1H-indazol-5-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-(tert-butoxy)acetate [ No CAS ]
ethyl (S)-2-(tert-butoxy)-2-(2-(3-(3-((tert-butoxycarbonyl)(methyl)amino)azetidin-1-yl)-1-methyl-1H-indazol-5-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; at 110℃; for 1h;Inert atmosphere; Microwave irradiation;	A microwave vial containing Tris(dibenzylideneacetone) dipalladium (0) (14.6 mg, 16 mumol), 2-(Dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl (7.6 mg, 16 mumol) and potassium phosphate tribasic (84.6 mg, 399 mumol) in 1,4-dioxane (1 mL) was purged with Argon for 5 min. Ethyl (S)-2-(2-(3-bromo-1-methyl-1H-indazol-5-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-(tert-butoxy)acetate (50 mg, 80 mumol) and <strong>[943060-59-1]tert-butyl azetidin-3-yl(methyl)carbamate hydrochloride</strong> (53 mg, 240 mumol). The mixture was sealed and reacted in a microwave reactor at 110 C. for 1 h. After cooling to room temperature, the resulting mixture was diluted ethyl acetate. The mixture was washed with brine. The organic phase was dried (Na2SO4) and concentrated. The residue was purified by CombiFlash (40 g, Gold, 0-50% EtOAc/Hex plus 0.1% TEA) to give desired product. LCMS-ESI+: calc'd for: C39H46ClN5O5S; 732.3 (M+H)+; found: 732.0 (M+H)+.

Reference： [1]Patent: US2018/118734,2018,A1 .Location in patent: Paragraph 0694; 0695

18
[ 943060-59-1 ]
2-(((5-fluoropyridin-3-yl)methyl)amino)thieno[3,2-d]pyrimidine-4-carboxylic acid [ No CAS ]
tert-butyl (1-(2-(((5-fluoropyridin-3-yl)methyl)amino)thieno[3,2-d]pyrimidine-4-carbonyl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃;	General procedure: To a solution of 2-[[(l,S)-l-(3- pyridyl)ethyl]amino]thieno[3,2-<i]pyrimidine-4-carboxylic acid dihydrochloride (37 mg, 0.1 mmol) in DMF (2 mL) were added (3R)-3-fluoropyrrolidine hydrochloride (19 mg, 0.15 mmol), HATU (57 mg, 0.15 mmol), and DIEA (87 uL, 0.5 mmol). The mixture thus obtained was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with 5% NaHCC , water, and brine, then dried over MgS04. The solvent was evaporated in vacuo and the residue was purified by flash chromatography on silica gel (12 g HP silica, Teledyne Isco) eluting with 10% to 50% solvent A (DCM/MeOH/NH4OH, 100/10/1) in DCM to provide ((R)-3-fluoropyrrolidin-l-yl)(2-(((5)-l-(pyridin-3- yl)ethyl)amino)thieno[3,2-<i]pyrimidin-4-yl)methanone (31 mg, 84% yield) as a light yellow solid. MR (400 MHz, CDCb) delta 1.64 (3H, d, J= 7.2 Hz), 1.99 (1H, m), 2.27 (1H, m), 3.60-3.86 (2H, m), 3.97-4.15 (2H, m), 4.43 (1H, m), 5.20 (1H, m), 5.43 (1H, d, J= 6.4 Hz), 7.18 (1H, d, J= 5.2 Hz), 7.25 (1H, m), 7.71 (1H, dt, J= 6.4, 1.6 Hz), 7.96 (1H, t, J= 6.0 Hz), 8.49 (1H, dd, J= 4.8, 1.6 Hz), 8.69 (1H, d, J= 1.6 Hz) ppm. LCMS m/z = 372.2 [M+H+].

Reference： [1]Patent: WO2019/46784,2019,A1 .Location in patent: Paragraph 0785; 0786; 1275; 1276

19
[ 943060-59-1 ]
N-(2,6-dibromopyrido[2,3-b]pyrazin-3-yl)-2-hydroxyacetamide [ No CAS ]
tert-butyl (1-(6-bromo-3-(2-hydroxyacetamido)pyrido[2,3-b]pyrazin-2-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2019/231270,2019,A1 .Location in patent: Paragraph 787; 808-812

20
[ 943060-59-1 ]
[ 2379-60-4 ]
tert-butyl (1-(3-chloro-6-nitroquinoxalin-2-yl)azetidin-3-yl)(methyl)carbamate [ No CAS ]