[ CAS No. 1064194-10-0 ] {[proInfo.proName]}

Name: 1064194-10-0|tert-Butyl 3-bromoazetidine-1-carboxylate|97%
Brand: Ambeed
SKU: A148938
Price: 5.0 USD
Availability: InStock
Rating: 90 (35 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 1064194-10-0

Structure of 1064194-10-0 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1064194-10-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1064194-10-0 ]

SDS Specification

Alternatived Products of [ 1064194-10-0 ]

Product Details of [ 1064194-10-0 ]

CAS No. :	1064194-10-0	MDL No. :	MFCD16658899
Formula :	C₈H₁₄BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RUTPPPNQDPSSBM-UHFFFAOYSA-N
M.W :	236.11	Pubchem ID :	53415291
Synonyms :

Calculated chemistry of [ 1064194-10-0 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.88
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	54.85
TPSA :	29.54 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) :	-6.53 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.63
Log Po/w (XLOGP3) :	1.71
Log Po/w (WLOGP) :	1.62
Log Po/w (MLOGP) :	1.56
Log Po/w (SILICOS-IT) :	1.15
Consensus Log Po/w :	1.73

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.18
Solubility :	1.55 mg/ml ; 0.00656 mol/l
Class :	Soluble
Log S (Ali) :	-1.95
Solubility :	2.67 mg/ml ; 0.0113 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.57
Solubility :	6.28 mg/ml ; 0.0266 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.29

Safety of [ 1064194-10-0 ]

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 [ 1064194-10-0 ]

* 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 [ 1064194-10-0 ]
Downstream synthetic route of [ 1064194-10-0 ]

[ 1064194-10-0 ] Synthesis Path-Upstream 1~3

1
[ 19540-05-7 ]
[ 24424-99-5 ]
[ 1064194-10-0 ]

Yield	Reaction Conditions	Operation in experiment
2.21 g	With lithium bromide In tetrahydrofuran; dibutyl ether; acetonitrile at -78 - 24℃;	To a flame-dried 500 mL round bottom flask was added 1-amino-2,3-dibromopropane hydrobromide (17) (3.5 g, 11.8 mmol, 1 equiv.) and stirred without solvent toobtain 17 as a fine powder under argon (alternatively, crystals of 17 could be ground to a fine powder by handbefore use). Dry THF (35 mL) was added to the flask and cooled to –78 oC. PhLi solution (1.8M in dibutyl ether,18.5 mL, 35.3 mmol, 3 equiv.) was slowly added via syringe and the reaction mixture stirred at –78 oC for 2 h.To the resulting mixture was added MeCN (112 mL), LiBr (4.2 g, 35.3 mmol, 3 equiv.) and Boc2O (5.4 mL, 23.6mmol, 2 equiv.) at –78 oC and warmed to rt overnight. The resulting mixture was poured into water (200 mL),washed with sat. aq. Na2S2O3 (50 mL) and then extracted with diethyl ether (3 x 150 mL). The combinedorganic layers were washed with brine (50 mL), dried over Na2SO4, and concentrated. The crude material waspurified by flash chromatography (silica gel, 5–20percent EtOAc in hexanes) to give the desired product 20 (2.21 g,79percent). Physical State: clear liquid; Rf = 0.38 (1:9 EtOAc/hexanes, vis. KMnO4); 1H NMR (500 MHz, CDCl3): δ 4.55– 4.46 (m, 3H), 4.22 – 4.14 (m, 2H), 1.44 (s, 9H); 13C NMR (126 MHz, CDCl3): δ 155.8, 80.2, 60.3 (br, 2C), 33.0,28.4 (3C); All spectral data are in accordance with the previously reported literature values.14

Reference： [1] Arkivoc, 2018, vol. 2018, # 4, p. 195 - 214

2
[ 141699-58-3 ]
[ 1064194-10-0 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 23, p. 6160 - 6163

3
[ 141699-55-0 ]
[ 1064194-10-0 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 23, p. 6160 - 6163

[ 1064194-10-0 ] Synthesis Path-Downstream 1~65

1
[ 74115-13-2 ]
[ 1064194-10-0 ]
[ 1374144-65-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;	To a solution of 5-bromopyridin-3-ol (0.285 g, 1.64 mmol) in DMF (2.5 mL) was added K2CO3 (0.453 g, 3.28 mmol), followed by <strong>[1064194-10-0]3-bromo-azetidine-1-carboxylic acid tert-butyl ester</strong> (0.425 g, 1.8 mmol) in DMF (0.5 mL) and the reaction mixture was heated to 60° C. and stirred over night. The reaction mixture was diluted with EtOAc, poured into sat. NaHCO3 solution (10 mL) and the aqueous layer was extracted EtOAc (2×20 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 50percent EtOAc-heptane gradient to give the title compound (0.539 g, 100percent) as a colorless crystalline solid. MS: 329.1 (M+H+).
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;	Intermediate A-283-(5-Bromopyridin-3-yloxy)-azetidine-l-carboxylic acid tert-butyl esterTo a solution of 5-bromopyridin-3-ol (0.285 g, 1.64 mmol) in DMF (2.5 mL) was added K2CO3 (0.453 g, 3.28 mmol), followed by 3-bromo-azetidine-l-carboxylic acid tert-butyl ester (0.425 g, 1.8 mmol) in DMF (0.5 mL) and the reaction mixture was heated to 60 °C and stirred over night. The reaction mixture was diluted with EtOAc, poured into sat. NaHCC"3 solution (10 mL) and the aqueous layer was extracted EtOAc (2 x 20 mL).Combined organics were washed with brine, dried over Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 50percent EtO Ac-heptane gradient to give the title compound (0.539 g, 100percent) as a colorless crystalline solid. MS: 329.1 (M+H+).

Reference： [1]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0636; 0637
[2]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 96

2
[ 5332-24-1 ]
[ 1064194-10-0 ]
[ 1612156-09-8 ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 5771 - 5780

3
[ 1064194-10-0 ]
[ 182344-70-3 ]
[ 1612156-17-8 ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5
[2]Journal of Organic Chemistry,2014,vol. 79,p. 5771 - 5780

4
[ 104-92-7 ]
[ 1064194-10-0 ]
[ 1510865-75-4 ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 5771 - 5780

5
[ 141699-58-3 ]
[ 1064194-10-0 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 6160 - 6163

6
[ 141699-55-0 ]
[ 1064194-10-0 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 6160 - 6163

7
[ 1064194-10-0 ]
4-(4-phenoxyphenoxy)-5H-pyrrolo[3,2-d]pyrimidine [ No CAS ]
tert-butyl 3-(4-(4-phenoxyphenoxy)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium t-butanolate; In N,N-dimethyl-formamide; at 100℃; for 48.0h;	Into a 20-mL vial was placed 4-(4-phenoxyphenoxy)-5H-pyrrolo[3,2-d]pyrimidine (600.00 mg; 1.98 mmol), tert-butyl 3-bromoazetidine- l-carboxylate (934.10 mg, 3.96 mmol), and sodium tert-butoxide (760.42 mg, 7.91 mmol) suspended in DMF (8.00 ml). The reaction mixture was heated to 100 °C for 2 days. The reaction mixture was purified using flash column chromatography. Fractions containing the desired product were combined and concentrated under reduced pressured. The product was then lyophilized overnight to afford tert-butyl 3-(4-(4- phenoxyphenoxy)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)azetidine-l-carboxylate (918.00 mg, 100percent yield) as a yellow, viscous liquid. MS: m/z = 459 [M+H]+.

Reference： [1]Patent: WO2015/17502,2015,A1 .Location in patent: Paragraph 00232; 00238

8
[ 623-12-1 ]
[ 1064194-10-0 ]
[ 1510865-75-4 ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5

9
[ 14548-38-0 ]
[ 1064194-10-0 ]
tert-butyl 3-(3-oxo-2,3-dihydro-1H-inden-5-yl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5

10
[ 623-03-0 ]
[ 1064194-10-0 ]
tert-butyl-3-(4-cyanophenyl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5

11
[ 1064194-10-0 ]
[ 52334-81-3 ]
tert-butyl 3-(5-(trifluoromethyl)pyridin-2-yl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5

12
[ 1064194-10-0 ]
1-benzyl-3-chloro-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
tert-butyl 3-(1-benzyl-1H-pyrrolo[2,3-b]pyridin-3-yl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5

13
[ 1064194-10-0 ]
3-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine [ No CAS ]
tert-butyl 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5

14
[ 766-51-8 ]
[ 1064194-10-0 ]
tert-butyl 3-(2-methoxyphenyl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 1849 - 1853
Angew. Chem.,2016,vol. 128,p. 1881 - 1885,5

15
[ 619-42-1 ]
[ 1064194-10-0 ]
[ 1240970-70-0 ]

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 8084 - 8087

Yield	Reaction Conditions	Operation in experiment
26%	With tetra-N-butylammonium tribromide; dibromoisocyanuric acid; In dichloromethane; at 20℃; for 3.0h;UV-irradiation;	General procedure: EXAMPLE 12 (0564) Bromodecarboxylation of alkanoic acids (0565) bromoisocyanurate (0566) RC02H -1 · RBr (0567) hv (0568) [00169] A mixture of alkanoic acid RC02H (2 mmol), bromoisocyanurate, additive (optionally) and solvent (12 mL) was stirred under fluorescent room light irradiation (FL). The reaction mixture washed with 1 M aq Na2S03, dried over Na2S04, filtered through short silica gel pad and concentrated in vacuo to yield crude alkyl bromide RBr. Optionally, the crude bromide was purified by chromatography on silica gel. The results are presented in Table 11.

17
[ 1064194-10-0 ]
1-(2,2-diethoxyethyl)-7-hydroxy-1,2-dihydroquinolin-2-one [ No CAS ]
tert-butyl 3-[1-(2,2-diethoxyethyl)-2-oxo-1,2-dihydroquinolin-7-yl]oxy}azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 90℃; for 17.0h;Inert atmosphere;	1-(2,2-diethoxyethyl)-7-hydroxy-1 ,2-dihydroquinolin-2-one 9d (0.20 g, 0.72 mmol) , tert- butyl 3-bromoazetidine-1-carboxylate (0.34 g, 1.44 mmol) and K2CO3 (0.30 g, 2.16 mmol) were mixed with NMP (3 mL) and heated to 90 °C for 17 h under nitrogen. The reaction mixture was allowed to cool to room temperature, partitioned between EtOAc (50 mL) and H2O (50 mL) and the organic phase separated. The aqueous phase was further extracted with EtOAc (2 x 50 mL) and the extracts combined with the original organic layer and concentrated under reduced pressure to give a residue. The residue was partitioned between Et20 (30 mL) and H2O (30 mL) and the layers separated. The organic layer was further washed with H2O (2 x 30 mL), brine (30 mL) and concentrated under reduced pressure. The residue was dissolved in DCM and H2O and passed through a SPE phase separator. The DCM filtrate was collected and concentrated under reduced pressure to give a clear oil. Purification via silica gel chromatography using 0-100percent EtOAc /pet ether gave tert-butyl 3-[1-(2,2-diethoxyethyl)-2-oxo-1 ,2-dihydroquinolin-7-yl]oxy}azetidine-1- carboxylate 103a (210.0 mg, 67percent) as a white gum. LC-MS (Method A) 387.2 [M-OEt]+, RT 3.32 min

Reference： [1]Patent: WO2017/137744,2017,A1 .Location in patent: Page/Page column 223

18
[ 1064194-10-0 ]
tert-butyl 3-[2-oxo-1-(2-oxoethyl)-1,2-dihydroquinolin-7-yl]oxy}azetidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2017/137744,2017,A1

19
[ 1064194-10-0 ]
tert-butyl 3-[1-(2-[(3aS,6S,7aS)-2-oxo-3-{3-oxo-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-6-yl}octahydro-1,3-benzoxazol-6-yl]amino}ethyl)-2-oxo-1,2-dihydroquinolin-7-yl]oxy}azetidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2017/137744,2017,A1

20
[ 371-42-6 ]
[ 1064194-10-0 ]
tert-butyl 3-[(4-fluorophenyl)thio]azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 1601 - 1605
Angew. Chem.,2018,vol. 130,p. 1617 - 1621,5

21
[ 1064194-10-0 ]
tert-butyl 3-((4-(3-(((methylsulfonyl)oxy)methyl)azetidin-1-yl)phenyl)sulfonyl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 1601 - 1605
Angew. Chem.,2018,vol. 130,p. 1617 - 1621,5

22
[ 1064194-10-0 ]
C₃₈H₅₀FN₅O₆S [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 1601 - 1605
Angew. Chem.,2018,vol. 130,p. 1617 - 1621,5

23
[ 1064194-10-0 ]
C₁₄H₁₈FNO₄S [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 1601 - 1605
Angew. Chem.,2018,vol. 130,p. 1617 - 1621,5

24
[ 1064194-10-0 ]
C₁₈H₂₆N₂O₅S [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 1601 - 1605
Angew. Chem.,2018,vol. 130,p. 1617 - 1621,5

25
[ 1064194-10-0 ]
C₃₈H₅₀FN₅O₆S [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 1601 - 1605
Angew. Chem.,2018,vol. 130,p. 1617 - 1621,5

26
[ 1064194-10-0 ]
[ 6188-23-4 ]
3-imidazo[1,2-a]pyridine-6-yl-azetidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.85 g	With pyridine; nickel(II) iodide; 4,4'-di-tert-butyl-2,2'-bipyridine; magnesium chloride; zinc; In N,N-dimethyl acetamide; at 65℃; for 16.0h;Sealed tube;	6-Bromo-imidazo[1,2-a]pyridine (1.0 g, 0.005 mol) was charged in a microwave vial and to this is added 4,4?-di-tert-butyl-2,2?-biprydine (0.14 g, 0.001 mol), <strong>[1064194-10-0]3-bromo-azetidine-1-carboxylic acid tert-butyl ester</strong> (1.2 g, 0.005 mol), zinc powder (0.66 g, 0.01 mol), NiI2 (0.16 g, 0.001 mol) and MgCl2 (0.48, 0.005 mol). To this is added pyridine (0.4 g, 0.005 mol) and DMA (15 mL). The reaction was closed and heated at 65° C. for 16 h. The mixture is cooled to RT, diluted with EtOAc and washed with satd NaHCO3 and brine. The organic layer is concentrated and the residue purified by silica gel chromatography (0-100percent EtOAc in heptans, followed by 5percent MeOH in DCM) to give the crude product which was subsequently purified by prep-HPLC to give 3-imidazo[1,2-a]pyridine-6-yl-azetidine-1-carboxylic acid tert-butyl ester (0.85 g, 3.1 mmol).

Reference： [1]Patent: US2018/72717,2018,A1 .Location in patent: Paragraph 0487

27
[ 1064194-10-0 ]
3-(3-bromoimidazo[1,2-a]pyridine-6-yl)azetidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: US2018/72717,2018,A1

28
[ 1064194-10-0 ]
3-{3-[4-(5-cyclopropylcarbamoyl-4-fluoro-2-methylphenyl)pyrazol-1-yl]imidazo[1,2-a]pyridine-6-yl}azetidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: US2018/72717,2018,A1

29
[ 19540-05-7 ]
[ 24424-99-5 ]
[ 1064194-10-0 ]

Yield	Reaction Conditions	Operation in experiment
2.21 g	With lithium bromide; In tetrahydrofuran; dibutyl ether; acetonitrile; at -78 - 24℃;	To a flame-dried 500 mL round bottom flask was added 1-amino-2,3-dibromopropane hydrobromide (17) (3.5 g, 11.8 mmol, 1 equiv.) and stirred without solvent toobtain 17 as a fine powder under argon (alternatively, crystals of 17 could be ground to a fine powder by handbefore use). Dry THF (35 mL) was added to the flask and cooled to ?78 oC. PhLi solution (1.8M in dibutyl ether,18.5 mL, 35.3 mmol, 3 equiv.) was slowly added via syringe and the reaction mixture stirred at ?78 oC for 2 h.To the resulting mixture was added MeCN (112 mL), LiBr (4.2 g, 35.3 mmol, 3 equiv.) and Boc2O (5.4 mL, 23.6mmol, 2 equiv.) at ?78 oC and warmed to rt overnight. The resulting mixture was poured into water (200 mL),washed with sat. aq. Na2S2O3 (50 mL) and then extracted with diethyl ether (3 x 150 mL). The combinedorganic layers were washed with brine (50 mL), dried over Na2SO4, and concentrated. The crude material waspurified by flash chromatography (silica gel, 5?20percent EtOAc in hexanes) to give the desired product 20 (2.21 g,79percent). Physical State: clear liquid; Rf = 0.38 (1:9 EtOAc/hexanes, vis. KMnO4); 1H NMR (500 MHz, CDCl3): delta 4.55? 4.46 (m, 3H), 4.22 ? 4.14 (m, 2H), 1.44 (s, 9H); 13C NMR (126 MHz, CDCl3): delta 155.8, 80.2, 60.3 (br, 2C), 33.0,28.4 (3C); All spectral data are in accordance with the previously reported literature values.14

Reference： [1]Arkivoc,2018,vol. 2018,p. 195 - 214

30
[ 1064194-10-0 ]
N-[3-(4-bromophenyl)-1,4-dimethyl-1H-pyrazol-5-yl]-6-(3,5-dimethyl-1H-pyrazol-1yl)pyrimidin-4-amine [ No CAS ]
tert-butyl 3-[4-(5-[6-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-yl]amino}-1,4-dimethyl-1H-pyrazol-3-yl)phenyl]azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With nickel(II) chloride ethylene glycol dimethyl ether complex; tris-(trimethylsilyl)silane; 4,4'-di-tert-butyl-2,2'-bipyridine; lithium hydroxide; In 1,2-dimethoxyethane; for 15.0h;Inert atmosphere;	In a microwave vial, (30.7 mg, 27.4 muiotaetaomicron), N-[3-(4-bromophenyl)-1,4-dimethyl-1H-pyrazol-5-yl]-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-amine (120 mg, 274 muiotaetaomicron), and lithium hydroxide (19.7 mg, 821 muiotaetaomicron) were loaded. DME (5.5 niL) was then added. The nickel pre-catalyst was then prepared in a second microwave vial. To this vial, nickel (II) chloride dimethoxyethane adduct (32.9 mg, 0.15 mmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (48.3 mg, 0.18 mmol) were loaded and dissolved in DME (12 mL), placed under argon, sealed and sonicated for 5 minutes. An aliquot of the nickel pre-catalyst solution just prepared (1.1 mL) was syringed into the vial containing the reactants. The solution was degassed a second time by sparging with argon while stirring for 10 minutes. Under a constant flow of argon, <strong>[1064194-10-0]tert-butyl 3-bromoazetidine-1-carboxylate</strong> (220 mu, 1.4 mmol) and 1,1,1, 3,3, 3-hexamethyl-2-(trimethylsilyl)trisilane (250 mu, 820 muiotaetaomicron) were then added to the reaction mixture using a Hamilton syringe. The microwave vial was then sealed with Parafilm, stirred and irradiated with two 34 W blue LED lamps (3 cm away) for 15 h. The reaction mixture was concentrated and the residue dissolved in acetonitrile/water and purified by preparative HPLC (column: Chromatorex C18; 125*30 mm, 10 muMu, flow 75 mL/min, gradient acetonitrile / water (containing 0.1percent trifluoroacetic acid) 30/70 to 95/5) to yield the desired product (60 mg, 86percent purity, 37percent> yield). LC-MS (method 10): Rt = 2.29 min; MS (ESIpos): m/z = 515 [M+H]+ 1H-NMR (400 MHz, dimethylsulfoxide-d6) delta [ppm]: -0.149 (0.20), -0.008 (1.57), 0.008 (1.69), 0.082 (0.66), 0.146 (0.28), 1.169 (0.21), 1.366 (0.34), 1.413 (16.00), 2.025 (4.55), 2.171 (1.11), 2.327 (0.34), 2.366 (0.30), 2.523 (0.88), 2.630 (4.10), 2.669 (0.38), 2.710 (0.31), 3.662 (3.05), 3.850 (0.73), 4.272 (0.49), 6.144 (0.81), 7.394 (0.98), 7.414 (1.14), 7.635 (0.23), 7.643 (0.20), 7.667 (0.89), 7.687 (0.71), 8.472 (0.26), 9.397 (0.59).

Reference： [1]Patent: WO2018/69222,2018,A1 .Location in patent: Page/Page column 589-590

31
[ 1064194-10-0 ]
C₃₀H₃₁N₃O₈ [ No CAS ]
C₃₈H₄₄N₄O₁₀ [ No CAS ]

Reference： [1]Patent: WO2018/149419,2018,A1 .Location in patent: Paragraph 001316

32
[ 1064194-10-0 ]
[ 344791-87-3 ]
(±) tert-butyl 3-(4-(4-methoxyphenyl)butan-2-yl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2018,vol. 140,p. 17433 - 17438

33
[ 1064194-10-0 ]
(4-bromopiperidin-1-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone [ No CAS ]
tert-butyl 3-(1-(6-(trifluoromethyl)nicotinoyl)piperidin-4-yl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2018,vol. 140,p. 17433 - 17438

34
[ 491-35-0 ]
[ 1064194-10-0 ]
[ 1180653-80-8 ]

Reference： [1]Chemical Science,2019,vol. 10,p. 976 - 982

35
[ 1064194-10-0 ]
(S)-8-bromo-N-(chroman-4-yl)-4-(dimethylamino)quinoline-3-carboxamide [ No CAS ]
tert-butyl (S)-3-(3-(chroman-4-ylcarbamoyl)-4-(dimethylamino)quinolin-8-yl)azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With (1,2-dimethoxyethane)dichloronickel(II); tris-(trimethylsilyl)silane; [4,4?-bis(1,1-dimethylethyl)-2,2?-bipyridine-N1,N1?]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; sodium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine; In 1,2-dimethoxyethane; for 18.0833h;Inert atmosphere; Irradiation; Cooling;	In a 20 mL vial a mixture of anhydrous sodium carbonate (99 mg, 0.938 mmol), (S)-8-bromo-N-(chroman-4-yl)-4-(dimethylamino)quinoline-3-carboxamide (200 mg, 0.469 mmol), tert-butyl 3-bromoazetidine- 1 -carboxylate (166 mg, 0.704 mmol), [4,4?-bis( 1,1 -dimethylethyl)-2,2?-bipyridine-Ni ,N1 ?]bis [3 ,5-difluoro-2- [5 -(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III)hexafluorophosphate (5 mg, 0.005 mmol) and tris(trimethylsilyl)silane (0.145 mL, 0.469 mmol) was degassed by purging with argon. 1 ,2-Dimethoxyethane (8.0 mL) (degassed by purging with nitrogen) was added. In an 8 mL screw capped vial a mixture of nickel(II) chloride ethylene glycol dimethyl ether complex (4 mg, 0.019 mmol) and 4,4?-di-tert-butyl-2,2?-dipyridyl (5 mg, 0.019 mmol) was degassed by purging with argon. 1 ,2-Dimethoxyethane (4.0 mL) (degassed by purging with nitrogen) was added.This mixture was gently warmed with a heat gun and was allowed to cool to room temperature while stirring for 5 mm. By syringe 2.0 mL of this nickel-catalyst containing solution was added to the reaction mixture. The resulting mixture was purged with argon for 5 mm and was subsequently stirred under irradiation with blue LED light for 18 h while cooling with a fan. Volatiles were removed in vacuo. Purification by reversed phase flash column chromatography (Method 5; 40 g) and preparativeHPLC (Method ii) afforded 51 mg (0.102 mmol; 21% of theory) of the title compound.LC-MS (Method 4): R = 4.04 mm; mlz = 503 (M+H)1H NMR (400 MHz, DMSO-d6) 9.09 (d, J= 8.2 Hz, 1H), 8.59 (s, 1H), 8.07 (d, J= 8.1 Hz, 1H), 7.70(d, J= 7.1 Hz, 1H), 7.54 (m, 1H), 7.36 (d, J= 7.0 Hz, 1H), 7.21 - 7.15 (m, 1H), 6.93 (m, 1H), 6.80 (d, J = 8.2 Hz, 1H), 5.29 - 5.22 (m, 1H), 4.58 (p, J= 7.8 Hz, 1H), 4.40 - 4.21 (m, 4H), 4.09 - 3.98 (m, 2H), 3.03 (s, 6H), 2.25 -2.16 (m, 1H), 2.09 -2.00 (m, 1H), 1.39 (s, 9H).

Reference： [1]Patent: WO2019/25341,2019,A1 .Location in patent: Page/Page column 141; 142

36
[ 1064194-10-0 ]
S-(trifluoromethyl)dimesitylsulfanium triflate [ No CAS ]
3-trifluoromethyl-azetidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 6853 - 6858

37
[ 1064194-10-0 ]
2-[2-bromo-5,8-dioxo-6-(propan-2-yl)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidin-4-yl]-N-(5-fluoropyridin-2-yl)acetamide [ No CAS ]
tert-butyl 3-[4-{2-[(5-fluoropyridin-2-yl)amino]-2-oxoethyl}-5,8-dioxo-6-(propan-2-yl)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidin-2-yl]azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With (1,2-dimethoxyethane)dichloronickel(II); tris-(trimethylsilyl)silane; [4,4?-bis(1,1-dimethylethyl)-2,2?-bipyridine-N1,N1?]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; lithium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine; at 35℃;Irradiation; Sealed tube; Inert atmosphere;	2-[2-bromo-5,8-dioxo-6-(propan-2-yl)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidin-4-yl]-N-(5-fluoropyridin-2-yl)acetamide (160 mg, 345 muetaiotaomicronIota) (example 75), 4,4'- bis(1,1-dimethylethyl)-2,2'-bipyridine-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate (7.75 mg, 6.91 muetaetaomicronIota), tris(trimethylsilyl)silane (1 10 muIota, 350 muetaetaomicronIota) and lithium carbonate (102 mg, 1.38 mmol) were dissolved in the reaction vial in benzotrifluoride (8.0 ml). In a separate vial, the nickel catalyst was prepared by dissolving nickel (II) chloride dimethoxyethane adduct (380 mug, 1.7 muetaetaomicronIota) and 4,4'-di-tert-butyl-2,2'- bipyridine (460 mug, 1.7 muetaetaomicronIota) in benzotrifluoride (100-fold amount in 10 mL) followed by stirring for 5 min. The catalyst solution (0,1 mL) was syringed to the sealed reaction vial and argon was bubbled through the solution for another 5 min then tert-butyl 3-bromoazetidine-1 - carboxylate (170 muIota, 1.0 mmol) was added. The reaction vial was placed in a water bath (to keep the temp, below 35 C) and was subsequently irradiated by two 40W Kessil LED Aquarium lamps. After quenching the reaction mixture with half saturated sodium bicarbonate solution and separated three times with ethyl acetate, dried over sodium sulfate and concentrated in vacuo. The crude was purified with preparative HPLC (Method F, gradient C, 60ml/min) to afford 96.5 mg (49% yield) of the title compound. LC-MS (Method H): Rt = 1.09 min; MS (ESIneg): m/z = 538 [M-H]" 1H NMR (400 MHz, DMSO-d6) delta [ppm]: 1.23 (d, 6H), 1.38 (s, 9H), 3.84-4.03 (m, 3H), 4.16-4.26 (m, 2H), 4.26-4.34 (m, 1H), 4.39 (s, 2H), 5.48 (br s, 2H), 6.69 (s, 1H), 7.64-7.77 (m, 1H), 8.00 (br d, 1H), 8.37 (d, 1H), 1 1.1 1 (s, 1H).

Reference： [1]Patent: WO2019/81343,2019,A1 .Location in patent: Page/Page column 378-379

38
[ 1064194-10-0 ]
tert-butyl 5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]
tert-butyl 5-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54.4%	With (1,2-dimethoxyethane)dichloronickel(II); tris-(trimethylsilyl)silane; [4,4?-bis(1,1-dimethylethyl)-2,2?-bipyridine-N1,N1?]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; sodium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine; In 1,4-dioxane; for 17.0h;Inert atmosphere; Sealed tube; Irradiation; Cooling;	A suspension of tert-butyl 5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (150 mg, 0.442 mmol), <strong>[1064194-10-0]tert-butyl 3-bromoazetidine-1-carboxylate</strong> (209 mg, 0.884 mmol), tris(trimethylsilyl)silane (165 mg, 0.663 mmol), [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 (1.24 mg, 1.11 mumol), and Na2CO3 (187 mg, 1.77 mmol) in 1,4-dioxane (3.5 mL) in a vial with a pressure-relief septum-lined cap and a stir bar was degassed with nitrogen gas for 5 minutes. To a separate vial was added nickel(II) chloride ethylene glycol dimethyl ether complex (7.29 mg, 0.033 mmol) and 4,4?-di-tert-butyl-2,2?-bipyridine (10.7 mg, 0.040 mmol), which was evacuated and backfilled with nitrogen gas followed by 1,4-dioxane (0.88 mL). This mixture was degassed with nitrogen gas for 10 minutes and stirred. The resulting solution containing the nickel complex was added to the suspension containing all other reagents, and then the resulting mixture was further degassed with nitrogen gas for another 10 minutes. The vessel was then sealed and placed in a rack with stirring and irradiation with 34 W Kessil KSH 150B blue grow lamps and a cooling fan for 17 hours. Upon completion, the reaction mixture was diluted with DCM, filtered, and concentrated. The crude material was taken up in hexanes with a trace of DCM for solubility and purified by silica gel column chromatography on a Teledyne Isco instrument eluting with Hex/DCM 0-100percent, then Hex/EtOAc 0-50percent to afford tert-butyl 5-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (100 mg, 0.241 mmol, 54.4percent yield). LCMS retention time 1.04 [TS]. MS (E+) m/z: 416.3 (M+H). This reaction was repeated several times to obtain larger quantities of material.

Reference： [1]Patent: US2019/185469,2019,A1 .Location in patent: Paragraph 0767-0768

39
[ 1008-89-5 ]
[ 1064194-10-0 ]
tert-butyl 3-(2-(pyridin-2-yl)phenyl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 9826 - 9830
Angew. Chem.,2019,vol. 131,p. 9931 - 9935,5

40
[ 103-16-2 ]
[ 1064194-10-0 ]
tert-butyl 3-(4-(benzyloxy)phenoxy)azetidine-1-carboxylate [ No CAS ]