Name: 1350821-95-2|Methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate|98%
Brand: Ambeed
SKU: A602274
Price: 50.0 USD
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1
[ 1350821-95-2 ]
[ 1350822-05-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine / dichloromethane / -10 - 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride; <i>tert</i>-butyl alcohol / acetonitrile / 1.5 h / 70 °C
0.047 g	With diethylamino-sulfur trifluoride In dichloromethane at -78 - 22℃; for 1h;	Intermediate A138B: Methyl 4-(fluoromethyl)bicyclo[2.2.1]heptane-1-carboxylate Intermediate A138B: Methyl 4-(fluoromethyl)bicyclo[2.2.1]heptane-1-carboxylate A solution of Intermediate A138A (0.155 g, 0.841 mmol) in DCM (5 mL), was cooled to -78° C. DAST (0.111 mL, 0.841 mmol) was added and the reaction mixture was stirred at 22° C. for 1 h. The reaction mixture was quenched at 0° C. by the careful addition of a saturated aq. solution of NaHCO3. The reaction mixture was diluted with DCM. The organic layer was separated and the aqueous phase was extracted twice more with DCM. The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. The crude reaction mixture was purified by silica gel chromatography (24 g REDISEP column, eluting with a gradient from 0-30% EtOAc in hexanes).

Reference： [1]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US9273058, 2016, B2 Location in patent: Page/Page column 657; 658

2
[ 1350821-95-2 ]
[ 1350821-85-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyridine / dichloromethane / -10 - 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride; <i>tert</i>-butyl alcohol / acetonitrile / 1.5 h / 70 °C 3: potassium hydroxide / methanol / Reflux

Reference： [1]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]

3
[ 1350821-95-2 ]
[ 1350821-89-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: pyridine / dichloromethane / -10 - 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride; <i>tert</i>-butyl alcohol / acetonitrile / 1.5 h / 70 °C 3: potassium hydroxide / methanol / Reflux 4: thionyl chloride / acetonitrile / 70 °C / Inert atmosphere 5: triethylamine / acetonitrile / 1 h / 20 °C

Reference： [1]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]

4
[ 1350821-95-2 ]
C₉H₁₂ClFO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: pyridine / dichloromethane / -10 - 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride; <i>tert</i>-butyl alcohol / acetonitrile / 1.5 h / 70 °C 3: potassium hydroxide / methanol / Reflux 4: thionyl chloride / acetonitrile / 70 °C / Inert atmosphere

Reference： [1]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]

5
[ 1350821-95-2 ]
C₃₅H₄₄F₂N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: pyridine / dichloromethane / -10 - 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride; <i>tert</i>-butyl alcohol / acetonitrile / 1.5 h / 70 °C 3: potassium hydroxide / methanol / Reflux 4: thionyl chloride / acetonitrile / 70 °C / Inert atmosphere 5: triethylamine / acetonitrile / 0.5 h / 20 °C

Reference： [1]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]

6
[ 1350821-95-2 ]
[ 1350821-94-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: pyridine / dichloromethane / -10 - 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride; <i>tert</i>-butyl alcohol / acetonitrile / 1.5 h / 70 °C 3: potassium hydroxide / methanol / Reflux 4: thionyl chloride / acetonitrile / 70 °C / Inert atmosphere 5: triethylamine / acetonitrile / 0.5 h / 20 °C 6: water; sodium hydrogencarbonate / methanol / 2 h / 50 °C

Reference： [1]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]

7
[ 358-23-6 ]
[ 1350821-95-2 ]
[ 1350821-98-5 ]

Yield	Reaction Conditions	Operation in experiment
77%	With pyridine In dichloromethane at -10 - 20℃; Inert atmosphere;	3. General procedure for synthesis of compounds 3a, 3c and 3d (LG = Triflate). General procedure: In a flame dried three-neck flask under argon atmosphere, alcohol 2 was dissolved in CH2Cl2 at room temperature. Pyridine was added to the solution via syringe and the reaction mixture was cooled to -10 oC with ice/ MeOH bath. Triflic anhydride was added dropwise to the reaction mixture in a way that the temperature remained below -2 oC. Upon completion of the addition, the reaction mixture was stirred for 1 hour at -10 oC, and thereafter was stirred further for 6-8 hours at room temperature, quenched with water and stirred for 15 minutes at room temperature. The organic phase was washed with 0.2 N HCl, water and brine. The organic phase was collected, dried (Na2SO4) and concentrated under vacuo to dryness.

Reference： [1]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]

8
[ 15448-76-7 ]
[ 1350821-95-2 ]

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5728 - 5735
[2]Patent: WO2014/142363,2014,A1
[3]Patent: US9273058,2016,B2

9
[ 15448-77-8 ]
[ 1350821-95-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With dimethylsulfide borane complex In tetrahydrofuran at 20℃;	1.D1.2 Step 2: Synthesis of methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate Under ice bath, In a single-neck flask containing 4-(carbomethoxy)bicyclo[2.2.1]heptane-1-carboxylic acid (4.17 g, 21.03 mmol), dry tetrahydrofuran (100 mL) was added. Borane dimethyl sulfide complex (2.7 mL, 27.35 mmol, 10.0 M) was slowly added dropwise using a syringe. After the dropwise addition was completed, the mixture was stirred at room temperature overnight. Methanol (10 mL) was added dropwise to the reaction solution, and the mixture was refluxed for 4 hours to quench. Ethyl acetate/water extraction, the organic phase was washed with water and saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, concentrated and separated by column chromatography (petroleum ether/ethyl acetate=3:2) to obtain methyl 4-(hydroxylmethyl)bicyclo[2.2.1]heptane-1-carboxylate (3.53 g, 90% yield).
89.12%	With dimethylsulfide borane complex In tetrahydrofuran at 20℃; for 16h;	8 Intermediate: Preparation of 4-(methoxymethyl)bicyclo[2.2.1]heptane-1-carbaldehyde I-8d Commercially available I-8d1 (60.00g, 302.70mmol, 1.0eq) was dissolved in THF (0.6L) and placed in a four-necked flask, under nitrogen protection, cooled to 0-10°C, BH 3-Me 2S was added dropwise (60.5mL, 2.0eq). During the dropwise addition, the temperature did not change significantly, but there was obvious outgassing. After dripping, the temperature was naturally raised to room temperature 20 °C, and the reaction was stirred overnight for 16 h. TLC showed complete reaction of starting material. Cool down to 0-10 °C, add saturated NH 4 Cl solution dropwise, and stir for 1 h after the dropping is completed. The system separated and the aqueous phase TLC monitored almost no product and was discarded. The organic phase was dried over magnesium sulfate and evaporated to dryness. After the crude product was separated by silica gel column chromatography (PE/EA(v/v)=20/110/1), a yellowish liquid I-8d2 (49.70 g, yield 89.12%) was obtained.
70%	Stage #1: 4-carbomethoxybicyclo<2.2.1>heptane-1-carboxylic acid With dimethylsulfide borane complex In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: With lithium hydroxide monohydrate In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;	2. General procedure for synthesis of compounds 2a-d. General procedure: In flame dried three-necked flask under argon atmosphere, the appropriate acid was dissolved in freshly distilled THF. This reaction mixture was cooled to 0 oC, 2 M borane dimethyl sulphide in THF was added dropwise and the reaction mixture was stirred at this temperature for 20 minutes then further stirred for 2.5 h at room temperature. This reaction mixture was quenched with water and stirred for 2 h at room temperature. The solvent was evaporated under reduced pressure and the residue was extracted with EtOAc. The organic layer was washed with saturated NaHCO3, collected, dried over anhydrous MgSO4 and evaporated in vacuo to dryness.

2.5 g	With borane-THF In tetrahydrofuran at -40 - 0℃;	228.E E) Methyl 4-(hydroxymethyl)bicyd [1269] ^ Borane-tetrahydrofuran complex (1 M THF solution, 22.7 mL) was added dropwise to a solution of 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-l-carboxylic acid (3.00 g) in THF (60 mL) at -40°C, the resultant was stirred for 1 hour at the same temperature, and was further stirred for 2 hours at 0°C. An aqueous saturated sodium hydrogen carbonate solution was added to the reaction mixture at 0°C, and extraction thereof was performed using ethyl acetate. The obtained organic layer was sequentially washed with water and a saturated saline solution, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure, thereby obtaining the title compound (2.50 g). 1H NMR (400 MHz, DMSO-d^ 1.21-1.24 (2H, m), 1.42 (2H, s), 1.55-1.61 (4H, m), 1.82-1.89 (2H, m), 3.42 (2H, d, J = 5.36 Hz), 3.58 (3H, s), 4.47 (1H, t, J = 5.36 Hz).
	With dimethylsulfide borane complex In tetrahydrofuran at 0 - 20℃; for 18h; Sealed tube; Inert atmosphere;	Intermediate A138A: Methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate Intermediate A138A: Methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate Intermediate A138A was prepared following the synthetic route described in Scheme 97. The experimental procedures described in Eur. J Med. Chem., 46:5728-5735 (2011) were followed. A flask charged with a solution of Intermediate A137D (316 mg, 1.594 mmol) in THF (8 mL) was sealed with a septum and purged with dry N2. The solution was cooled to 0° C. prior to the dropwise addition of a 2.0 M solution of borane-methyl sulfide complex (0.996 mL, 1.993 mmol) in THF. The reaction mixture was allowed to gradually warm to RT. After 18 h, MeOH (5 mL) was added to the reaction and the mixture was heated to reflux for 2 h. The solution was then cooled to RT, concentrated under reduced pressure and diluted with equal parts EtOAc and water. The organic phase was separated and the aqueous phase was extracted twice more with EtOAc. The combined organic layers were washed twice with a 1 N aq.
	With borane-THF In tetrahydrofuran at 25℃; for 2h; Inert atmosphere;	85.1 Step 1: 143-2 To a mixture of 143-1 (480 mg, 2.42 mmol) in THF (10 mL) was added Borane-tetrahydrofuran complex (1 M, 3.63 mL) at 0 under the nitrogen atmosphere dropwise. The reaction mixture was stirred for 2 hr at 25 . Them, to the reaction mixture was added MeOH (20 mL) at 025 dropwise. The reaction mixture was stirred at room temperature (25 ) for 0.5 hr and concentrated with a rotary evaporator to obtain crude 143-2 (450 mg) .

Reference： [1]Current Patent Assignee: ABBISKO THERAPEUTICS - WO2021/254005, 2021, A1 Location in patent: Page/Page column 33
[2]Current Patent Assignee: SHENZHEN CHIPSCREEN BIOSCIENCES CO LTD - WO2022/89511, 2022, A1 Location in patent: Page/Page column 29-30
[3]Al Hussainy, Rana; Verbeek, Joost; Van Der Born, Dion; Booij, Jan; Herscheid [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5728 - 5735]
[4]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1 Location in patent: Paragraph 1269
[5]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US9273058, 2016, B2 Location in patent: Page/Page column 657; 658
[6]Current Patent Assignee: ECCOGENE SHANGHAI - WO2021/83209, 2021, A1 Location in patent: Paragraph 00791

10
[ 498-66-8 ]
[ 1350821-95-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: ruthenium trichloride; sodium periodate / water; ethyl acetate; acetonitrile / 2 h / 20 °C / Cooling with ice 2.1: sulfuric acid / Reflux 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 1.25 h / -75 - -10 °C / Inert atmosphere 3.2: 0.5 h / -75 - -70 °C / Inert atmosphere 4.1: sodium hydroxide / tetrahydrofuran; methanol / 20 °C 5.1: borane-THF / tetrahydrofuran / -40 - 0 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

11
cycloheptane-1,3-dicarboxylic acid [ No CAS ]
[ 1350821-95-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sulfuric acid / Reflux 2.1: diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 1.25 h / -75 - -10 °C / Inert atmosphere 2.2: 0.5 h / -75 - -70 °C / Inert atmosphere 3.1: sodium hydroxide / tetrahydrofuran; methanol / 20 °C 4.1: borane-THF / tetrahydrofuran / -40 - 0 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

12
[ 343949-04-2 ]
[ 1350821-95-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 1.25 h / -75 - -10 °C / Inert atmosphere 1.2: 0.5 h / -75 - -70 °C / Inert atmosphere 2.1: sodium hydroxide / tetrahydrofuran; methanol / 20 °C 3.1: borane-THF / tetrahydrofuran / -40 - 0 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

13
[ 1350821-95-2 ]
methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With Dess-Martin periodane In dichloromethane at 20℃; for 18h;	Intermediate A139A: Methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate Intermediate A139A: Methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate To a solution of Intermediate A138A (0.118 g, 0.640 mmol) in DCM (5 mL) was added Dess-Martin periodinane (0.326 g, 0.769 mmol). The reaction mixture was allowed to stir at RT for 18 h. The reaction was diluted with equal parts DCM and a saturated aq. solution of NaHCO3. The organic phase was separated and the aqueous phase was extracted twice more with DCM. The combined organic layers were dried over MgSO4, and concentrated to provide a white solid. The crude reaction mixture was purified by silica gel chromatography (24 g REDISEP column, eluting with a gradient from 0-15% EtOAc in hexanes).
72%	With Dess-Martin periodane In dichloromethane at 20℃;	1.D1.3 Step 3: Synthesis of methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate In a single-neck flask containing methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate (4.75 g, 25.7 mmol), dichloromethane (180 mL) was added to dissolve it. Dess-Martin reagent (13.1 g, 30.9 mmol) was added. The reaction solution was stirred at room temperature, and the reaction was detected by TLC until the raw material disappeared. Celite was filtered, the filtrate was concentrated and separated by column chromatography (petroleum ether/ethyl acetate=5:1) to obtain methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate (3.38 g, yield 72%).
2.6 g	With pyridinium chlorochromate In dichloromethane at 0 - 20℃; for 3h;	228.F F) Methyl 4-formylbicyclo[2.2.1 ]heptane- 1 -carboxylate [ 1270] Pyridinium chlorochromate (10.1 g) was added to a solution of methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-l-carboxylate (4.30 g) in dichloromethane (80 mL) at 0°C, and the resultant was stirred for 3 hours at room temperature. The reaction mixture was filtered using celite, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by a silica gel column chromatography (hexane ethyl acetate), thereby obtaining the title compound (2.60 g). 1H NMR (400 MHz, DMSO-d6)6 1.44-1.49 (1H, m), 1.55-1.70 (3H, m), 1.81 (2H, s), 1.91-2.01 (4H, m), 3.60 (3H, s), 9.75 (1H, s).

	With Dess-Martin periodane In dichloromethane at 20℃; for 2h;	1.6 Step 6: methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate A mixture of methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate (PharmaBlock, catNo.PBZ3820: 400 mg, 2.17 mmol) and Dess-Martin periodinane (1381 mg, 3.26 mmol) in dichloromethane (12.0 mL) was stirred at room temperature for 2 h. The reaction mixture was quenched with 20% aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was used directly in the next step without further purification.
	With Dess-Martin periodane In dichloromethane at 20℃; for 2h;	20.6 Step 6; methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate A mixture of methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate (PharmaBlock, cat PBZ3820: 400 mg, 2.17 mmol) and Dess-Martin periodinane (1381 mg, 3.26 mmol) in dichloromethane (12.0 mL) was stirred at room temperature for 2 h. The reaction mixture was quenched with 20% aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was used directly in the next step without further purification.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US9273058, 2016, B2 Location in patent: Page/Page column 659; 660
[2]Current Patent Assignee: ABBISKO THERAPEUTICS - WO2021/254005, 2021, A1 Location in patent: Page/Page column 33
[3]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1 Location in patent: Paragraph 1270
[4]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1 Location in patent: Paragraph 0341; 0342
[5]Current Patent Assignee: INCYTE CORP - US2021/139511, 2021, A1 Location in patent: Paragraph 0404; 0414; 0415

14
[ 1350821-95-2 ]
methyl 4-((E)-(hydroxyimino)methyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridinium chlorochromate / dichloromethane / 3 h / 0 - 20 °C 2: sodium hydrogencarbonate; hydroxylamine hydrochloride / methanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

15
[ 1350821-95-2 ]
methyl 4-((Z)-chloro(hydroxyimino)methyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyridinium chlorochromate / dichloromethane / 3 h / 0 - 20 °C 2: sodium hydrogencarbonate; hydroxylamine hydrochloride / methanol / 2 h / 20 °C 3: N-chloro-succinimide / N,N-dimethyl-formamide / 2 h / 20 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

16
[ 1350821-95-2 ]
tert-butyl 7-(4-(methoxycarbonyl)bicyclo[2.2.1]hept-1-yl)-5-oxa-2,6-diazaspiro[3.4]oct-6-ene-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: pyridinium chlorochromate / dichloromethane / 3 h / 0 - 20 °C 2: sodium hydrogencarbonate; hydroxylamine hydrochloride / methanol / 2 h / 20 °C 3: N-chloro-succinimide / N,N-dimethyl-formamide / 2 h / 20 °C 4: triethylamine / dichloromethane / 24 h / 20 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

17
[ 1350821-95-2 ]
methyl 4-(2-((2,6-diethoxy-4'-fluorobiphenyl-4-yl)methyl)-5-oxa-2,6-diazaspiro[3.4]oct-6-en-7-yl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: pyridinium chlorochromate / dichloromethane / 3 h / 0 - 20 °C 2.1: sodium hydrogencarbonate; hydroxylamine hydrochloride / methanol / 2 h / 20 °C 3.1: N-chloro-succinimide / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: triethylamine / dichloromethane / 24 h / 20 °C 5.1: hydrogenchloride / 1,4-dioxane / 5 h / 20 °C 5.2: 0.17 h / 20 °C 5.3: 5 h / 20 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

18
[ 1350821-95-2 ]
4-(2-((2,6-diethoxy-4'-fluorobiphenyl-4-yl)methyl)-5-oxa-2,6-diazaspiro[3.4]oct-6-en-7-yl)bicyclo[2.2.1]heptane-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: pyridinium chlorochromate / dichloromethane / 3 h / 0 - 20 °C 2.1: sodium hydrogencarbonate; hydroxylamine hydrochloride / methanol / 2 h / 20 °C 3.1: N-chloro-succinimide / N,N-dimethyl-formamide / 2 h / 20 °C 4.1: triethylamine / dichloromethane / 24 h / 20 °C 5.1: hydrogenchloride / 1,4-dioxane / 5 h / 20 °C 5.2: 0.17 h / 20 °C 5.3: 5 h / 20 °C 6.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 6 h / 20 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2014/142363, 2014, A1

19
[ 1350821-95-2 ]
methyl 4-(difluoromethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Dess-Martin periodane / dichloromethane / 18 h / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 18 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US9273058, 2016, B2

20
[ 1350821-95-2 ]
methyl 4-(2-(2-((2,2'-dimethyl-3'-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

21
[ 1350821-95-2 ]
methyl 4-(2-(2-((2,2'-dichloro-3'-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / 2 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

22
[ 1350821-95-2 ]
methyl 4-(2-(2-((2-chloro-3'-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2'-methyl-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

23
[ 1350821-95-2 ]
methyl 4-(2-(2-((3'-(5-(5-(tert-butoxy)-5-oxopentyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2,2'-dichloro-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

24
[ 1350821-95-2 ]
4-(2-(2-((2,2'-dichloro-3'-(5-(5-(dimethylamino)-5-oxopentyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; hydrogenchloride / tetrahydrofuran; 1,4-dioxane / 1 h / 40 °C 5.2: 2 h / 20 °C 5.3: 3 h / 30 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

25
[ 1350821-95-2 ]
methyl 4-(2-oxoethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium-t-butoxide / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C
	Multi-step reaction with 2 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium-t-butoxide / tetrahydrofuran / 1 h / 20 °C 2.2: 5 h / 20 °C 2.3: 1 h / 20 °C
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 20 °C 2.1: potassium-t-butoxide / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 2.2: 3 h / 20 °C / Inert atmosphere 3.1: hydrogenchloride; water monomer / tetrahydrofuran / 2 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1
[2]Current Patent Assignee: INCYTE CORP - US2021/139511, 2021, A1
[3]Current Patent Assignee: ABBISKO THERAPEUTICS - WO2021/254005, 2021, A1

26
[ 1350821-95-2 ]
methyl 4-(2-(2-((2,2'-dichloro-3'-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 °C 2.2: 5 h / 20 °C 2.3: 1 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 3 h / 20 °C 3.2: 1 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1
[2]Current Patent Assignee: INCYTE CORP - US2021/139511, 2021, A1

27
[ 1350821-95-2 ]
4,4'-(((((2,2'-dichloro-[1,1'-biphenyl]-3,3'-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 °C 2.2: 5 h / 20 °C 2.3: 1 h / 20 °C 3.1: toluene-4-sulfonic acid / 2 h / 50 °C 4.1: potassium hydroxide; water / tetrahydrofuran / 3.5 h / 40 °C 5.1: hydrogenchloride / tetrahydrofuran; water / 1.5 h / 20 °C 6.1: dichloromethane; isopropyl alcohol / 1.5 h 6.2: 2.5 h / 20 - 35 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2021/139511, 2021, A1

28
[ 1350821-95-2 ]
methyl 4-(2-(2-((2-chloro-2'-methyl-3'-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

29
[ 1350821-95-2 ]
methyl 4-(2-(2-((2'-chloro-2-methyl-3'-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

30
[ 1350821-95-2 ]
methyl 4-(2-(2-((2-chloro-2'-cyano-3'-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

31
[ 1350821-95-2 ]
4-(2-(2-((2,2'-dimethyl-3'-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol / 3 h / 30 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

32
[ 1350821-95-2 ]
4,4'-(((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid) trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 3 h / 30 °C 3.3: pH 2
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 4.2: 3 h / 30 °C 4.3: pH 2

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1
[2]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

33
[ 1350821-95-2 ]
(R)-4-(2-(2-((3'-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / 2 h / 20 °C 4.2: 2 h / 40 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

34
[ 1350821-95-2 ]
4-(2-(2-((2,2’-dichloro-3’-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1’-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / 2 h / 20 °C 5.1: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol 5.2: pH 2

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

35
[ 1350821-95-2 ]
4-(2-(2-((3'-(5-(2-(trans-4-carboxycyclohexyl)ethyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2,2'-dichloro-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 4.2: 3 h / 30 °C 4.3: pH 2

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

36
[ 1350821-95-2 ]
4-(2-(2-((3'-(5-(4-carboxybutyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2,2'-dichloro-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 5.1: hydrogenchloride / tetrahydrofuran; 1,4-dioxane / 1 h / 40 °C 5.2: 3 h / 30 °C 5.3: pH 2

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

37
[ 1350821-95-2 ]
4-(2-(2-((3'-(5-(cis-4-carboxy-4-methylcyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2,2'-dichloro-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 40 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

38
[ 1350821-95-2 ]
4-(2-(2-((2-chloro-3’-(5-(4-hydroxycyclohexyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-2’-methyl-[1,1’-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 5.1: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol / 2 h / 30 °C 5.2: pH 2

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

39
[ 1350821-95-2 ]
4-(2-(2-((2,2'-dichloro-3'-(1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol / 3 h / 30 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

40
[ 1350821-95-2 ]
4-(2-(2-((2,2'-dichloro-3'-(1-methyl-5-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 4.2: 3 h / 30 °C 4.3: pH 2

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

41
[ 1350821-95-2 ]
(R)-4-(2-(2-((2,2'-dichloro-3'-(5-(2-hydroxypropyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-2-carboxamido)-[1,1'-biphenyl]-3-yl)carbamoyl)-1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)ethyl)bicyclo[2.2.1]heptane-1-carboxylic acid trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 4.2: 2 h / 40 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1

42
[ 1350821-95-2 ]
4,4'-(((((2,2'-dichloro-[1,1'-biphenyl]-3,3'-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid) trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C
	Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 250 °C 2.2: 5 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C
	Multi-step reaction with 3 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 °C 2.2: 5 h / 20 °C 2.3: 1 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 3.2: 3 h / 30 °C 3.3: pH 8

Multi-step reaction with 4 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 °C 2.2: 5 h / 20 °C 2.3: 1 h / 20 °C 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 3 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 °C 4.2: 3 h / 30 °C 4.3: pH 8

Reference： [1]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1
[2]Current Patent Assignee: INCYTE CORP - US2019/345170, 2019, A1
[3]Current Patent Assignee: INCYTE CORP - US2021/139511, 2021, A1
[4]Current Patent Assignee: INCYTE CORP - US2021/139511, 2021, A1

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CAS No. :	1350821-95-2	MDL No. :	MFCD26727798
Formula :	C₁₀H₁₆O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	N/A
M.W :	184.23 g/mol	Pubchem ID :	-
Synonyms :

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:
Hazard Statements:	H302-H315-H319-H335	Packing Group:
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
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P103	Read label before use
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P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
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P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1350821-95-2 ]

Quality Control of [ 1350821-95-2 ]

Related Doc. of [ 1350821-95-2 ]

Product Details of [ 1350821-95-2 ]

Safety of [ 1350821-95-2 ]

Application In Synthesis of [ 1350821-95-2 ]

[ 1350821-95-2 ] Synthesis Path-Downstream 1~42

Related Functional Groups of
[ 1350821-95-2 ]

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 1350821-95-2 ]

Quality Control of [ 1350821-95-2 ]

Related Doc. of [ 1350821-95-2 ]

Product Details of [ 1350821-95-2 ]

Safety of [ 1350821-95-2 ]

Application In Synthesis of [ 1350821-95-2 ]

[ 1350821-95-2 ] Synthesis Path-Downstream 1~42

Related Functional Groups of [ 1350821-95-2 ]

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1350821-95-2 ]