Name: 23111-00-4|3-Carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium chloride|98%
Brand: Ambeed
SKU: A990719
Price: 6.0 USD
Availability: InStock
Rating: 90 (22 reviews)

1
[ 109527-15-3 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
89.3%	With ammonia In methanol at -3℃; for 24h;	1-5 Dissolve 1 g of triacetyl nicotinamide ribose chloride salt in 10 mL of methanol to obtain a triacetyl nicotinamide ribose chloride salt solution;Add 6 mL of 10% ammonia methanol solution to the triacetyl nicotinamide ribose chloride salt solution at -3°C, and carry out the deacetylation reaction at -3°C for 24 hours.Then, the solvent was removed by rotary evaporation at 40°C;The solid obtained by rotary evaporation is washed with ethyl acetate, the washed solution is subjected to vacuum distillation, and the solid obtained by vacuum distillation is dissolved in ethanol for recrystallization.The white solid β-nicotinamide riboside chloride was obtained by filtration. The purity of β-nicotinamide riboside chloride was 99.7% and the yield was 89.3%.
82%	With ammonia In methanol at -15 - -10℃;	3; 4; 6.1; 6.2 Procedure: Methanolic NH3 is added to nicotinamide riboside triacetate and kept overnight at -15 to -10° C.. Methanol was added to the crude and co-distilled. Methanol was added (2 vol.) and pH was adjusted to 4-5 with HCl in methanol. The methyl tert butyl ether (MTBE) (1 vol.) was added and stirred for 30 minutes at room temperature. Light brown product was formed with 82% yield.
78%	With ethanol; ammonia at 10 - 20℃; for 3h;	Add 201 grams of Compound B (0.5 mol) dissolved in 1 liter of 90% ethanol to a three-necked bottle, control the temperature at about 10-20°C and pass 25.5 grams of ammonia gas (1.5 mol), and keep warm for 3 hours, after the reaction The reaction liquid was cooled to -10°C, a large amount of solids were precipitated, filtered, and the filter cake was washed with a small amount of absolute ethanol and dried to obtain 94 g of nicotinamide ribose chloride, with a yield of 78% and a purity of 99.4%.

78%	With methanol; ammonia at -5 - 0℃; for 12h; Large scale;	1; 2 Step 2: Deacetylation reaction: Add 20L of 4N ammonia methanol solution to the pale yellow oil, control the temperature at -5-0°C, and react for 12 hours. The TLC dot panel monitors that the raw material has reacted completely. HPLC monitoring shows that the product accounts for more than 90%, and the reaction is stopped. Control the temperature below 30 degrees to distill off excess ammonia and methanol to obtain a yellow oil. Step 3: Recrystallization: The yellow oil was dissolved in 24L of ethyl acetate, heated to 40°C to dissolve and clarified, then slowly cooled to precipitate a white solid, and the temperature was controlled at 5°C to continue crystallization for 3 hours. The solvent was removed by filtration, and the filter cake was washed with 5L of ethyl acetate. , 35 blast drying to remove the solvent to obtain the target product, obtain 1.88Kg β-nicotinamide riboside chloride, the mass yield is 78%, and the purity is 99.8%.
64%	With hydrogenchloride In methanol; ethanol at 20℃; for 4h;	8 Example 8: Preparation of nicotinamide- -D-ribofuranoside chloride of formula O- Ib by deprotection of nicotinamide-2, 3, 5-tri-0-acetyl- -D-ribofuranoside chloride of formula O-Vb [00175] General procedure: Nicotinamide-tri-0-acetyl-3-D-ribofuranoside chloride was dissolved in methanol (4.9 ml_/g). Afterwards 2 equivalents of a solution of hydrochloric acid in ethanol (7.6 N) was added dropwise and the reaction mixture was stirred for 4 h at r.t. The crude product was filtered, washed with isopropyl alcohol and methanol and dried over 48 hours under reduced pressure to yield the pure nicotinamide-3-D- ribofuranoside chloride as a white solid (49-64 %). a) Nicotinamide-tri-0-acetyl-3-D-ribofuranoside chloride = 1.95 kg (4.679 mol) in 9.5 L MeOH7.6 N HCI (9.357 mol, 2.0 eq., 1.231 L)4 h at r.t.1 2 L IPA, 12 L MeOHNicotinamide-3-D-ribofuranoside chloride = 672 g (2.312 mol, 49 %) b) Nicotinamide-tri-O-acetyl-beta-D-ribofuranoside chloride = 1.70 kg (4.079 mol) in 8.5 L MeOH7.6 N HCI (2.0 eq., 8.157 mol, 1.073 L)4 h at r.t.1 2 L IPA, 1 2 L MeOHNicotinamide-3-D-ribofuranoside chloride = 757 g (2.604 mol, 64 %)Purity (HPLC) 99.3 area-%Impurity (Nicotinamide) 0.3 %1H-NMR (400 MHz, D20) d ppm 3.85 (dd, J=13.0, 3.5 Hz, 1 H) 3.96 - 4.03 (m, 1 H) 4.29 - 4.34 (m, 1 H) 4.40 - 4.50 (m, 2 H) 6.21 (d, J=4.6 Hz, 1 H) 8.24 (t, J=6.8 Hz, 1 H) 8.94 (d, J= 8.3 Hz, 1 H) 9.23 (d, J=6.1 Hz, 1 H) 9.55 (s, 1 H).
60%	With ammonia In methanol at 0℃; for 14h; Large scale;	1 Example 1. Scale-Up Synthesis and Crystallization of Nicotinamide Riboside Chloride 900 kg of nicotinamide riboside triacetate and 2133 kg of methanol were charged to a reactor and mixed, then cooled to 0 °C. 747 kg of 7M mmmonia in methanol (i.e.,“methanolic NH3”) was slowly charged to the reactor at 0 °C. The reaction mixture was passed through a polish filter, then the reaction mixture was stirred for 14 hours. A sample from the reaction mixture was taken to assess reaction progress. Upon completion of the reaction, the reaction mixture was placed under vacuum, then warmed to 20 °C to 25 °C for 4 hours. Vacuum was applied until solids formed. Once solids were formed, the resultant slurry was filtered on a Nutsche filter dryer. Solids were washed with 1422 kg of ethanol, then 1422 kg of acetone, then 1322 kg of methyl tert butyl ether (MTBE). The resultant solids were then dried at 40 °C. Product was formed with 60% yield. The process flow diagram for this reaction is shown in FIG. 6
	With methanol; ammonia
	With hydrogenchloride In methanol for 12h; Sealed tube;	1.E Optimized Deprotection Reactions Reaction in Methanol: The deprotection was conducted on Compound 2 on a 5-gram scale, using 3 equiv. 1.25 M anhydrous HCl in MeOH under sealed conditions. As full deprotection occurred, Compound 5 began to precipitate out of solution. After twelve hours, the suspension in the sealed tube was filtered under reduced pressure and the cake was washed with small volumes of EtOH. NMR of the cake (FIG. 11(a)) and of the supernatant (FIG. 11(b)) were taken. NMR of the cake (FIG. 11(a)) showed complete deprotection with only trace amounts of impurities. The supernatant (FIG. 11(b)) is shown to contain some amount of Compound 5 as well as partially deprotected material and small amounts of reaction by-products.
	With methanol; propylamine at -5℃; for 22h;	1.3; 2.3; 3.3 S3, adding 1000 mL of methanol to the above reaction kettle, cooling to -5°C, adding 60 mL of n-propylamine and reacting for 22 hours to obtain a reaction solution containing nicotinamide riboside

Reference： [1]Current Patent Assignee: BAYECAO HEALTH INDUSTRY RES INSTITUTE XIAMEN - CN113621004, 2021, A Location in patent: Paragraph 0039; 0078; 0082-0098
[2]Current Patent Assignee: ELYSIUM HEALTH INC - US2020/140475, 2020, A1 Location in patent: Paragraph 0242; 0243; 0249-0251
[3]Current Patent Assignee: GIHI CHEMICALS - CN111153953, 2020, A Location in patent: Paragraph 0024; 0026
[4]Current Patent Assignee: EFFEPHARM SHANGHAI - CN112457353, 2021, A Location in patent: Paragraph 0017; 0024-0029
[5]Current Patent Assignee: KKR & CO LP - WO2019/219895, 2019, A1 Location in patent: Paragraph 00175
[6]Current Patent Assignee: ELYSIUM HEALTH INC - WO2019/126482, 2019, A1 Location in patent: Page/Page column 29; 30
[7]Haynes et al. [Journal of the Chemical Society, 1957, p. 3727,3731]
[8]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST; CHROMADEX CORP. - US2018/134743, 2018, A1 Location in patent: Paragraph 2716-2718; 2723-2726; 2804-2807
[9]Current Patent Assignee: SHANGHAI SHUZE BIOLOGICAL TECH RESEARCH INSTITUTE - CN111647032, 2020, A Location in patent: Paragraph 0027; 0029; 0031

2
[ 122620-02-4 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
52.6%	With sodium methylate In methanol at -5℃; for 24h;	4-7 10.2g of oily substance was dissolved in 50ml of anhydrous methanol, 4.8g (90mmol) of sodium methoxide was added, the reaction temperature was controlled at -5°C, and the reaction was carried out for 24 hours. TLC (n-BuOH/H2O/AcOH=5:3:2) detects the completion of the reaction. After the reaction was completed, a large amount of solid was precipitated out of the reaction liquid, which was filtered with suction. Discard the filtrate, wash the filter cake with 100ml ethyl acetate slurry, and filter with suction, the ethyl acetate layer was discarded, 100ml of tetrahydrofuran:methanol=10:1 solution was added to the solid, the slurry was washed, and the white solid 18.4 was obtained by suction filtration, with a total yield of about 52.6%.
	With methanol; ammonia
0.28 g	With ammonia In methanol at -32℃; for 120h;	Synthesis of b-nicotinamide riboside chloride b-nicotinamide riboside tribenzoate chloride (1 .0 g, 1.66 mmol) was dissolved in MeOH (15 ml.) and the resulting solution was cooled to -32 °C. Over this cooled solution was added dropwise a solution of NH3 7 N in methanol (280 mmol, 40 ml_). The resulting mixture was stirred at the same temperature for 120 h. Then, the MeOH and the ammonia in excess were removed using a high vacuum pump (Telstar 2G-6, 4.10-2 mbar) yielding the title compound together with benzamide as white syrup. This residue was cleaned with diethyl ether (3 x 50 ml.) and with dichloromethane (3 x 50 ml.) to remove the benzamide by-product yielding the b-nicotinamide riboside chloride pure product as a white solid (0.28 g, 0.96 mmol, 57% yield). 1H NMR (D20): d 9.64 (tt, J = 1 .5, 0.6 Hz, 1 H), 9.30 (dq, J = 6.4, 1.1 Hz, 1 H), 9.02 (dt, J = 8.2, 1.5 Hz, 1 H), 8.31 (dd, J = 8.1 , 6.3 Hz, 1 H), 6.28 (d, J = 4.5 Hz, 1 H), 4.61 - 4.47 (m, 2H), 4.39 (dd, J = 5.0, 4.3 Hz, 1 H), 4.09 (dd, J = 12.9, 2.9 Hz, 1 H), 3.93 (dd, J = 13.0, 3.6 Hz, 1 H). 13C NMR (D20): d 166.1 , 146.1 , 143.0, 141.0, 134.4, 128.9, 100.4, 88.1 , 77.9, 70.2, 60.6. 19F NMR (D20): d -78.90.

Reference： [1]Current Patent Assignee: FUJIAN KANGHONG BIOLOGICAL TECH - CN111892635, 2020, A Location in patent: Paragraph 0022; 0052; 0054; 0055; 0057; 0058; 0060-0063
[2]Haynes et al. [Journal of the Chemical Society, 1957, p. 3727,3731]
[3]Current Patent Assignee: STEMTEK THERAPEUTICS SL - WO2019/122084, 2019, A1 Location in patent: Page/Page column 16

3
[ 23111-00-4 ]
[ 1094-61-7 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate;	The reaction to produce Compound 6 by extrusion was performed on the ThermoFisher twin screw extruder 11 mm, using a feed rate of 10 g/min with a 1:4 ratio of nicotinamide riboside to 46 POCl3. The extruder came to a grinding halt as it was difficult to control the feed rate of POCl3. The machine was opened and samples were removed from mixing zone 1 and mixing zone 2 and submitted for NMR analysis. Mixing zone 1 showed the material to be slightly charred but conversion to Compound 6 was observed, along with the presence of by-products. Mixing zone 2 did not appear to show any charring. NMR showed approximately 46% conversion to Compound 6, along with the presence of by-products. The extruder was cleaned to clear the mixing zone from the hardened material that had formed in order to prevent torque on the screw, and a second run was attempted. Run 2 was performed using a feed rate of 7 g/min with a 1:3 ratio of nicotinamide riboside to POCl3. Once again, after the machine came to a halt, the machine was opened and samples were removed from mixing zone 1 and mixing zone 2 and submitted for NMR analysis. Mixing zone 1 showed approximately 30% conversion to Compound 6 with no evidence of apparent darkening of the mixture by observation. Mixing zone 2 showed approximately 15% conversion to Compound 6. A sample of the material that came out of the extruder showed approximately 6% conversion to 10 Compound 6 by NMR. 1H NMR (D2O, 400 MHz): delta ppm 9.32 (s, 1H, aromatic), 9.13 (m, 1H, aromatic), 8.89 (dt, J=8.0, 1.3 Hz, 1H, aromatic), 8.19 (dd, J=8.0, 6.5 Hz, 1H, aromatic), 6.04 (d, J=5.5 Hz, 1H, H-1 (anomeric)), 4.54 (m, 1H, H-2), 4.46 (t, J=5.1 Hz, 1H, H-3), 4.34 (dd, J=5.0, 2.5 Hz, 1H, H-4), 4.21 (ABX, JA,A?=12.0, 4.0 Hz, 1H, H-5), 4.05 (ABX, JA,B=12.0, 4.0 Hz, 1H, H-5). 13C NMR (D2O, 100 MHz): delta ppm 165.6 (C(?O)NH2), 146.0, 142.5, 139.9, 133.9, 128.5 (aromatic), 99.9 (C-1 (anomeric)), 89.4 (C-4), 77.7 (C-2), 70.9 (C-3), 64.1 (C-5). 31P NMR (D2O, 162 MHz): delta ppm 0.03. HRMS (ES, M+H+) calculated 357.0464 for C11H15N2O8PNa, found 357.0479.
10 g	With trimethyl phosphite; trichlorophosphate; at -10 - -7℃; for 24h;	A mixture of crude nicotinamide nucleoside (40 g, 0.065 mol) and trimethyl phosphate (150 ml) at -10 to -7 C was added dropwise phosphorus oxychloride (40 g, 0.26 mol). Kept at -10 to -7 C, with stirring, reacting for 24 hours. The reaction mixture was poured into ice water (150 ml), extracted with dichloromethane (300 ml), and the aqueous layer was neutralized with a 30% liquid base at -10 to -0 C to give nicotinamide. An aqueous solution of a single nucleotide was desalted with D301 resin and lyophilized to give a solid nicotinamide mononucleotide (10 g, 32%).

Reference： [1]Journal of the Chemical Society,1957,p. 3727,3731
[2]Patent: US2018/134743,2018,A1 .Location in patent: Paragraph 2748-2751
[3]Patent: CN108774278,2018,A .Location in patent: Paragraph 0039-0040; 0043; 0046

4
[ 105499-44-3 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetonitrile 2: NH₃; methanol
	Multi-step reaction with 2 steps 1: 1,2-dichloro-ethane / 0 °C 2: ammonia / methanol / 16 h / 0 - 4 °C

Reference： [1]Haynes et al. [Journal of the Chemical Society, 1957, p. 3727,3731]
[2]Current Patent Assignee: REJUVENATION THERAPEUTICS - WO2017/218580, 2017, A1

5
[ 98-92-0 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetonitrile 2: NH₃; methanol
	Multi-step reaction with 4 steps 1.1: 1,1,1,3,3,3-hexamethyl-disilazane / 130 °C 1.2: 0.5 h 2.1: sodium hydrogencarbonate; sodium dithionite / water / 0.33 h / Inert atmosphere 3.1: methanol; sodium hydroxide / 0.5 h 4.1: ammonium chloride / water / 1 h / 20 °C
	Multi-step reaction with 3 steps 1.1: acetonitrile 1.2: 0.5 h / 20 °C 2.1: methanol; sodium methylate / 0.5 h / 3 - 5 °C 3.1: sodium hydroxide; sodium chloride / water / 20 °C

	Multi-step reaction with 3 steps 1: 1,1,1,3,3,3-hexamethyl-disilazane / 5 h / Reflux 2: 1,2-dichloro-ethane / 0 °C 3: ammonia / methanol / -20 °C
	Multi-step reaction with 3 steps 1.1: ammonium sulfate / 8 h / 125 °C 2.1: tin(IV) chloride / dichloromethane / 1.5 h / 55 °C 2.2: 0.75 h / 0 °C 3.1: methanol; propylamine / 22 h / -5 °C
	Multi-step reaction with 2 steps 1: acetonitrile / 0.33 h / 20 °C / 760.05 Torr / Molecular sieve; Sealed tube 2: hydrogenchloride / methanol; ethanol / 760.05 Torr / Cooling; Sealed tube

Reference： [1]Haynes et al. [Journal of the Chemical Society, 1957, p. 3727,3731]
[2]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST - WO2015/14722, 2015, A1
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2015/186068, 2015, A1
[4]Current Patent Assignee: REJUVENATION THERAPEUTICS - WO2017/218580, 2017, A1
[5]Current Patent Assignee: SHANGHAI SHUZE BIOLOGICAL TECH RESEARCH INSTITUTE - CN111647032, 2020, A
[6]Haase, Robert; Hery-Barranco, Adrian; Pala, Laura; Parris, Jaclyn; Schabert, Günter; Spingler, Bernhard; Spitz, Urs [Molecules, 2021, vol. 26, # 9]

6
[ 19132-12-8 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With ammonium chloride In water at 20℃; for 1h;	3A Example 3(A); Preparation of nicotinamide riboside, chloride salt (the 13-anomer form of which isshown in Figure 5). A compound of formula (II), namely NRH (reduced nicotinamide riboside, shown in Figure 2; 50mg, 0.20mmol, leq), was dissolved in 5mL H20 and then ieq (i.e. 0.20mmol) of ammonium chloride was added in one portion. Activated charcoal (-10mg, i.e. 0.8Ommol) was then added and the mixturestirred at RT for -1 hr and then filtered and freeze-dried to give the chloride salt of nicotinamide riboside, quantitatively, i.e. 100% conversion and pure product.1H-NMR (D20, 400MHz) - ö 9.46 (s, 1H, aromatic), 9.12 (dt, 1H, J=6.3, 1.4 Hz, aromatic), 8.83 (dt, IH, J=8.2, 1.4 Hz, aromatic), 8.13 (dd, 1H, J=8.2, 6.3 Hz, aromatic>, 6.13 (d, 1H, J=4.3 Hz, H-i (anomeric)), 4.37 (t, 1H, J=4.7Hz, H-2), 4.31-4.34 (m, 1H, H-4), 4.21 (t, 1H, J=4.7Hz, H-3), 3.90(ABX, iH, Jaa13.0 Hz, Jab=3.5 Hz, H-5), 3.75 (ABX, 1H, Jaa=13.0 Hz, Jab=2.8 Hz, H-5).
89%	With 5%-palladium/activated carbon; ammonium chloride In isopropyl alcohol at 20℃; for 20h; Green chemistry;	1-4; 1-2 Example 1. Preparation and purification of crude nicotinamide riboside salt Dissolve 50 g of compound B in 500 mL of isopropanol, then add 10 g of ammonium chloride, 1 g of 5% palladium on carbon (wet product, water content of about 50%), ventilate the air, control the pressure to about 0.2 MPa, and stir at 20 ° C The reaction, about 20 hours, was monitored until the reaction was complete. The palladium-carbon was removed by filtration, and the filtrate was decolorized by adding activated carbon, and concentrated under reduced pressure. The obtained crude product was added with 500 mL of ethanol, stirred for crystallization, suction filtered, and the filter cake was dried.50 g of nicotinamide riboside chloride solid was obtained with a yield of 89% and a purity of 99.4%.

Reference： [1]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST - WO2015/14722, 2015, A1 Location in patent: Page/Page column 21
[2]Current Patent Assignee: 2Y CHEM - CN110283221, 2019, A Location in patent: Paragraph 0048-0060; 0064-0067

7
3-carbamoyl-1-((2R,3R,4R,5R)-3,4-diacetoxy-5-(acetoxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium trifluoromethanesulfonate [ No CAS ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
2%	With hydrogenchloride In methanol; ethanol Cooling; Sealed tube;	Example 15c: Deacetylation using hydrochloric acid and neutralization using triethylamine 8.00 g (15.1 mmol) of nicotinamide-2,3,5-tri-O-acetyl-β-D-ribofuranoside triflate were dissolved in 32 mL of methanol while stirring. 5.5 mL (31 mmol, 2 eq) of a 5.6 M solution of hydrogen chloride in ethanol were added while cooling. The resulting colorless solution was stirred at RT overnight. Control by thin-layer chromatography revealed complete deacylation and some nicotinamide impurities. The solution was divided into two halves.Isolation of the formed intermediate chloride: One half of the solution (20.5 mL) was seeded withnicotinamide-β-D-ribofuranoside chloride and stirred at room temperature. After about 2 h, a very thin suspension was formed, which was stored overnight in the refrigerator. The thin suspension was filtered, the residue was washed with ethanol and subsequently dried in vacuo at 30 °C. Only 0.05 g (2%) of a white crystalline powder of nicotinamide-beta-D-ribofuranoside chloride were obtained. Mp. 104 °C.
	Multi-step reaction with 3 steps 1: sodium hydrogencarbonate; sodium dithionite / water / 0.33 h / Inert atmosphere 2: methanol; sodium hydroxide / 0.5 h 3: ammonium chloride / water / 1 h / 20 °C
	Multi-step reaction with 2 steps 1: ammonia / methanol / 24 h / -9 - -8 °C 2: hydrogenchloride / methanol / 8 h / -8 - 0 °C

Reference： [1]Haase, Robert; Hery-Barranco, Adrian; Pala, Laura; Parris, Jaclyn; Schabert, Günter; Spingler, Bernhard; Spitz, Urs [Molecules, 2021, vol. 26, # 9]
[2]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST - WO2015/14722, 2015, A1
[3]Current Patent Assignee: Zhang Hongxi - CN108774278, 2018, A

8
[(2R,5R)-3,4-diacetoxy-5-(3-carbamoyl-4H-pyridin-1-yl)tetrahydrofuran-2-yl]methyl acetate [ No CAS ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: methanol; sodium hydroxide / 0.5 h 2: ammonium chloride / water / 1 h / 20 °C

Reference： [1]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST - WO2015/14722, 2015, A1

9
3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium trifluoromethanesulfonate [ No CAS ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium chloride; sodium hydroxide In water at 20℃;	2 EXAIVIPLE 2: Preparation of nicotinamide riboside chloride by ion exchange from nicotinamide riboside trifluoromethane sulfonate and acetate to chloride. The residue was transferred back into the 20 L reactor with 7.5 L of methanol. An ice bath was applied to the reactor to adjust the internal temperature to 3 °C. Separately, 3.75 L (3.75 mol) of 1M NaOCH3 in methanol was cooled to 3 °C, then this solution wasadded to the reactor over 10 minutes. The internal temperature was maintained below 5 °C during the addition. After addition was complete, the reaction was stirred for 30 mm, then 1.25 L (3.75 mol) of 3M HC1 was added slowly, keeping the internal temperature below 5 °C. At the end of the HC1 addition the pH = 3. The solvent was removed in vacuo. (For convenience, the partially concentrated solution could be stored at 4 °C for up to 48 h. After concentration was complete, the residue could be stored at -20 °C for up to 18 h. To remove the residual methanol, the evaporation residue was dissolved in water andconcentrated in vacuo (3 x 1 L). The residue was taken up in 5 L of water, and adjusted to pH = 4 with 2M NaOH(aq.). Sodium chloride (NaC1) was added to the solution, and the mixture was stirred at ambient temperature until saturated with NaC1, leaving about 5 g of undissolved NaC1. The saturated solution was extracted with tetrahydrofuran (THF, 3 x 5L). The aqueous layer was monitored by ‘H NIVIR to confirm that acetic acid was removedafter the extractions were complete.The aqueous phase was adjusted to pH = 6 - 7 with 2M NaOH(aq.), then extracted with THF (4 x 5 L). The aqueous layer was monitored by ‘H NIVIR to confirm that the residual nicotinamide was < 5 mol% relative to nicotinamide riboside. ‘9F NMR was also used to confirm the absence of trifluoromethanesulfonate in the aqueous layer. Theaqueous layer was then concentrated in vacuo to remove 2.5 L of water. The remaining suspension was diluted with 5 L of ethanol, filtered, and the salt precipitate was washed with 2.5 L of ethanol. The combined filtrate and washings solution was concentrated in vacuo to a thick oil. This was stirred with 1.5 L of methanol, the precipitate was filtered, and the solution was concentrated in vacuo. The residue was stirred with another 1.5 L ofmethanol, the precipitate was filtered, and the solution was concentrated in vacuo. The residue was stirred with a third 1.5 L portion of methanol, the precipitate was filtered, and the solution was concentrated in vacuo to give 385 g of a red-orange oil. The amount of residual methanol was determined to be 34 g by ‘H NMR, for a crude yield of 351 g (77%).The THF extractions served to remove most of the excess nicotinamide. Becausesodium trifluoromethanesulfonate is soluble in THF, the extractions also removed sodiumtrifluoromethanesulfonate from the solution, while leaving nicotinamide riboside in the aqueous layer with a chloride counterion. This allowed for the preparation of anomerically pure nicotinamide riboside chloride, in contrast to previous syntheses of nicotinamide riboside chloride, which delivered anomeric mixtures of nicotinamide riboside chloride(Jarman, M. Ross, W. C. J. J. Chem. Soc. (C) 1969, 199-203; Haynes, L. J.; Hughes, N. A.; Kenner, G. W.; Todd, A. J. Chem. Soc. 1957, 3727-3732). More recent syntheses of nicotinamide riboside have delivered anomerically pure material as either the bromide, trifluoromethanesulfonate or trifluoroacetate salts, which are less desirable for human consumption than the chloride.
16 g	With hydrogenchloride In methanol at -8 - 0℃; for 8h;	1-C The crude product was added to methanol (100 ml) solution and the temperature was lowered to -8 ° C. 28% hydrogen chloride in methanol solution (6 ml) was added dropwise, and the mixture was beaten for 4 hours. The mixture was filtered to obtain a beaten solid. The beaten once solid was added to methanol (100 ml) cool to -8 ° C. Add 28% hydrogen chloride methanol solution (3ml), beat for 4h, filter to obtain wet product, vacuum drying at room temperature for 24h, the beating temperature is 0 ° C (the first beating temperature and the second beating temperature are the same), get nicotinamide nucleoside chloride compound (16g, 55%).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2015/186068, 2015, A1 Location in patent: Page/Page column 73; 74; 75
[2]Current Patent Assignee: Zhang Hongxi - CN108774278, 2018, A Location in patent: Paragraph 0026; 0028; 0029; 0030; 0032; 0034

10
[ 23111-00-4 ]
sodium β-nicotinamide mononucleotide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	Stage #1: 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium (β-D-nicotinamide riboside) With trichlorophosphate for 1h; Milling; Stage #2: With sodium hydroxide In water	1 EXAMPLE 1 Synthetic preparation of Nicotinamide mononucleotide (NMN): To a dry 35 mL PTFE milling vessel containing one PTFE ball (0.8 cm diameter) was added nicotinamide riboside chloride (2000 mg, 6.88 mmol, 1.0 eq) and POC13 (2.57 mL, 27.52 mmol, 4.0 eq). The reaction was then milled at 30 Hz for 60 minutes or until the reaction had reached 95% conversion via c-18 HPLC analysis. The gum-like, gum-coated ball was removedand placed into a wide-necked flask, and the residue was solubilized in a minimal volume of distilled water over ice. The solution was adjusted to pH 6.0 by the drop-wise addition of a 2M NaOH solution. The aqueous solution was then reduced to a small volume under high vacuum and the pH was then adjusted to pH 3.0 using dilute nitric acid. To the aqueous solution was then added acetone (ca. 300 mL) and the precipitated white solid was separated and thesupernatant discarded. The mixture was solubilized in a minimal quantity of distilled water and was purified on a 400 g C-i 8 snap cartridge at a flow rate of 50 mL/min using Biotage column chromatography (100% H20). The purified fractions were then freeze-dried to yield the pure product in 23% isolated yields as the monosodium salt.[0233] ‘HNMR(400IVIHz, D20) öppm 9.32(1H, s, Ar), 9.13 (1H, app. d, Ar), 8.89(1H, dt,J=8.0, 1.3 Hz, Ar), 8.19 (1H, dd, J= 8.0, 6.5 Hz, Ar), 6.04 (1H, d, J= 5.5 Hz, H-i), 4.54 (1H, m,H-2), 4.46 (1H, t, J= 5.1 Hz, H-3), 4.34 (1H, dd, J= 5.0, 2.5 Hz, H-4), 4.21 (1H, ABX, J =12.0, 4.0 Hz, H-5), 4.05 (1H, ABX, Jab = 12.0, 4.0 Hz, H-5). ‘3C NIVIR (75 MHz, D20) ö ppm165.6 (C(=O)NH2), 146.0, 142.5, 139.9, 133.9, 128.5, 99.9 (C-i, anomeric), 89.4 (C-4), 77.7 (C-2), 70.9 (C-3), 64.1 (C-5). 31P NIVIR (162 MHz, D20) ö ppm 0.03. HRIVIS (ES, M + H)calculated for C11H14N208P 357.0488, found 357.047.
	Multi-step reaction with 3 steps 1: pyridine / acetonitrile / 12 h / 0 - 5 °C 2: platinum(IV) oxide; hydrogen / deuteromethanol / 12 h 3: sodium carbonate / water

Reference： [1]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST; CHROMADEX CORP. - WO2016/196941, 2016, A1 Location in patent: Paragraph 0231; 0232; 0233; 0234; 0235; 0236; 0237-0242
[2]Current Patent Assignee: WUHAN YIRUO BIO MAT - CN110845548, 2020, A

11
[ 64761-29-1 ]
[ 23111-00-4 ]
C₂₁H₂₅N₂O₅⁽¹⁺⁾*Cl^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26.6%	With CSA In N,N-dimethyl-formamide at 20℃; for 4h;	7 To a stirred suspension of Int. 17 (1 g, 3.92 mmol) in dry DMF (40 mL), mesitaldehyde dimethyl acetal (Int. 16) (2.28 g, 11.75 mmol) was added followed by cat. CSA (10 mg) at room temperature. After 30 minutes the reaction mixture became a clear solution and after 1 h white precipitation was observed. The resulting mixture was stirred at room temperature for 4 h, the reaction mixture was filtered and the precipitate was washed with diethyl ether (2 x 10 mL) and dried under vacuum to afford Int. 18 (400 mg, 26.6% yield) as a white solid. (0312) LC-MS: m/z: 385.79 [M]+ (0313) 1H NMR (400 MHz, DMSO-d6): δ 9.46 (s, 1H), 9.34 (d, J = 6.0 Hz, 1H), 9.08 (d, J = 8.0, 1H), 8.89 (brs, 1H, -NH), 8.27 (t, J = 6.8 Hz 1H), 8.17 (brs, 1H, -NH), 6.89 (s, 2H), 6.69 (s, 1H), 6.21 (s, 1H), 5.43 (d, J = 6.4 Hz, 2H), 5.0 (d, J = 6.8 Hz, 1H), 4.96 (brs, 1H, -OH), 3.77- 3.66 (m, 2H), 2.42 (s, 6H), 2.24 (s, 3H).

Reference： [1]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2017/79195, 2017, A1 Location in patent: Page/Page column 45

12
C₂₃H₃₇N₂O₈Si₂⁽¹⁺⁾*Cl^(1-) [ No CAS ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia In methanol at -20℃;	4 Example 4. Preparation of nicotinamide riboside chloride salt of Formula (1) The crude compound (4a) is quickly dissolved in dry methanol saturated with dry ammonia and stirred at -20 °C until the reaction is complete. The solvents are removed under vacuum, and the crude product is partitioned between methanol and hexane. The hexane layer is discarded and product is precipitated from the methanol layer by the addition of dry ethyl acetate. The collected product is washed with ethyl acetate and dried to give highly hygroscopic powder, which is stored as needed under suitable anhydrous conditions.

Reference： [1]Current Patent Assignee: REJUVENATION THERAPEUTICS - WO2017/218580, 2017, A1 Location in patent: Paragraph 0089

13
C₁₉H₂₄NO₉⁽¹⁺⁾*Cl^(1-) [ No CAS ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia In methanol at 0 - 4℃; for 16h;	6 Example 6. Preparation of nicotinamide riboside chloride salt of Formula (1) The crude compound of Formula (4b) is dissolved in 1.0 mL of 4 NNH3/MeOH at 0 °C, and stirred at 4 °C for 16 hours. The mixture is concentrated and coevaporated several times with MeOH to remove residual ammonia. The residue is suspended in ethyl acetate, filtered, and washed with dry ethyl acetate. The resulting solid is dissolved in methanol, and the resulting solution is extracted with hexane. The methanol layer is then separated and concentrated, and the product is then precipitated by treatment with dry ethyl acetate or dry ether.

Reference： [1]Current Patent Assignee: REJUVENATION THERAPEUTICS - WO2017/218580, 2017, A1 Location in patent: Paragraph 0091

14
[ 109527-15-3 ]
[ 72521-19-8 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
20 % de	With ammonia In methanol at 0℃; for 3h; Inert atmosphere; Overall yield = 0.229 g;	10 Example 10. Preparation of nicotinamide riboside chloride salt (Formula (I)) To a 0°C solution of crude compound (4a) (prepared in Example 9, 850 mg, 2.04 mmol) in anhydrous methanol (10.1 mL), saturated ammonia in anhydrous methanol (7 M, 13.1 mL) was added. The reaction mixture was stirred for 3 h at 0°C under an inert atmosphere and monitored by TLC. The solvent was removed immediately in vacuo and the isolated residue co-evaporated one additional time with anhydrous methanol (10 mL). The crude residue was dissolved in minimal amounts of anhydrous methanol and extracted with hexane. The product was precipitated out of the methanol layer by the addition of anhydrous ethyl acetate. The solids were collected by filtration and were washed with anhydrous ethyl acetate to provide a compound of formula (I) as an orange solid (0.229 g, 3 8.6% yield). ‘H-NMR: a 60:40 mixture of f3:ci. isomers based on the chemical shift (6.30 ppm vs. 6.60 ppm) of the proton on the anomeric carbon. MS: mass calculated for C11H15N2O5: 255.10; found (mlz): positive: 255.3 (M)t TLC: n-butanol/water/acetic acid (5:3:2) gives Rf = 0.36.HPLC: peaks at 1.99, 2.54, 2.84, 3.78, and 4.12 minutes. HPLC Conditions:column: Agilent SB-C 18 Poroshell 120, 4.6 x 150 mm, 2.7 jtm, solvent A: 25 mM ammonium acetate in water, solvent B: acetonitrile, flow rate: 9 ml/min, gradient: 5%solvent B for 0.5 minutes, to 95% solvent B over 6 minutes, 95% solvent B for 2.5 minutes, to 5% solvent B over 1 minute.

Reference： [1]Current Patent Assignee: REJUVENATION THERAPEUTICS - WO2017/218580, 2017, A1 Location in patent: Paragraph 0101-0104

15
[ 40554-98-1 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetonitrile / 0.33 h / 70 °C 2: hydrogenchloride / methanol / 12 h / Sealed tube
	Multi-step reaction with 2 steps 1: acetonitrile / 50 °C 2: hydrogenchloride / methanol / 12 h / Sealed tube

Reference： [1]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST; CHROMADEX CORP. - US2018/134743, 2018, A1
[2]Current Patent Assignee: THE QUEEN'S UNIVERSITY OF BELFAST; CHROMADEX CORP. - US2018/134743, 2018, A1

16
[ 78687-39-5 ]
[ 23111-00-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	With Amberlite IRA-402 (Cl-Form) In water for 8h;	3 Example 3: Preparation of nicotinamide^-D-ribofuranoside chloride of formula O- Ib [00170] 25 g of the product obtained in Example 2 were dissolved in 140 ml water and 140 g of ion exchange resin Amberlite IRA-402 (Cl-Form) were added and stirred for two hours. The resin was removed by filtration and washed with 140 ml water. To the filtrate were added 105 g of ion exchange resin, again stirred for two hours, filtered and washed with 40 ml water. This exchange was repeated further two times using 105 g of ion exchanger each. The final filtrate was evaporated to give 21.8 g of a clear, pale yellow resin. This resin was dissolved in a hot mixture of 100 ml ethanol and 100 ml methanol. The crystals obtained after cooling in an ice bath were filtered, washed with isopropanol and dried to give 12.8 g (59 %) of the title compound as colorless crystals. The bromide content was below 0.1 %. Mp: 123-124 °C.1H-NMR (400 MHz, D20): 3.84 (dd, 1 H, H5’), 3.98 (dd, 1 H, H5’), 4.30 (t, 1 H, H3’), 4.40- 4.47 (m, 2H, H4’, H2’), 6.19 (d, 1 H, H1’), 8.22 (t, 1 H, H5), 8.92 (d, 1 H, H4), 9.21 (d, 1 H, H6), 9.54 (s, 1 H, H2);13C-NMR (100 MHz, D20): 60.3 (C5‘), 69.8 (C3‘), 77.5 (C2‘), 87.7 (C4‘), 99.9 (C1‘), 128.5 (C5), 134.0 (C3), 140.4 (C2), 142.7 (C6), 145.7 (C4), 165.8 (CONH2).

Reference： [1]Current Patent Assignee: KKR & CO LP - WO2019/219895, 2019, A1 Location in patent: Paragraph 00170

17
[ 23111-00-4 ]
[ 2524-64-3 ]
C₂₃H₂₄N₂O₈P⁽¹⁺⁾*Cl^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine In acetonitrile at 0 - 5℃; for 12h;	1.a; 2.a; 3.a; 4.a a. Esterification reaction, the reaction formula is as follows: Under ice water bath, add 87g pyridine and 290g nicotinamide ribose to 500mL acetonitrile,The temperature was controlled at 0-5 ° C, and then 281 g of diphenyl chlorophosphate was slowly added dropwise. After the addition was completed, the reaction was continued for about 12 hours under stirring until the reaction was complete (see the disappearance of the raw material spot on the TLC spot). After the reaction, the acetonitrile was recovered under reduced pressure at 40-45 ° C,The crude product of β-nicotinamide ribose intermediate nicotinamide ribose diphenyl phosphate was about 630 g, and the yield was 100%.

Reference： [1]Current Patent Assignee: WUHAN YIRUO BIO MAT - CN110845548, 2020, A Location in patent: Paragraph 0047-0051; 0058-0061; 0067-0070; 0077-0080

18
[ 23111-00-4 ]
[ 77-76-9 ]
C₁₄H₁₉N₂O₅⁽¹⁺⁾*HO₄S^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With fuming sulphuric acid In acetonitrile at 0 - 20℃; for 2h; Inert atmosphere;