253176-94-2|N-Boc-3-(iodomethyl)azetidine| Ambeed

CAS No. :	253176-94-2
Formula :	C₉H₁₆INO₂
M.W :	297.13
SMILES Code :	O=C(N1CC(CI)C1)OC(C)(C)C
MDL No. :	MFCD09951816
InChI Key :	CJVGFEARJOREHI-UHFFFAOYSA-N
Pubchem ID :	53249943

Safety of [ 253176-94-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 253176-94-2 ]

* 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 [ 253176-94-2 ]

[ 253176-94-2 ] Synthesis Path-Downstream 1~54

1
[ 82938-50-9 ]
[ 253176-94-2 ]
[ 253176-95-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 3235 - 3238.
[2]Patent: US6335324,2002,B1 .Location in patent: Page column 207.

2
[ 142253-56-3 ]
[ 253176-94-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 3235 - 3238.
[2]Journal of the American Chemical Society,2019,vol. 141,p. 12464 - 12469.

3
[ 253176-94-2 ]
[ 253176-96-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 3235 - 3238.

4
[ 253176-94-2 ]
[ 253176-97-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 3235 - 3238.

5
3-bromomethyl-azetidine-1-carboxylic acid tert-butyl ester [ No CAS ]
[ 253176-94-2 ]

References: [1]Patent: US6335324,2002,B1 .Location in patent: Page column 207.

6
[ 3430-13-5 ]
[ 253176-94-2 ]
[ 1236861-96-3 ]

Yield	Reaction Conditions	Operation in experiment
		B. Preparation of [1-(t-butoxycarbonyl)azetidin-3-yl]methyl}(iodo)zinc (C71). Zinc powder (116.5 g, 1.78 mol) was suspended in dimethylacetamide (300 mL) under argon. A mixture of trimethylsilyl chloride and 1,2-dibromoethane (7:5 v/v, 34.5 mL) was added and the mixture was stirred for 20 mins. A solution of C70 (426.8 g, 1.437 mol) in dimethylacetamide (650 mL) was added under water cooling and the reaction mixture was stirred overnight. The concentration of the resulting solution of compound C71 was about 1 mol/L and this was used in the next step.; C. Preparation of t-butyl 3-[(6-methylpyridin-3-yl)methyl]azetidine-1-carboxylate (C72). 5-Bromo-2-methylpyridine (25 g, 0.145 mol) was dissolved in dimethylacetamide (150 mL) and the solution was degassed. To the solution was added tetrakis(triphenylphosphine)palladium(0) (5 g, 4.4 mmol), copper iodide (1.7 g, 8.7 mmol) and the 1 mol/L solution of compound C71 (170 mL) under an atmosphere of argon. The reaction mixture was stirred at 50 C. for 12 h; during this time, partial decomposition of the catalyst was observed and additional amounts of tetrakis(triphenylphosphine)palladium(0) (5 g, 4.4 mmol) and copper iodide (0.9 g, 4.7 mmol) were added. The reaction mixture was stirred at 50 C. for 48 h, cooled and poured into a mixture of a saturated aqueous solution of ammonium chloride (600 mL) and diethyl ether (600 mL). The resulting mixture was stirred for 30 mins and filtered through a layer of Celite to remove insoluble impurities. The organic layer was separated and the aqueous layer was extracted with diethyl ether (4*300 mL). The combined organic extracts were dried over anhydrous sodium sulfate and evaporated. The residue was purified by silica gel chromatography (Eluant: EtOAc) to afford compound C72. Yield: 27.9 g, 0.106 mol, 73%.

References: [1]Patent: US2010/190771,2010,A1 .Location in patent: Page/Page column 36.

7
[ 1422772-71-1 ]
[ 253176-94-2 ]
[ 1422772-90-4 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1677 - 1692.

8
[ 95-16-9 ]
[ 253176-94-2 ]
[ 1621696-72-7 ]

References: [1]European Journal of Medicinal Chemistry,2014,vol. 84,p. 382 - 394.

9
cis-3-fluoro-4-[4-(4-fluoro-3-methylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester [ No CAS ]
[ 253176-94-2 ]
cis-4-[1-(1-tert-butoxycarbonylazetidin-3-ylmethyl)-4-(4-fluoro-3-methylphenyl)-1H-imidazol-2-yl]-3-fluoropiperidine-1-carboxylic acid benzyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of racemic c/s-3-fluoro-4-[4-(4-fluoro-3-methyl-phenyl)-1 H-imidazol-2-yl]- piperidine-1 -carboxylic acid benzyl ester (1200.00 mg; 2.92 mmol; 1 .00 eq.) in DMF (12 ml), was added NaH (349.96 mg; 8.75 mmol; 3.00 eq.). After stirring at RT for 30 min, 3- lodomethyl-azetidine-1 -carboxylic acid tert-butyl ester (1 .13 ml; 5.25 mmol; 1 .80 eq.) was added dropwise. The reaction mixture was stirred at RT for 2 h. The reaction was quenched with saturated aqueous NH4CI solution and ether acetate was added (60 ml), washed with water, 5% NaHC03, then brine. The organic phase was dried andconcentrated. The residue was purified by prep HPLC to affold the title compound. LC- MS (M+H = 581 , obsd. = 581 ).

References: [1]Patent: WO2014/143612,2014,A1 .Location in patent: Page/Page column 37-38.

10
[ 253176-94-2 ]
cis-3-[2-[1-(6-amino-5-isopropylpyrimidin-4-yl)-3-fluoropiperidin-4-yl]-4-(4-fluoro-3-methylphenyl)-1H-imidazol-1-ylmethyl]azetidine-1-carboxylic acid tert-butyl ester [ No CAS ]

References: [1]Patent: WO2014/143612,2014,A1 .

11
[ 253176-94-2 ]
cis-3-[4-(4-fluoro-3-methylphenyl)-2-(cis-3-fluoropiperidin-4-yl)-1H-imidazol-1-ylmethyl]azetidine-1-carboxylic acid tert-butyl ester [ No CAS ]

References: [1]Patent: WO2014/143612,2014,A1 .

12
[ 892408-42-3 ]
[ 253176-94-2 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium iodide; In acetone; at 35℃; for 16h;	To a solution of 1.94 g of tert-butyl 3-[(tosyloxy)methyl]azetidin-1-carboxylate in 15.5 ml acetone were added 837 mg of lithium iodide and the reaction mixture was stirred for 16 hours at 35 C. After cooling, it was diluted with 200 ml ethyl acetate and the organic phase washed twice with 30 ml portions of water and once with 20 ml saturated sodium chloride solution. After drying over sodium sulphate and filtration, this was concentrated in vacuo. In this manner, 1.6 g of tert-butyl-3-(iodomethyl)azetidin-1-carboxylate were obtained, which was further reacted without purification.

References: [1]Patent: US2016/89364,2016,A1 .Location in patent: Page/Page column 111.

13
[ 850363-67-6 ]
[ 253176-94-2 ]
tert-butyl 3-[(5-bromo-4-methoxy-2H-indazol-2-yl)methyl]azetidin-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
263 mg		To a solution of 1.94 g of tert-butyl 3-[(tosyloxy)methyl]azetidin-1-carboxylate in 15.5 ml acetone were added 837 mg of lithium iodide and the reaction mixture was stirred for 16 hours at 35 C. After cooling, it was diluted with 200 ml ethyl acetate and the organic phase washed twice with 30 ml portions of water and once with 20 ml saturated sodium chloride solution. After drying over sodium sulphate and filtration, this was concentrated in vacuo. In this manner, 1.6 g of tert-butyl-3-(iodomethyl)azetidin-1-carboxylate were obtained, which was further reacted without purification. To a solution of 620 mg of 5-bromo-7-methoxy-1H-indazole in 24 ml DMF were added 1.11 g of potassium carbonate and the mixture stirred at 25 C. for 30 minutes. Then 1.25 g of the iodide prepared above was added and the reaction mixture stirred for 3 hours at 60 C. After cooling, it was diluted with 200 ml 1:1 tert-butyl methyl ether/hexane, washed once each with 20 ml portions of water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo and the crude product thus obtained purified by column chromatography on silica gel with a hexane/ethyl acetate gradient. Yield: 263 mg of the title compound. 1H-NMR (300 MHz, CDCl3): δ=1.43 (9H), 3.23 (1H), 3.78 (2H), 4.07 (2H), 4.10 (3H), 4.59 (2H), 7.28 (1H), 7.36 (1H), 8.03 (1H).

References: [1]Patent: US2016/89364,2016,A1 .Location in patent: Page/Page column 111.

14
[ 78299-75-9 ]
[ 253176-94-2 ]
tert-butyl 3-((5-(benzyloxy)-2H-indazol-2-yl)methyl)azetidine-1-carboxylate [ No CAS ]
tert-butyl 3-((5-(benzyloxy)-1H-indazol-1-yl)methyl)azetidine-1-carboxylate [ No CAS ]