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Quality Control of [ 1408074-81-6 ]

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Product Details of [ 1408074-81-6 ]

CAS No. :	1408074-81-6	MDL No. :	MFCD23106118
Formula :	C₁₃H₂₁NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FZDJDEXABKVIDA-UHFFFAOYSA-N
M.W :	255.31	Pubchem ID :	72208124
Synonyms :

Safety of [ 1408074-81-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P264-P270-P301+P312-P330	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1408074-81-6 ]

* 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 [ 1408074-81-6 ]

[ 1408074-81-6 ] Synthesis Path-Downstream 1~30

1
[ 1408074-81-6 ]
[ 2151817-08-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium amide / tetrahydrofuran / 3 h / -33 °C 2.2: 12 h / 20 °C 2.3: 0 °C

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2017/197036, 2017, A1

2
[ 3395-91-3 ]
[ 1408074-81-6 ]
[ 2151817-07-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-(tert-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: Methyl 3-bromopropionate In tetrahydrofuran at -78 - 20℃;	7 2-(tert-Butyl) 6-methyl 6-(3-methoxy-3-oxopropyl)-2-azaspiro[3.3]heptane-2,6- dicarboxylate 2-(t-Butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (1 equiv.) is dissolved in dry THF and cooled to-78 °C. A solution of LiHMDS (1.0 M in THF) (1.1 equiv.) is then added dropwise and the solution is stirred for 1 hour. Methyl 3-bromopropanoate (1 equiv.) was then added dropwise. The is allowed to stir for 30 minutes and is then warmed gradually to room temperature. When the reaction is judged to be complete based on TLC or LCMS analysis, it is quenched with saturated aqueous ammonium chloride solution and diluted with ethyl acetate. The organic layer is separated and the aqueous layer is extracted with ethyl acetate (3x). The combined organic layers are washed with brine and dried over sodium sulfate before concentrating under reduced pressure. The crude product is then purified on silica providing 2-(tert-butyl) 6-methyl 6- (3-methoxy-3-oxopropyl)-2-azaspiro[3.3]heptane-2,6-dicarboxylate.

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2017/197036, 2017, A1 Location in patent: Page/Page column 300

3
[ 1408074-81-6 ]
[ 2254567-66-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 1.2: 80 °C / Inert atmosphere 2.1: hydrazine hydrate / methanol / 20 °C 3.1: 1,4-dioxane / 36 h / 90 °C

Reference： [1]Current Patent Assignee: BLACKTHORN THERAPEUTICS INC - WO2018/226769, 2018, A1

4
[ 1408074-81-6 ]
[ 2254584-66-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 1.2: 80 °C / Inert atmosphere 2.1: hydrazine hydrate / methanol / 20 °C

Reference： [1]Current Patent Assignee: BLACKTHORN THERAPEUTICS INC - WO2018/226769, 2018, A1

5
[ 1408074-81-6 ]
[ 2254567-24-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 1.2: 80 °C / Inert atmosphere 2.1: hydrazine hydrate / methanol / 20 °C 3.1: acetic acid / isopropyl alcohol / 1.5 h / 80 °C

Reference： [1]Current Patent Assignee: BLACKTHORN THERAPEUTICS INC - WO2018/226769, 2018, A1

6
[ 1408074-81-6 ]
[ 2254586-23-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 1.2: 80 °C / Inert atmosphere 2.1: hydrazine hydrate / methanol / 20 °C 3.1: 1,4-dioxane / 36 h / 90 °C 4.1: hydrogenchloride / methanol; 1,4-dioxane / 6 h / 20 °C

Reference： [1]Current Patent Assignee: BLACKTHORN THERAPEUTICS INC - WO2018/226769, 2018, A1

7
[ 1408074-81-6 ]
[ 2254567-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 1.2: 80 °C / Inert atmosphere 2.1: hydrazine hydrate / methanol / 20 °C 3.1: 1,4-dioxane / 36 h / 90 °C 4.1: hydrogenchloride / methanol; 1,4-dioxane / 6 h / 20 °C 5.1: methanol / 6 h / 70 °C 5.2: 0 - 20 °C

Reference： [1]Current Patent Assignee: BLACKTHORN THERAPEUTICS INC - WO2018/226769, 2018, A1

8
[ 109-04-6 ]
[ 1408074-81-6 ]
[ 2254584-64-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 2-(tert-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate With trifluoroacetic acid In dichloromethane at 20℃; for 1h; Stage #2: 2-bromo-pyridine With palladium diacetate; caesium carbonate; ruphos In 1,4-dioxane at 80℃; Inert atmosphere;	6.4 Step 4: Synthesis of methyl 2-(pyridin-2-yl)-2-azaspiro[3.3]heptane-6-carboxylate To a solution of 2-(tert-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6- dicarboxylate (1.10 g, 4.31 mmol, 1.0 eq.) in DCM (15mL) was added TFA (5 mL) and the mixture was stirred at RT for 1 hour. Toluene was added and the mixture was concentrated in vacuo to give a yellow oil. A mixture of the yellow oil (0.58 g, 2.15 mmol, 1.0 eq.), 2-bromopyridine (247 µL, 2.59 mmol, 1.2 eq.), RuPhos (0.201 g, 0.43 mmol, 0.20 eq.), palladium acetate (0.048 g, 0.22 mmol, 0.1 eq.), cesium carbonate (2.106 g, 6.46 mmol, 3.0 eq.) in dioxane (10 mL) was de-gassed using nitrogen for 10 minutes and heated to 80°C overnight. The mixture was diluted with EtOAc, filtered through a layer of celite and the filtrate was concentrated in vacuo . The residue was purified by flash column chromatography (Biotage KP-NH) eluting with 0-50% EtOAc in Isohexane to give the title compound as a pale yellow oil. (0.40 g, 80% yield). H NMR (400 MHz, CDCl3) δ 8.13 (dd, J=1.0, 5.1 Hz, 1H), 7.45 - 7.40 (m, 1H), 6.58 (dd, J=5.2, 6.2 Hz, 1H), 6.26 (d, J=8.6 Hz, 1H), 4.04 (s, 2H), 3.97 (s, 2H), 3.70 (s, 3H), 3.09 - 3.02 (m, 1H), 2.53 - 2.47 (m, 4H).

Reference： [1]Current Patent Assignee: BLACKTHORN THERAPEUTICS INC - WO2018/226769, 2018, A1 Location in patent: Page/Page column 156-157

9
[ 1408074-81-6 ]
[ 2419912-88-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: lithium diisopropyl amide / tetrahydrofuran / 13 h / -78 - 20 °C 2: sodium hydroxide; methanol / 15 h / 50 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2020/96916, 2020, A2

10
[ 513-38-2 ]
[ 1408074-81-6 ]
[ 2419912-87-9 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; for 13h;	23.2 Step 2: preparation of 2-tert-butyl 6-methyl 6-isobutyl-2-azaspiror3.31hentane-2.6-dicarboxylate (B5 B): LDA (0.58 mL, 1.160 mmol) was added to a stirred mixture of l-iodo-2-methylpropane (360 mg, 1.958 mmol) and 2-tert-butyl 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate(B5_A, 100 mg, 0.392 mmol) in THF (3 mL) at -78°C, and the mixture was stirred at -78°C for 3 h, then at rt for 10 h. The mixture was quenched with NLLCl (10 mL), extracted with EtOAc (10 mL*3), the combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (ISCO;4 g SepaFlashSilica Flash Column, Eluent of 0-10% EtOAc/Petro. Ether gradient 40 mL/min) to give 2-tert-butyl 6-methyl 6-isobutyl-2-azaspiro[3.3]heptane-2,6-dicarboxylate (B5_B).1H NMR (400 MHz, CDCl3) d 3.87 (d, J= 3.1 Hz, 4H), 3.69 (s, 3H), 2.68-2.58 (m,1H), 2.18-2.09 (m, 1H), 1.67-1.61 (m, 3H), 1.59-1.48 (m, 1H), 1.42 (s, 9H), 0.83 (d, J= 6.7 Hz, 6H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2020/96916, 2020, A2 Location in patent: Page/Page column 55; 56

11
[ 1408074-81-6 ]
[ 2055497-44-2 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid In dichloromethane at 20℃; for 2h;	26.1 Step 1: Preparation of methyl 2-azaspiro[3.3]heptane-6-carboxylate trifluoroacetic acid (i26-2) A mixture of 2-tert-butyl 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (127.60 mg, 0.500 mmol, 1.00 equiv) and TFA (1 mL) in DCM (3.00 mL) was stirred for 2 hours at room temperature. Then, the solvent was evaporated, and the resulting residue was used in the next step directly without further purification. LCMS (ESI) m/z: [M+H]+ = 156.

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160198, 2020, A1 Location in patent: Page/Page column 269

12
[ 1408074-81-6 ]
[ 2467422-97-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 2: triethylamine; sodium cyanoborohydride; methanol / 20 °C

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160198, 2020, A1

13
[ 1408074-81-6 ]
[ 2467422-99-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 2: triethylamine; sodium cyanoborohydride; methanol / 20 °C 3: lithium hydroxide / water; tetrahydrofuran / 1 h / 20 °C

Reference： [1]Current Patent Assignee: FOGHORN THERAPEUTICS INC - WO2020/160198, 2020, A1

14
[ 1408074-81-6 ]
[ 1363381-93-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium tetrahydridoborate In tetrahydrofuran; methanol at 20℃;	125 125: 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((2-(2-(2-,2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)-2-azaspiro[3.3]heptan-6-yl)methyl)amino)phenyl)cyclo propane-1-carbonitrile (125) [0389] Compound 2-(t-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (765 mg, 3.00 mmol) was added to 5 mL of THF, and then 1 mL of MeOH was added to aid the solubility of the compound, followed by addition of NaBH4 in an ice bath. After addition, the ice bath was removed, and the mixture was stirred overnight at room temperature. The reaction solution was diluted with DCM. The organic phase was washed with saturated NH4Cl solution, saturated NaHCO3 solution, and saturated NaCl solution, and then dried over anhydrous sodium sulfate, and rotatory evaporated to dry, to provide t-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (579 mg, 2.55 mmol), with a yield of 85%. LC/MS (ESI+) calcd for: C12H21NO3 (M + H+) m/z, 228.2; found, 228.2.
85%	With sodium tetrahydridoborate In tetrahydrofuran; methanol at 20℃;	125 125: 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((2-(2-(2-,2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)-2-azaspiro[3.3]heptan-6-yl)methyl)amino)phenyl)cyclo propane-1-carbonitrile (125) [0389] Compound 2-(t-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (765 mg, 3.00 mmol) was added to 5 mL of THF, and then 1 mL of MeOH was added to aid the solubility of the compound, followed by addition of NaBH4 in an ice bath. After addition, the ice bath was removed, and the mixture was stirred overnight at room temperature. The reaction solution was diluted with DCM. The organic phase was washed with saturated NH4Cl solution, saturated NaHCO3 solution, and saturated NaCl solution, and then dried over anhydrous sodium sulfate, and rotatory evaporated to dry, to provide t-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (579 mg, 2.55 mmol), with a yield of 85%. LC/MS (ESI+) calcd for: C12H21NO3 (M + H+) m/z, 228.2; found, 228.2.
85%	With sodium tetrahydridoborate In tetrahydrofuran; methanol at 20℃;	125 125: 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((2-(2-(2-,2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)-2-azaspiro[3.3]heptan-6-yl)methyl)amino)phenyl)cyclo propane-1-carbonitrile (125) [0389] Compound 2-(t-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (765 mg, 3.00 mmol) was added to 5 mL of THF, and then 1 mL of MeOH was added to aid the solubility of the compound, followed by addition of NaBH4 in an ice bath. After addition, the ice bath was removed, and the mixture was stirred overnight at room temperature. The reaction solution was diluted with DCM. The organic phase was washed with saturated NH4Cl solution, saturated NaHCO3 solution, and saturated NaCl solution, and then dried over anhydrous sodium sulfate, and rotatory evaporated to dry, to provide t-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate (579 mg, 2.55 mmol), with a yield of 85%. LC/MS (ESI+) calcd for: C12H21NO3 (M + H+) m/z, 228.2; found, 228.2.

With sodium tetrahydridoborate

125: 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((2-(2-(2-,2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)-2-azaspiro[3.3]heptan-6-yl)methyl)amino)phenyl)cyclo propane-1-carbonitrile (125) Compound 2-(t-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (765 mg, 3.00 mmol) was added to 5 mL of THF, and then 1 mL of MeOH was added to aid the solubility of the compound, followed by addition of NaBH4 in an ice bath. After addition, the ice bath was removed, and the mixture was stirred overnight at room temperature. The reaction solution was diluted with DCM. The organic phase was washed with saturated NH4Cl solution, saturated NaHCO3 solution, and saturated NaCl solution, and then dried over anhydrous sodium sulfate, and rotatory evaporated to dry, to provide t-butyl 6-(hydroxymethyl)-2-azaspiro[3.3] heptane-2-carboxylate (579 mg, 2.55 mmol), with a yield of 85%. LC/MS (ESI+) calcd for: C12H21NO3 (M + H+) m/z, 228.2; found, 228.2.

Reference： [1]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1 Location in patent: Paragraph 0388-0389
[2]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1 Location in patent: Paragraph 0388-0389
[3]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1 Location in patent: Paragraph 0388-0389
[4]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1

15
[ 1408074-81-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium tetrahydridoborate 2: sodium hydrogen sulphate
	Multi-step reaction with 2 steps 1: sodium tetrahydridoborate / tetrahydrofuran; methanol / 20 °C 2: 1H-imidazole; triphenylphosphine; iodine / tetrahydrofuran / 20 °C

Reference： [1]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1
[2]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1

16
[ 67-56-1 ]
[ 1211526-53-2 ]
[ 1408074-81-6 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride at 0℃; for 2h;	1.1 (1) Preparation of 2-(tert-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate 2-(tert-butoxycarbonyl)-2-azaspiro[3.3]heptane-6-carboxylic acid (200 mg, 0.83 mmol) was dissolved in methanol (10 mL), and thionyl chloride (2 mL) was added , stirred at 0°C for 2 hours, and spin-dried to obtain the product (220 mg, crude product).

Reference： [1]Current Patent Assignee: SHANDONG XIANBAMBUSA MEDICINE SCIENCE AND TECH - CN114181198, 2022, A Location in patent: Paragraph 0172-0175

17
[ 1408074-81-6 ]
[ 2764822-65-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 5 h / -78 - 20 °C 3: N-ethyl-N,N-diisopropylamine / acetonitrile / 20 h / 60 °C

Reference： [1]Current Patent Assignee: SHANDONG XIANBAMBUSA MEDICINE SCIENCE AND TECH - CN114181198, 2022, A

18
[ 1408074-81-6 ]
[ 2764822-28-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 5 h / -78 - 20 °C 3: N-ethyl-N,N-diisopropylamine / acetonitrile / 20 h / 60 °C 4: sodium hydroxide; water monomer / tetrahydrofuran / 1 h / 20 °C

Reference： [1]Current Patent Assignee: SHANDONG XIANBAMBUSA MEDICINE SCIENCE AND TECH - CN114181198, 2022, A

19
[ 1408074-81-6 ]
[ 1607014-48-1 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid In dichloromethane at 20℃; for 2h;	1.2 (2) Preparation of methyl 2-azaspiro[3.3]heptane-6-carboxylate 2-(tert-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate (220 mg, crude) was dissolved in DCM (5 mL) followed by TFA (5 mL) , reacted at 20° C. for 2 hours, added NaHCO 3 to adjust the pH to 8, separated the layers, and the organic phase was spin-dried to obtain the product (140 mg, crude product).
	With t-butyldimethylsiyl triflate In dichloromethane at 0 - 20℃; for 2h;	S39 Synthesis of methyl 2-azaspiro[3.3]heptane-6-carboxylate. To a solution of 2-(tert-butyl) 6-methyl 2-azaspiro[3.3]heptane-2,6-dicarboxylate ( 1.0 g, 3.922 mmol, 1.00 equiv.) in DCM (10 mL) was added TBSOTf (2.1 g, 7.843 mmol, 2.00 equiv.) dropwise at 0 °C. The resulting solution was stirred at room temperature for 2 h. LCMS showed the reaction was complete. The resulting solution was concentrated under reduce pressure. The crude methyl 2-azaspiro[3.3]heptane-6-carboxylate (700 mg) was used directly for the next step without further purification. LCMS (ESI, m/z): 156 [M-H]+.

Reference： [1]Current Patent Assignee: SHANDONG XIANBAMBUSA MEDICINE SCIENCE AND TECH - CN114181198, 2022, A Location in patent: Paragraph 0172; 0176-0178
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2022/140555, 2022, A1 Location in patent: Paragraph 00414

20
[ 1408074-81-6 ]
[ 2764822-64-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 5 h / -78 - 20 °C

Reference： [1]Current Patent Assignee: SHANDONG XIANBAMBUSA MEDICINE SCIENCE AND TECH - CN114181198, 2022, A

21
[ 1408074-81-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium tetrahydridoborate / tetrahydrofuran; methanol / 20 °C 2: 1H-imidazole; triphenylphosphine; iodine / tetrahydrofuran / 20 °C 3: sodium hydride / N,N-dimethyl-formamide / 60 °C

Reference： [1]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1

22
[ 1408074-81-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium tetrahydridoborate / tetrahydrofuran; methanol / 20 °C 2: 1H-imidazole; triphenylphosphine; iodine / tetrahydrofuran / 20 °C 3: sodium hydride / N,N-dimethyl-formamide / 60 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1

23
[ 1408074-81-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium tetrahydridoborate / tetrahydrofuran; methanol / 20 °C 2: 1H-imidazole; triphenylphosphine; iodine / tetrahydrofuran / 20 °C 3: sodium hydride / N,N-dimethyl-formamide / 60 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 5: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 3 h / 130 °C

Reference： [1]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1

24
[ 1408074-81-6 ]
[ 2794914-50-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: t-butyldimethylsiyl triflate / dichloromethane / 2 h / 0 - 20 °C 2: anhydrous zinc chloride; sodium cyanotrihydridoborate / methanol / 80 °C / Inert atmosphere 3: potassium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide / N,N-dimethyl-formamide / 15 h / 80 °C / Inert atmosphere 4: lithium hydroxide monohydrate; lithium hydroxide monohydrate / tetrahydrofuran / 15 h / 20 °C