[ CAS No. 137618-48-5 ] {[proInfo.proName]}

Name: 137618-48-5|tert-Butyl (2,3-dihydroxypropyl)carbamate|95%
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Quality Control of [ 137618-48-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 137618-48-5 ]

Product Details of [ 137618-48-5 ]

CAS No. :	137618-48-5	MDL No. :	MFCD01321265
Formula :	C₈H₁₇NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OWAMQHJPVUGZSB-UHFFFAOYSA-N
M.W :	191.22	Pubchem ID :	4206999
Synonyms :

Calculated chemistry of [ 137618-48-5 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.88
Num. rotatable bonds :	6
Num. H-bond acceptors :	4.0
Num. H-bond donors :	3.0
Molar Refractivity :	47.41
TPSA :	78.79 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.73 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.75
Log Po/w (XLOGP3) :	-0.37
Log Po/w (WLOGP) :	-0.14
Log Po/w (MLOGP) :	-0.2
Log Po/w (SILICOS-IT) :	-0.32
Consensus Log Po/w :	0.15

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.4
Solubility :	76.7 mg/ml ; 0.401 mol/l
Class :	Very soluble
Log S (Ali) :	-0.82
Solubility :	28.8 mg/ml ; 0.151 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.54
Solubility :	54.9 mg/ml ; 0.287 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.78

Safety of [ 137618-48-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 137618-48-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 137618-48-5 ]
Downstream synthetic route of [ 137618-48-5 ]

[ 137618-48-5 ] Synthesis Path-Upstream 1~7

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Yield	Reaction Conditions	Operation in experiment
56%	With sodium periodate In water at 20℃; for 2 h;	Step 2 tert-Butyl 2-oxoethylcarbamate: Sodium periodate (41.52 g; 194 mmol; 1.00 equiv) was added in several batches to tert-butyl 2,3-dihydroxypropylcarbamate (37 g; 194 mmol; 1.00 equiv) dissolved in water (300 mL). The resulting solution was stirred at ambient temperature for about 2 hours. The solids were were removed by filtration. Standard extractive workup with dichloromethane, gave the title product as a white solid (17 g; 56percent yield). 1H NMR (300 MHz, CDCl3) δ 9.65 (s, 1H), 5.26 (s, 1H), 4.07 (d, J=4.5 Hz, 2H), 1.46 (s, 9H).

Reference： [1] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 2, p. 445 - 451
[2] Journal of the American Chemical Society, 2015, vol. 137, # 39, p. 12442 - 12445
[3] Journal of the American Chemical Society, 2005, vol. 127, # 10, p. 3339 - 3345
[4] Patent: US2010/9950, 2010, A1, . Location in patent: Page/Page column 24
[5] Patent: US6750348, 2004, B1, . Location in patent: Page column 66
[6] Journal of Medicinal Chemistry, 2014, vol. 57, # 11, p. 4969 - 4974
[7] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 20, p. 4509 - 4512
[8] Patent: WO2018/175927, 2018, A2, . Location in patent: Paragraph 00303

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Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride; sodium hydroxide In water; ethyl acetate	(a) Preparation of (bocamino) acetaldehyde 3-Amino-1,2-propanediol(80.0 g; 0.88 mol) was dissolved in water (1500 ml) and the solution was cooled to 4° C., whereafter Boc anhydride (230 g; 1.05 mol) was added at once. The solution was gently heated to room temperature with a water bath. The pH was kept at 10.5 by the dropwise addition of sodium hydroxide. Over the course of the reaction a total of 70.2 g NaOH, dissolved in 480 ml water, was added. After stirring overnight, ethyl acetate (1000 ml) was added and the mixture was cooled to 0° C. and the pH was adjusted to 2.5 by the addition of 4M hydrochloric acid. The ethyl acetate layer was removed and the acidic aqueous solution was extracted with more ethyl acetate (8500 ml). The combined ethyl acetate solution was reduced to a volume of 1500 ml using a rotary evaporator. The resulting solution was washed with half saturated potassium hydrogen sulphate (1500 ml) and then with saturated sodium chloride. It then was dried over magnesium sulphate and evaporated to dryness, in vacuo. Yield. 145.3 g (86percent) 3-Bocamino-1,2-propanediol (144.7 g; 0.757 mol) was suspended in water (750 ml) and potassium periodate (191.5 g; 0.833 mol) was added. The mixture was stirred under nitrogen for 2.5 h and the precipitated potassium iodate was removed by filtration and washed once with water (100 ml). The aqueous phase was extracted with chloroform (6400 ml). The chloroform extracts were dried and evaporated to dryness, in vacuoo Yield 102 g (93percent) of an oil. The (bocamino)acetaldehyde was purified by kugelrohr distillation at 84° C. and 0.3 mmHg in two portions. The yield 79 g (77percent) of a colorless oil.
93%	With hydrogenchloride; sodium hydroxide In water; ethyl acetate	(a) Preparation of (bocamino)acetaldehyde 3-Amino-1,2-propanediol(80.0 g; 0.88 mol) was dissolved in water (1500 ml) and the solution was cooled to 4° C., whereafter Boc anhydride (230 g; 1.05 mol) was added at once. The solution was gently heated to room temperature with a water bath. The pH was kept at 10.5 by the dropwise addition of sodium hydroxide. Over the course of the reaction a total of 70.2 g NaOH, dissolved in 480 ml water, was added. After stirring overnight, ethyl acetate (1000 ml) was added and the mixture was cooled to 0° C. and the pH was adjusted to 2.5 by the addition of 4 M hydrochloric acid. The ethyl acetate layer was removed and the acidic aqueous solution was extracted with more ethyl acetate (8500 ml). The combined ethyl acetate solution was reduced to a volume of 1500 ml using a rotary evaporator. The resulting solution was washed with half saturated potassium hydrogen sulphate (1500 ml) and then with saturated sodium chloride. It then was dried over magnesium sulphate and evaporated to dryness, in vacuo. Yield. 145.3 g (86percent) 3-Bocamino-1,2-propanediol (144.7 g; 0.757 mol) was suspended in water (750 ml) and potassium periodate (191.5 g; 0.833 mol) was added. The mixture was stirred under nitrogen for 2.5 h and the precipitated potassium iodate was removed by filtration and washed once with water (100 ml). The aqueous phase was extracted with chloroform (6400 ml). The chloroform extracts were dried and evaporated to dryness, in vacuo. Yield 102 g (93percent) of an oil. The (bocamino)acetaldehyde was purified by kugelrohr distillation at 84° C. and 0.3 mmHg in two portions. The yield 79 g (77percent) of a colorless oil.

Reference： [1] Patent: US5539082, 1996, A,
[2] Patent: US6228982, 2001, B1,

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[ 616-30-8 ]
[ 24424-99-5 ]
[ 137618-48-5 ]
[ 89711-08-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride; sodium hydroxide In water; ethyl acetate	(a) Preparation of (bocamino)acetaldehyde 3-Amino-1,2-propanediol (80.0 g; 0.88 mol) was dissolved in water (1500 ml) and the solution was cooled to 4° C., whereafter Boc anhydride (230 g; 1.05 mol) was added at once. The solution was gently heated to room temperature with a water bath. The pH was kept at 10.5 by the dropwise addition of sodium hydroxide. Over the course of the reaction a total of 70.2 g NaOH, dissolved in 480 ml water, was added. After stirring overnight, ethyl acetate (1000 ml) was added and the mixture was cooled to 0° C. and the pH was adjusted to 2.5 by the addition of 4 M hydrochloric acid. The ethyl acetate layer was removed and the acidic aqueous solution was extracted with more ethyl acetate (8500 ml). The combined ethyl acetate solution was reduced to a volume of 1500 ml using a rotary evaporator. The resulting solution was washed with half saturated potassium hydrogen sulphate (1500 ml) and then with saturated sodium chloride. It then was dried over magnesium sulphate and evaporated to dryness, in vacuo. Yield. 145.3 g (86percent) 3-Bocamino-1,2-propanediol (144.7 g; 0.757 mol) was suspended in water (750 ml) and potassium periodate (191.5 g; 0.833 mol) was added. The mixture was stirred under nitrogen for 2.5 h and the precipitated potassium iodate was removed by filtration and washed once with water (100 ml). The aqueous phase was extracted with chloroform (6400 ml). The chloroform extracts were dried and evaporated to dryness, in vacuo. Yield 102 g (93percent) of an oil. The (bocamino)acetaldehyde was purified by kugelrohr distillation at 84° C. and 0.3 mmHg in two portions. The yield 79 g (77percent) of a colorless oil.

Reference： [1] Patent: US6713602, 2004, B1,

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Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydroxide In <i>tert</i>-butyl alcohol at 0 - 20℃; for 5 h;	3 g (1.0 eq., 32.93 mmol) of the 3-amino-1,2-propane diol 23 was dissolved in 20 mL of tert-BuOH and 20 mL of 1 M NaOH, and under ice cooling, added with 20 mL of tert-BuOH solution containing 7.19 g (1.0 eq., 32.93 mmol) of Boc₂O. After that, it was stirred for 5 hours at room temperature. After confirming by TLC the disappearance of the reacting materials, it was concentrated under reduced pressure by using an evaporator in water bath at 50° C. Then, the reaction solution was neutralized by using 1 M HCl. Liquid fractionation extraction of the neutralized solution was performed 3 times by adding ethyl acetate and water, and the collected organic layer was washed with a saturated aqueous solution of NaCl. After drying over magnesium sulfate, it was concentrated under reduced pressure by using an evaporator in water bath at 40° C. As a result, the desired compound 2 was obtained in an amount of 6.3 g (yield: quant.). ¹H-NMR signal assignment is given in the following.¹H-NMR (500 MHz, CDCl₃) δ1.45 (9H, s), 2.68-2.71 (1H, br), 2.75-2.81 (1H, br), 3.20 (2H, dd), 3.63 (2H, dd), 3.71 (1H, m) 4.91 (1H, br).
99%	With triethylamine In methanol at 20 - 50℃; for 1.33333 h;	1-aminopropane-2,3-diol (5 g, 55 mmol) was dissolved in methanol (200 ml) followed by dropwise addition of triethylamine (0.5 ml per mmol of amine) and di-tert-butyl dicarbonate [(BOC)2O] wherein BOC corresponds to tertbutyloxycarbonyl (17.97 g, 82 mmol). The reaction medium was heated at 40-50° C. for 20 min then stirred at room temperature for 1 hour. After evaporation of the solvent, the colorless oily residue was purified by chromatography on silica gel (eluent: dichloromethane/methanol 95:5) to give the desired compound in the form of a colorless oil which crystallized slowly. Yield: 99percent Rf (dichloromethane/methanol 9:1): 0.39 IR: νNH 3350 cm^-1; νCO ester 1746 cm^-1; νCO amide 1682 cm^-1MP<15° C. NMR (1H, CDCl₃):1.44 (s, 9H, CH₃(BOC)); 3.16-3.31 (m, 2H, BOCNH-CH₂-CH-CH₂-OH); 3.44 (multiplet, 2H, OH); 3.16-3.31 (m, 2H, BOCNH-CH₂-CH-CH₂-OH); 3.71-3.78 (m,1H, BOCNH-CH₂-CH-CH₂-OH); 5.24 (m, 1H, -NHBOC). MS (MALDI-TOF): M+23=214 (M+Na⁺)
99%	With triethylamine In methanol at 20 - 50℃; for 1.33333 h;	Example 22; Preparation of 1-amino-2,3-di(tetradecylthioacetylthio)propane hydrochloride; Preparation of 1-(tert-butyloxycarbonylamino)propane-2,3-diol (example 22a); 1-aminopropane-2,3-diol (5 g, 55 mmol) was dissolved in methanol (200 ml) followed by dropwise addition of triethylamine (0.5 ml per mmol of amine) and di-tert-butyl dicarbonate [(BOC)2O] (wherein BOC corresponds to tertbutyloxycarbonyl) (17.97 g, 82 mmol). The reaction medium was heated at 40-50° C. for 20 min then stirred at room temperature for 1 hour. After evaporation of the solvent, the colorless oily residue was purified by chromatography on silica gel (eluent : dichloromethane/methanol 95:5) to give the desired compound in the form of a colorless oil which crystallized slowly. Yield: 99percent Rf (dichloromethane/methanol 9:1): 0.39 IR: vNH 3350 cm^-1; vCO ester 1746 cm^-1; vCO amide 1682 cm^-1MP<15° C. NMR (¹H, CDCl₃): 1.44 (s, 9H, CH₃(BOC)); 3.16-3.31 (m, 2H, BOCNH-CH₂-CH-CH₂-OH); 3.44 (multiplet, 2H, OH); 3.16-3.31 (m, 2H, BOCNH-CH₂-CH-CH₂-OH); 3.71-3.78 (m, 1H, BOCNH-CH₂-CH-CH₂-OH); 5.24 (m, 1H, -NHBOC). MS (MALDI-TOF): M+23=214 (M+Na⁺)

99%	With triethylamine In methanol at 20 - 50℃; for 1.33333 h;	Preparation of 1-(tert-butyloxycarbonylamino)propane-2,3-diol (example 17a) 1-aminopropane-2,3-diol (5 g, 55 mmol) was dissolved in methanol (200 ml) followed by dropwise addition of triethylamine (0.5 ml per mmol of amine) and di-tert-butyl dicarbonate [(BOC)2O] wherein BOC corresponds to tertbutyloxycarbonyl (17.97 g, 82 mmol). The reaction medium was heated at 40-50° C. for 20 min then stirred at room temperature for 1 hour. After evaporation of the solvent, the colorless oily residue was purified by chromatography on silica gel (eluent:dichloromethane/methanol 95:5) to give the desired compound in the form of a colorless oil which crystallized slowly. Yield: 99percent Rf (dichloromethane/methanol 9:1): 0.39 IR: νNH 3350 cm^-1; νCO ester 1746 cm^-1; νCO amide 1682 cm^-1
97%	at 40℃; for 16 h;	Step 1 tert-Butyl 2,3-dihydroxypropylcarbamate: di-tert-Butyl dicarbonate (43.6 g; 200 mmol; 1.00 equiv) was added in several batches to a solution of 3-aminopropane-1,2-diol (18.2 g; 200 mmol; 1.00 equiv) in acetonitrile (200 mL). The mixture was stirred at about 40° C. for about 16 hours. The resulting mixture was concentrated in vacuo to give the title product as colorless oil (37 g; 97percent yield). LC-MS: m/z=192 (MH)⁺.
96%	With triethylamine In methanol at 20 - 50℃; for 12.33 h;	Intermediate A1A: tert-Butyl(2,3-dihydroxypropyl)carbamate The above Intermediate was synthesized according to a patent literature procedure reported in U.S. Publication No. 2006/69156 A1 (2006). To a solution of 3-aminopropane-1,2-diol (10.0 g, 110 mmol) in MeOH (407 mL) was added Boc₂O (35.9 g, 165 mmol) and TEA (55 mL, 395 mmol) and the reaction mixture was heated at 50° C. for 20 min., followed by stirring at room temperature for 12 h. The reaction was then concentrated under reduced pressure to provide a residue. It was purified by silica gel chromatography (330 g REDISEP® column, eluting with 5percent MeOH in DCM). Fractions containing the product were combined and evaporated to afford Intermediate A1A (20.14 g, 96percent) as a colorless oil. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 6.61 (br. s., 1H), 4.63 (d, J=4.9 Hz, 1H), 4.47 (t, J=5.6 Hz, 1H), 3.45 (d, J=5.6 Hz, 1H), 3.31-3.23 (m, 2H), 3.09-2.98 (m, 1H), 2.85 (d, J=6.6 Hz, 1H), 1.38 (s, 9H).
94%	With triethylamine In methanol; dichloromethane at 23℃;	(+/-)-3-amino-1,2-propanediol (11.29 g, 124 mmol) was dissolved in CH2Cl2:CH3OH (1:5) (1 M) and triethylamine (2 mL, 14.7 mmol) was added. Di-tert-butyl dicarbonate (32.5 g, 149 mmol) was dissolved in dichloromethane (0.8 M, 186 mL) and added slowly to the reaction mixture. The resulting reaction was stirred at 23 °C for 2 h, followed by TLC analysis that showed a full consumption of the starting material. The reaction mixture was evaporated under reduced pressure, and the residue was purified by column chromatography with EtOA/:Hexanes 1:4, then dried on high vacuum to yield 11 as a white solid (23.7 g, 94 percent yield). 1H NMR (500 MHz, CDCl3) δ 5.28 – 4.96 (m, 1H), 3.83 – 3.73 (m, 1H), 3.60 (qd, J = 11.7, 4.9 Hz, 2H), 3.44 (s, 1H), 3.27 (dt, J = 12.9, 6.0 Hz, 2H), 1.46 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 157.45 , 80.13 , 71.37 , 63.58, 28.35 , 27.42.

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 2, p. 623 - 627
[2] Patent: US2016/151506, 2016, A1, . Location in patent: Paragraph 0308-0312
[3] Canadian Journal of Chemistry, 1997, vol. 75, # 7, p. 942 - 948
[4] Patent: US2006/69156, 2006, A1, . Location in patent: Page/Page column 26
[5] Patent: US2006/154984, 2006, A1, . Location in patent: Page/Page column 41
[6] Patent: US2006/35977, 2006, A1, . Location in patent: Page/Page column 28
[7] Angewandte Chemie - International Edition, 2015, vol. 54, # 40, p. 11696 - 11700[8] Angew. Chem., 2015, vol. 127, # 40, p. 11862 - 11866,5
[9] Patent: US2010/9950, 2010, A1, . Location in patent: Page/Page column 23
[10] Patent: US9273058, 2016, B2, . Location in patent: Page/Page column 449; 453
[11] MedChemComm, 2017, vol. 8, # 11, p. 2050 - 2054
[12] Journal of Medicinal Chemistry, 2014, vol. 57, # 11, p. 4969 - 4974
[13] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 20, p. 4509 - 4512
[14] Journal of the American Chemical Society, 2015, vol. 137, # 39, p. 12442 - 12445
[15] Synthesis, 1998, # 8, p. 1113 - 1118
[16] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 2, p. 445 - 451
[17] Journal of the American Chemical Society, 2005, vol. 127, # 10, p. 3339 - 3345
[18] Chemical and Pharmaceutical Bulletin, 1991, vol. 39, # 8, p. 1972 - 1982
[19] Journal of Medicinal Chemistry, 2006, vol. 49, # 3, p. 1191 - 1197
[20] Chemistry - A European Journal, 2000, vol. 6, # 22, p. 4211 - 4217
[21] Patent: EP720615, 2000, B1,
[22] Patent: EP2119718, 2009, A1, . Location in patent: Page/Page column 84-85
[23] RSC Advances, 2013, vol. 3, # 19, p. 6771 - 6774
[24] Patent: WO2013/163675, 2013, A1, . Location in patent: Paragraph 00181
[25] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 5756 - 5763
[26] Patent: WO2016/206101, 2016, A1, . Location in patent: Page/Page column 193
[27] Patent: WO2018/175927, 2018, A2, . Location in patent: Paragraph 00299

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Reference： [1] Patent: US5539082, 1996, A,

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Reference： [1] Synlett, 2011, # 6, p. 821 - 825

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Reference： [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 3, p. 1191 - 1197
[2] Canadian Journal of Chemistry, 1997, vol. 75, # 7, p. 942 - 948
[3] Patent: WO2013/163675, 2013, A1,

[ 137618-48-5 ] Synthesis Path-Downstream 1~88

1
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[ 24424-99-5 ]
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Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydroxide; In tert-butyl alcohol; at 0 - 20℃; for 5h;	3 g (1.0 eq., 32.93 mmol) of the 3-amino-1,2-propane diol 23 was dissolved in 20 mL of tert-BuOH and 20 mL of 1 M NaOH, and under ice cooling, added with 20 mL of tert-BuOH solution containing 7.19 g (1.0 eq., 32.93 mmol) of Boc2O. After that, it was stirred for 5 hours at room temperature. After confirming by TLC the disappearance of the reacting materials, it was concentrated under reduced pressure by using an evaporator in water bath at 50 C. Then, the reaction solution was neutralized by using 1 M HCl. Liquid fractionation extraction of the neutralized solution was performed 3 times by adding ethyl acetate and water, and the collected organic layer was washed with a saturated aqueous solution of NaCl. After drying over magnesium sulfate, it was concentrated under reduced pressure by using an evaporator in water bath at 40 C. As a result, the desired compound 2 was obtained in an amount of 6.3 g (yield: quant.). 1H-NMR signal assignment is given in the following.1H-NMR (500 MHz, CDCl3) delta1.45 (9H, s), 2.68-2.71 (1H, br), 2.75-2.81 (1H, br), 3.20 (2H, dd), 3.63 (2H, dd), 3.71 (1H, m) 4.91 (1H, br).
99%	With triethylamine; In methanol; at 20 - 50℃; for 1.33333h;	1-aminopropane-2,3-diol (5 g, 55 mmol) was dissolved in methanol (200 ml) followed by dropwise addition of triethylamine (0.5 ml per mmol of amine) and di-tert-butyl dicarbonate [(BOC)2O] wherein BOC corresponds to tertbutyloxycarbonyl (17.97 g, 82 mmol). The reaction medium was heated at 40-50 C. for 20 min then stirred at room temperature for 1 hour. After evaporation of the solvent, the colorless oily residue was purified by chromatography on silica gel (eluent: dichloromethane/methanol 95:5) to give the desired compound in the form of a colorless oil which crystallized slowly. Yield: 99% Rf (dichloromethane/methanol 9:1): 0.39 IR: nuNH 3350 cm-1; nuCO ester 1746 cm-1; nuCO amide 1682 cm-1 MP<15 C. NMR (1H, CDCl3):1.44 (s, 9H, CH3 (BOC)); 3.16-3.31 (m, 2H, BOCNH-CH2-CH-CH2-OH); 3.44 (multiplet, 2H, OH); 3.16-3.31 (m, 2H, BOCNH-CH2-CH-CH2-OH); 3.71-3.78 (m,1H, BOCNH-CH2-CH-CH2-OH); 5.24 (m, 1H, -NHBOC). MS (MALDI-TOF): M+23=214 (M+Na+)
99%	With triethylamine; In methanol; at 20 - 50℃; for 1.33333h;	Example 22; Preparation of 1-amino-2,3-di(tetradecylthioacetylthio)propane hydrochloride; Preparation of 1-(tert-butyloxycarbonylamino)propane-2,3-diol (example 22a); 1-aminopropane-2,3-diol (5 g, 55 mmol) was dissolved in methanol (200 ml) followed by dropwise addition of triethylamine (0.5 ml per mmol of amine) and di-tert-butyl dicarbonate [(BOC)2O] (wherein BOC corresponds to tertbutyloxycarbonyl) (17.97 g, 82 mmol). The reaction medium was heated at 40-50 C. for 20 min then stirred at room temperature for 1 hour. After evaporation of the solvent, the colorless oily residue was purified by chromatography on silica gel (eluent : dichloromethane/methanol 95:5) to give the desired compound in the form of a colorless oil which crystallized slowly. Yield: 99% Rf (dichloromethane/methanol 9:1): 0.39 IR: vNH 3350 cm-1; vCO ester 1746 cm-1; vCO amide 1682 cm-1 MP<15 C. NMR (1H, CDCl3): 1.44 (s, 9H, CH3 (BOC)); 3.16-3.31 (m, 2H, BOCNH-CH2-CH-CH2-OH); 3.44 (multiplet, 2H, OH); 3.16-3.31 (m, 2H, BOCNH-CH2-CH-CH2-OH); 3.71-3.78 (m, 1H, BOCNH-CH2-CH-CH2-OH); 5.24 (m, 1H, -NHBOC). MS (MALDI-TOF): M+23=214 (M+Na+)

99%	With triethylamine; In methanol; at 20 - 50℃; for 1.33333h;	Preparation of 1-(tert-butyloxycarbonylamino)propane-2,3-diol (example 17a) 1-aminopropane-2,3-diol (5 g, 55 mmol) was dissolved in methanol (200 ml) followed by dropwise addition of triethylamine (0.5 ml per mmol of amine) and di-tert-butyl dicarbonate [(BOC)2O] wherein BOC corresponds to tertbutyloxycarbonyl (17.97 g, 82 mmol). The reaction medium was heated at 40-50 C. for 20 min then stirred at room temperature for 1 hour. After evaporation of the solvent, the colorless oily residue was purified by chromatography on silica gel (eluent:dichloromethane/methanol 95:5) to give the desired compound in the form of a colorless oil which crystallized slowly. Yield: 99% Rf (dichloromethane/methanol 9:1): 0.39 IR: nuNH 3350 cm-1; nuCO ester 1746 cm-1; nuCO amide 1682 cm-1
97%	In acetonitrile; at 40℃; for 16h;	Step 1 tert-Butyl 2,3-dihydroxypropylcarbamate: di-tert-Butyl dicarbonate (43.6 g; 200 mmol; 1.00 equiv) was added in several batches to a solution of 3-aminopropane-1,2-diol (18.2 g; 200 mmol; 1.00 equiv) in acetonitrile (200 mL). The mixture was stirred at about 40 C. for about 16 hours. The resulting mixture was concentrated in vacuo to give the title product as colorless oil (37 g; 97% yield). LC-MS: m/z=192 (MH)+.
96%	With triethylamine; In methanol; at 20 - 50℃; for 12.33h;	Intermediate A1A: tert-Butyl(2,3-dihydroxypropyl)carbamate The above Intermediate was synthesized according to a patent literature procedure reported in U.S. Publication No. 2006/69156 A1 (2006). To a solution of 3-aminopropane-1,2-diol (10.0 g, 110 mmol) in MeOH (407 mL) was added Boc2O (35.9 g, 165 mmol) and TEA (55 mL, 395 mmol) and the reaction mixture was heated at 50 C. for 20 min., followed by stirring at room temperature for 12 h. The reaction was then concentrated under reduced pressure to provide a residue. It was purified by silica gel chromatography (330 g REDISEP column, eluting with 5% MeOH in DCM). Fractions containing the product were combined and evaporated to afford Intermediate A1A (20.14 g, 96%) as a colorless oil. 1H NMR (400 MHz, DMSO-d6) delta ppm 6.61 (br. s., 1H), 4.63 (d, J=4.9 Hz, 1H), 4.47 (t, J=5.6 Hz, 1H), 3.45 (d, J=5.6 Hz, 1H), 3.31-3.23 (m, 2H), 3.09-2.98 (m, 1H), 2.85 (d, J=6.6 Hz, 1H), 1.38 (s, 9H).
94%	With triethylamine; In methanol; dichloromethane; at 23℃;	(+/-)-3-amino-1,2-propanediol (11.29 g, 124 mmol) was dissolved in CH2Cl2:CH3OH (1:5) (1 M) and triethylamine (2 mL, 14.7 mmol) was added. Di-tert-butyl dicarbonate (32.5 g, 149 mmol) was dissolved in dichloromethane (0.8 M, 186 mL) and added slowly to the reaction mixture. The resulting reaction was stirred at 23 C for 2 h, followed by TLC analysis that showed a full consumption of the starting material. The reaction mixture was evaporated under reduced pressure, and the residue was purified by column chromatography with EtOA/:Hexanes 1:4, then dried on high vacuum to yield 11 as a white solid (23.7 g, 94 % yield). 1H NMR (500 MHz, CDCl3) delta 5.28 - 4.96 (m, 1H), 3.83 - 3.73 (m, 1H), 3.60 (qd, J = 11.7, 4.9 Hz, 2H), 3.44 (s, 1H), 3.27 (dt, J = 12.9, 6.0 Hz, 2H), 1.46 (s, 9H). 13C NMR (126 MHz, CDCl3) delta 157.45 , 80.13 , 71.37 , 63.58, 28.35 , 27.42.
	With hydrogenchloride; sodium hydroxide; In water; ethyl acetate;	3-t-butoxycarbonylamino-1,2-propanediol (II) 3-amino-1,2-propanediol (10g, 0.11moles) was dissolved in water (250mL). The solution was cooled to 0C and Boc anhydride (25g. 0.12 moles) added in one portion. The reaction mixture was brought to room temperature and the pH maintained at 10.5 using NaOH (2M) until the pH remained constant. The reaction mixture was stirred for a further 16h. at room temperature then EtOAc (200mL) added and the pH adjusted to 2.5 using HCl (4M) at 0C. The phases were separated and the aqueous phase extracted with EtOAc (10x150mL). The combined organic phases were dried (MgSO4) then evaporated in vacuo to yield V as an oil. The product solidified upon freezing (20.4g, 97%). Rf=0.75(A), 0.60(B), FAB MS 192 (M+1)+, 1H n.m.r. (200MHz, CDCl3); 1.39(s,9H,Boc Me), 3.14(broad, 2H, CH2), 3.52(m,2H,CH2), 3.68(m,1H,CH), 4.75(s,2H,2xOH), 5.52(m,1H,NH). 13C n.m.r. (50MHz, CDCl3); 28.17(Me), 42.55(NCH2), 63.48(CH2), 71.08(CH), 79.76(quaternary C), 157.1(C=O).
	With triethylamine; In methanol; dichloromethane; at 20 - 25℃;	EXAMPLE 2-27: Production of (S)-4-amino-13-hydroxy-18,20-dimethyl-7-thia-3,5,11,15-tetraazatricyclo [15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-10,16-dione (Compound 31) [Show Image] Step 1: Preparation of ((S)-2,3-dihydroxypropyl)carbamic acid tert-butyl ester [Show Image] (R)-3-Aminopropane-1,2-diol (3.02 g, 33.09 mmol) was dissolved in a mixed solvent of dichloromethane (5 ml) and methanol (25 ml), and then triethylamine (553 mul, 3.97 mmol) was added thereto. A dichloromethane (11 ml) solution of di-t-butyl bicarbonate (9.12 ml, 39.71 mmol) was dropwise added to the mixture at room temperature. After the mixed solution was stirred at room temperature for five hours, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate =2:3) to yield ((S)-2,3-dihydroxypropyl)carbamic acid tert-butyl ester (5.00 g). Physicochemical properties of ((S)-2,3-dihydroxypropyl)carbamic acid tert-butyl ester: Molecular weight: 191.Chemical shift value delta in 1H-NMR (270 MHz, in chloroform-d): 1.45 (9H, s), 2.78 (1H, d), 2.84 (1H, t), 3.19-3.36 (2H, m), 3.52-3.67 (2H, m), 3.69-3.80 (1H, m), 4.93 (1H, brs).
	With triethylamine; In methanol; at 20℃;	To a stirred solution of 3-amino-1,2-propanediol (10.0 g, 0.1 1 mol) and triethylamine (23 mL, 0.17 mol) in MeOH (200 mL) at room temperature was added di-tert-butyl dicarbonate (26.4 g, 0.12 mol). The resulting solution was left to stir at room temperature overnight. The reaction mixture was concentrated under reduced pressure then co-evaporated with toluene to remove all the MeOH. The crude residue was taken up in CH2Cl2 and, after cooling to 0C, imidazole and tert-butyl-(chloro)dimethylsilane were sequentially added. The resulting mixture was left to stir at this temperature for 2h. The reaction mixture was partitioned between water (100 mL) and CH2Cl2 (70 mL) and the aqueous layer was extracted with further CH2Cl2 (2 x 70 mL). The combined organics were dried over Na2SO4 and concentrated in vacuo. The crude residue was purified over silica gel eluting with n-hexane followed by 10 % ethyl acetate in hexanes to afford tert-butyl 3-(tert-butyldimethylsilyloxy)-2-hydroxypropylcarbamate (32.6 g, 97.3%) as a colourless oil. 1H-NMR (300 MHz, CDCl3) 5ppm: 0.09 (6 H, s), 0.91 (9 H, s), 1.46 (9 H, s), 2.86 (1 H, br d, J 4.2 Hz), 3.13 (1 H, ddd, J 14.1 , 6.7, 5.3 Hz), 3.30 - 3.43 (1 H, m), 3.54 (1 H, dd, J 10.1 , 6.2 Hz), 3.66 (1 H, dd, J 10.1 , 4.5 Hz), 3.70 - 3.80 (1 H, m), 4.98 (1 H, br s).
	With triethylamine; In dichloromethane; at 0 - 20℃;	General procedure: Diethanolamine 3 (or threoninol 5, 3-amino-1,2-propanediol 6)(0.047 mol) was dissolved in CH2Cl2 and triethylamine (9.60 g,0.095 mol) was slowly added. The solution was cooled to 0 C,and (Boc)2O (12.45 g, 0.057 mol) was added dropwise. Then themixed solution was left for stirring at room temperature overnight.The solvent was removed under reduce pressure to afford crudeproduct, which was further purified by silica gel column chromatography(CH2Cl2/CH3OH = 10/1, v/v) to give compound 3a (or5a, 6a).
	With triethylamine; In methanol; at 20℃; for 6h;	A solution of 3-aminopropane-1,2-diol (20 g, 220 mmol), TEA (61.2 ml, 439 mmol) and BOC2O (61.2 ml, 263 mmol) in MeOH (200 ml) was stirred at ambient temperature for 6 hr. The reaction mixture was concentrated under vacuum to give crude product. The residue was purified by silica gel Isolute Flash Si; 20 g prepacked column chromatography, eluted with methanol/dichloromethane (with 0.1% TFA) = 1/10. The combined organic fractions were concentrated under reduced pressure to give the title compound. ?H NMR (CDC13, 400 MHZ):3.76-3.73 (m, 1H), 3.60-3.57 (m, 2H), 3.28-3.25 (m, 2H), 1.45 (s, 9H).
	at 20℃;	For boc protected 3-amino-1 ,2-propanediol, the 3-amino-1 ,2-propanediol can be reacted at RT with a small excess (e.g. 1 .02 - 1 .1 eq.) of di-t-butyl dicarbonate (a.k.a. Boc anhydride) in an aprotic solvent such as DCM or THF. No base is needed and in some cases the reaction can be driven to completion by heating overnight. The product of the reaction can then be evaporated and used without further purification.
	With triethylamine; In methanol; at 20℃; for 5h;	3-Aminopropane-1,2-diol (30 g, 0.33 mol, 1.0 eq) was dissolved in methanol (600 mL) and triethylamine (69 mL, 0.51 mol, 1.5 eq) and di-tert-butyl dicarbonate (79.2 g, 0.36 mol, 1.1 eq), reacted at room temperature for 5 hours. After 1H-NMR, the reaction was complete and the concentration was light.Yellow oily crude (63g crude),Used directly in the next step without purification.
	With triethylamine; In methanol; at 20℃;	Di-/er/-butyl dicarbonate (264 g, 1.21 mol) was added to a stirred solution of 3- aminopropane-l,2-diol (100 g, 1.10 mol) and triethylamine (111 g, 1.10 mol) in MeOH (2000 mL) and the reaction stirred at room temperature overnight. The mixture was concentrated under reduced pressure and residual solvent removed by azeotrope with toluene to yield the crude material /tvV-butyl (2,3-dihydroxypropyl)carbamate (210 g) as a white solid. 1H NMR (400 MHz, CDCl3) d 5.31 (s, 1H), 3.94-3.68 (m, 3H), 3.66-3.51 (m, 2H), 3.39-3.09 (m, 2H), 1.45 (s, 9H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 623 - 627
[2]Patent: US2016/151506,2016,A1 .Location in patent: Paragraph 0308-0312
[3]Canadian Journal of Chemistry,1997,vol. 75,p. 942 - 948
[4]Patent: US2006/69156,2006,A1 .Location in patent: Page/Page column 26
[5]Patent: US2006/154984,2006,A1 .Location in patent: Page/Page column 41
[6]Patent: US2006/35977,2006,A1 .Location in patent: Page/Page column 28
[7]Angewandte Chemie - International Edition,2015,vol. 54,p. 11696 - 11700
Angew. Chem.,2015,vol. 127,p. 11862 - 11866,5
[8]Patent: US2010/9950,2010,A1 .Location in patent: Page/Page column 23
[9]Patent: US9273058,2016,B2 .Location in patent: Page/Page column 449; 453
[10]MedChemComm,2017,vol. 8,p. 2050 - 2054
[11]Journal of Medicinal Chemistry,2014,vol. 57,p. 4969 - 4974
[12]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 4509 - 4512
[13]Journal of the American Chemical Society,2015,vol. 137,p. 12442 - 12445
[14]Journal of the American Chemical Society,2020,vol. 141,p. 2703 - 2712
[15]Synthesis,1998,p. 1113 - 1118
[16]Journal of Heterocyclic Chemistry,2008,vol. 45,p. 445 - 451
[17]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345
[18]Chemical and Pharmaceutical Bulletin,1991,vol. 39,p. 1972 - 1982
[19]Journal of Medicinal Chemistry,2006,vol. 49,p. 1191 - 1197
[20]Chemistry - A European Journal,2000,vol. 6,p. 4211 - 4217
[21]Patent: EP720615,2000,B1
[22]Patent: EP2119718,2009,A1 .Location in patent: Page/Page column 84-85
[23]RSC Advances,2013,vol. 3,p. 6771 - 6774
[24]Patent: WO2013/163675,2013,A1 .Location in patent: Paragraph 00181
[25]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 5756 - 5763
[26]Patent: WO2016/206101,2016,A1 .Location in patent: Page/Page column 193
[27]Patent: WO2018/175927,2018,A2 .Location in patent: Paragraph 00299
[28]Patent: CN109810041,2019,A .Location in patent: Paragraph 0203; 0207-0210
[29]Patent: WO2019/241751,2019,A1 .Location in patent: Paragraph 00367

2
[ 137618-48-5 ]
[ 620-05-3 ]
[ 137618-69-0 ]
[ 137618-53-2 ]
1,2-di(benzyloxy)-3-((tert-butoxycarbonyl)amino)propane [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1991,vol. 39,p. 1972 - 1982

3
[ 137618-48-5 ]
[ 18162-48-6 ]
[ 195197-94-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; triethylamine; In dichloromethane;	[3-(tert-Butyl-dimethyl-silanyloxy)-2-hydroxy-propyl]-carbamic Acid Tert-Butyl Ester To a solution of t-butyl N-(2,3-dihydroxypropyl)carbamate (9.0 g, 47 mmol) in CH2Cl2 (75 mL) was added t-butyldimethylsilyl chloride (7.80 g, 51.7 mmol), triethylamine (7.86 mL, 56.4 mmol) and DMAP (230 mg). The solution was stirred at rt overnight. After diluting with CH2Cl2 (50 mL), the solution was washed with water (2*100 mL), dried over MgSO4 and concentrated. The residual oil was distilled by Kugelrohr under vacuum to give the desired product (13.6 g, 95%). MS (DCI) m/z 306 (M+1)+.
76%	With dmap; triethylamine; In dichloromethane; at 20℃; for 16h;	Intermediate A1B: tert-Butyl (3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl) carbamate The above Intermediate was synthesized according to a patent literature procedure reported in U.S. Publication No. 2003/187026 A1 (2003). To a solution of Intermediate A1A (20.14 g, 105 mmol) in DCM (168 mL) were added TEA (17.62 mL, 126 mmol), TBSCl (18.00 g, 116 mmol) and DMAP (0.515 g, 4.21 mmol) and the reaction mixture was stirred at room temperature for 16 h. The mixture was then diluted with DCM (100 mL) and the organic layer was washed with water (3*100 mL), brine, dried over anhydrous MgSO4, filtered and the filtrate was concentrated under reduced pressure to provide a crude residue. It was purified by silica gel chromatography (330 g REDISEP column, eluting with a gradient of 0 to 30% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate A1B (24.46 g, 76%) as a pale yellow oil. 1H NMR (400 MHz, DMSO-d6) delta ppm 6.58 (br. s., 1H), 4.69 (d, J=4.4 Hz, 1H), 3.55-3.42 (m, 3H), 1.37 (s, 9H), 0.92-0.82 (m, 9H).
32.6 g	With 1H-imidazole; In dichloromethane; at 0℃; for 2h;	To a stirred solution of 3-amino-1,2-propanediol (10.0 g, 0.1 1 mol) and triethylamine (23 mL, 0.17 mol) in MeOH (200 mL) at room temperature was added di-tert-butyl dicarbonate (26.4 g, 0.12 mol). The resulting solution was left to stir at room temperature overnight. The reaction mixture was concentrated under reduced pressure then co-evaporated with toluene to remove all the MeOH. The crude residue was taken up in CH2Cl2 and, after cooling to 0C, imidazole and tert-butyl-(chloro)dimethylsilane were sequentially added. The resulting mixture was left to stir at this temperature for 2h. The reaction mixture was partitioned between water (100 mL) and CH2Cl2 (70 mL) and the aqueous layer was extracted with further CH2Cl2 (2 x 70 mL). The combined organics were dried over Na2SO4 and concentrated in vacuo. The crude residue was purified over silica gel eluting with n-hexane followed by 10 % ethyl acetate in hexanes to afford tert-butyl 3-(tert-butyldimethylsilyloxy)-2-hydroxypropylcarbamate (32.6 g, 97.3%) as a colourless oil. 1H-NMR (300 MHz, CDCl3) 5ppm: 0.09 (6 H, s), 0.91 (9 H, s), 1.46 (9 H, s), 2.86 (1 H, br d, J 4.2 Hz), 3.13 (1 H, ddd, J 14.1 , 6.7, 5.3 Hz), 3.30 - 3.43 (1 H, m), 3.54 (1 H, dd, J 10.1 , 6.2 Hz), 3.66 (1 H, dd, J 10.1 , 4.5 Hz), 3.70 - 3.80 (1 H, m), 4.98 (1 H, br s).

15 g	With 1H-imidazole; In N,N-dimethyl-formamide; at 10 - 35℃;	To a solution of <strong>[137618-48-5]tert-butyl (2,3-dihydroxypropyl)carbamate</strong> (10 g) and imidazole (5.34 g) in N,N-dimethylformamide (150 mL) was added tert-butyldimethylchlorosilane (9.46 g), and the mixture was stirred overnight at room temperature. The reaction mixture was poured into water, and extracted with diethyl ether. The obtained organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (15 g). MS: [M+H-Boc]+ 206.2.
78 g	With 1H-imidazole; In dichloromethane; at 0℃; for 2h;	tert-Butyl (2,3-dihydroxypropyl)carbamate (63 g of crude) was dissolved in dichloromethane (600 mL), cooled to 0 C, and then imidazole (33.6 g, 0.50 mol, 1.5 eq) and TBSCl were added sequentially. (47.2g, 0.315, 0.95eq),The reaction was kept at 0 C for 2 hours. The reaction was completed by 1H-NMR. Water (500 mL) and dichloromethane (500 mL) were added and the mixture was separated.Sodium is dried, concentrated,The crude product was purified by silica gel column chromatography (100-200 mesh silica gel, petroleum ether / ethyl acetate = 0-10%).A colorless oil (78 g, yield: 78%).
	With 1H-imidazole; In dichloromethane; at 0 - 20℃;	A solution of /er/-butyl (2,3-dihydroxypropyl)carbamate (210 g, 1.10 mol) and imidazole (82.2 g, 1.21 mol) in DCM (1500 mL) was cooled to 0C. /er/-Butyldimethylsilyl chloride (166 g, 1.10 mol) was added to the reaction at 0 C, the mixture slowly warmed to room temperature and stirred overnight. The mixture was poured into water (1000 ml) and extracted with DCM (1000 mL). The combined organics were washed with water (2x 1000 ml), brine (1000 ml), dried (Na2S04) and concentrated under reduced pressure to yield the crude material tert- butyl (3 -{{tert- butyldimethylsilyl)oxy)-2-hydroxypropyl)carbamate (340 g) as a yellow oil. 1H NMR (400 MHz, CDCI3) d 5.08 (br s, 1H), 3.75-3.65 (m, 1H), 3.63-3.56 (m, 1H), 3.55-3.46 (m, 1H), 3.36-3.26 (m, 1H), 3.12-3.05 (m, 1H), 3.03-2.98 (m, 1H), 1.41 (s, 9H), 0.86 (s, 9H), 0.04 (s, 6H).

Reference： [1]Canadian Journal of Chemistry,1997,vol. 75,p. 942 - 948
[2]Patent: US2003/187026,2003,A1
[3]Patent: WO2020/6177,2020,A1 .Location in patent: Paragraph 0185; 0187
[4]Patent: US9273058,2016,B2 .Location in patent: Page/Page column 449; 453; 454
[5]Journal of Organic Chemistry,2007,vol. 72,p. 10009 - 10021
[6]Journal of Medicinal Chemistry,2006,vol. 49,p. 1191 - 1197
[7]Patent: WO2013/163675,2013,A1 .Location in patent: Paragraph 00181
[8]Patent: US2018/155333,2018,A1 .Location in patent: Paragraph 2142; 2143
[9]Patent: CN109810041,2019,A .Location in patent: Paragraph 0203; 0211-0214
[10]Patent: WO2019/241751,2019,A1 .Location in patent: Paragraph 00368

4
[ 137618-48-5 ]
[ 124-63-0 ]
[ 213475-72-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 623 - 627
[2]Synthesis,1998,p. 1113 - 1118
[3]Chemical and Pharmaceutical Bulletin,2010,vol. 58,p. 405 - 407

5
[ 137618-48-5 ]
[ 878806-92-9 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1191 - 1197

6
[ 137618-48-5 ]
[ 878806-93-0 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1191 - 1197

7
[ 137618-48-5 ]
[ 878806-94-1 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1191 - 1197

8
[ 137618-48-5 ]
[ 849833-82-5 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

9
[ 137618-48-5 ]
N-(2-Boc-aminoethyl)-N-(thymin-1-ylacetyl)-D-leucine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

10
[ 137618-48-5 ]
[ 849833-84-7 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

11
[ 137618-48-5 ]
(R)-2-[2-tert-Butoxycarbonylamino-eth-(E)-ylideneamino]-4-methyl-pentanoic acid benzyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

12
[ 137618-48-5 ]
(S)-2-[2-tert-Butoxycarbonylamino-eth-(E)-ylideneamino]-4-methyl-pentanoic acid benzyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

13
[ 137618-48-5 ]
[ 849833-81-4 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

14
[ 137618-48-5 ]
N-(Boc-aminoethyl)-N-(thymin-1-ylacetyl)-L-leucine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

15
[ 137618-48-5 ]
[ 849833-83-6 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 3339 - 3345

16
[ 137618-48-5 ]
1,2-diamino-3-(BOC-amino)propane [ No CAS ]

Reference： [1]Synthesis,1998,p. 1113 - 1118

17
[ 137618-48-5 ]
[ 190840-29-0 ]

Reference： [1]Synthesis,1998,p. 1113 - 1118

19
[ 13154-24-0 ]
[ 137618-48-5 ]
3-(t-butoxycarbonylamino)-2-hydroxypropyl triisopropylsilyl ether [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With 1H-imidazole; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 3h;	To a 0 C mixture of 3-(t-butoxycarbonylamino)-2-hydroxypropanol (22.5 g, 118 mmol), imidazole (8.8 g, 130mmol) and DMF (450 ml) was added triisopropylsilyl chloride(25 mL, 118 mmol). The reaction was warmed to roomtemperature and stirred for 3 h. The reaction wasconcentrated to a slurry, CH2C12 was added, and the mixturefiltered.' The filtrate was washed with water (2X) andconcentrated. The reaction was repeated. The combinedcrude product was chromatographed with SiC>2 (hexanes to 30%EtOAc/hexanes) to give the title compound (62.2 g, 76%).iNMR (300 MHz, DMSO-dg): 8 1.03 (m, 21H) , 1.34 (s, 9H) , 2.87(m, 1H) , 3.08 (m, 1H) , 3.50 (m, 2H) , 4.67 (m, 1H) , 6,56 (m,1H) . ,ES-MS, exact m/e: calc. 370.2390 (CivHsvNC^Si) ;found 370.2372.

Reference： [1]Patent: WO2004/108677,2004,A1 .Location in patent: Page 161-162

20
[ 137618-48-5 ]
1-tert-butyloxycarbonylamino-3-iodopropane-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%		1-[(tert-butyloxycarbonyl)amino]propane-2,3-diol (example 17a) (3.88 g, 20 mmol) was dissolved in toluene (250 ml). Imidazole (1.73 g, 25 mmol), triphenylphosphine (6.65 g, 25 mmol) and iodine (5.15 g, 20 mmol) were then added in that order. The reaction medium was stirred at room temperature for 17 hours and 0.5 equivalents of imidazole, triphenylphosphine and iodine were added. After 21 hours of reaction, a saturated sodium sulfite solution was added until complete blanching of the reaction medium. The phases were allowed to settle and the aqueous phase was extracted twice with toluene. The combined organic phases were washed with saturated sodium chloride solution, dried on magnesium sulfate, filtered and the solvent evaporated. The residue obtained (11.02 g) was purified by chromatography on silica gel (eluent: dichloromethane/ethyl acetate 95:5) to give the desired compound as a yellow paste which was promptly used in the next reaction. Yield: 41% Rf (dichloromethane/methanol 98:2): 0.24 IR: nuNH amide 3387 cm-1; nuCO carbamate 1678 cm-1
41%	With 1H-imidazole; iodine; triphenylphosphine; In toluene; at 20℃; for 21h;	Example 27; Preparation of 1-amino-2-tetradecylthioacetyloxy-3-tetradecylthioacetylthiopropane hydrochloride; Preparation of 1-tert-butyloxycarbonylamino-3-iodopropan-2-ol (example 27a); 1-[(tert-butyloxycarbonyl)amino]propane-2,3-diol (example 22a) (3.88 g, 20 mmol) was dissolved in toluene (250 ml). Imidazole (1.73 g, 25 mmol), triphenylphosphine (6.65 g, 25 mmol) and iodine (5.15 g, 20 mmol) were then added in that order. The reaction medium was stirred at room temperature for 17 hours and 0.5 equivalents of imidazole, triphenylphosphine and iodine were added. After 21 hours of reaction, a saturated sodium sulfite solution was added until complete blanching of the reaction medium. The phases were allowed to settle and the aqueous phase was extracted twice with toluene. The combined organic phases were washed with saturated sodium chloride solution, dried on magnesium sulfate, filtered and the solvent evaporated. The residue obtained (11.02 g) was purified by chromatography on silica gel (eluent dichloromethane/ethyl acetate 95:5) to give the desired compound as a yellow paste which was promptly used in the next reaction. Yield: 41% Rf (dichloromethane/methanol 98:2): 0.24 IR: vNH amide 3387 cm-1; vCO carbamate 1678 cm-1
41%	With 1H-imidazole; iodine; triphenylphosphine; In toluene; at 20℃; for 38h;	Preparation of 1-tert-butyloxycarbonylamino-3-iodopropane-2-ol (example 22a) 1-[(tert-butyloxycarbonyl)amino]propane-2,3-diol (example 17a) (3.88 g, 20 mmol) was dissolved in toluene (250 ml). Imidazole (1.73 g, 25 mmol), triphenylphosphine (6.65 g, 25 mmol) and iodine (5.15 g, 20 mmol) were then added in that order. The reaction medium was stirred at room temperature for 17 hours and 0.5 equivalents of imidazole, triphenylphosphine and iodine were added. After 21 hours of reaction, a saturated sodium sulfite solution was added until complete blanching of the reaction medium. The phases were allowed to settle and the aqueous phase was extracted twice with toluene. The combined organic phases were washed with saturated sodium chloride solution, dried on magnesium sulfate, filtered and the solvent evaporated. The residue obtained (11.02 g) was purified by chromatography on silica gel (eluent:dichloromethane/ethyl acetate 95:5) to give the desired compound as a yellow paste which was promptly used in the next reaction. Yield: 41% Rf (dichloromethane/methanol 98:2): 0.24 IR: nuNH amide 3387 cm-1; nuCO carbamate 1678 cm-1

Reference： [1]Patent: US2006/69156,2006,A1 .Location in patent: Page/Page column 29
[2]Patent: US2006/154984,2006,A1 .Location in patent: Page/Page column 45
[3]Patent: US2006/35977,2006,A1 .Location in patent: Page/Page column 32

21
aqueous sodium chloride [ No CAS ]
[ 616-30-8 ]
[ 24424-99-5 ]
[ 137618-48-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; potassium hydrogen sulphate; In water; ethyl acetate;	EXAMPLE 14 3-(Boc-amino)-1,2-propanediol, 18 3-Amino-1,2-propanediol (40.00 g, 0.440 mol, 1.0 eqv) was dissolved in water (1000 ml) and cooled to 0 C., and di-tert-butyl dicarbonate (115.0 g, 0.526 mol, 1.2 eqv) was added in one portion. The reaction mixture was heated to room temperature on a water bath with stirring. The pH was maintained at 10.5 with a solution of sodium hydroxide (17.56 g, 0.440 mol, 1.0 eqv) in water (120 ml). When the addition of aqueous sodium hydroxide was completed, the reaction mixture was stirred overnight at room temperature. Subsequently, ethyl acetate (750 ml) was added to the reaction mixture followed by cooling to 0 C. and the pH was adjusted to 2.5 with 4N sulfuric acid with vigorous stirring. The phases were separated. The water phase was washed with additional ethyl acetate (6350 ml). The volume of the organic phase was reduced to 900 ml by evaporation under reduced pressure and washed with a saturated aqueous solution of potassium hydrogen sulfate diluted to twice its volume (11000 ml) and with saturated aqueous sodium chloride (1*500 ml). The organic phase was dried (MgSO4) and evaporated under reduced pressure to yield 50.12 9 (60%) of the title compound. The product could be solidified by evaporation from methylene chloride and subsequent freezing. 1 H-NMR (CDCl3 /TMS): delta=1.43 (s, 9H, Me3 C), 3.25 (m, 2H, CH2), 3.57 (m, 2H, CH2), 3.73 (m, 1H, CH). 13 C-NMR (CDCl3 /TMS): delta=28.2 (Me3 C), 42.6 (CH2), 63.5, 71.1 (CH2 OH, CHOH), 79.5 (Me3 C), 157.0 (C=O).

Reference： [1]Patent: US5539082,1996,A

22
[ 7790-21-8 ]
3-Amino-1,2-propanediol(80.0 g; 0.88 mol) [ No CAS ]
[ 24424-99-5 ]
[ 137618-48-5 ]
[ 89711-08-0 ]

Yield	Reaction Conditions	Operation in experiment
102 g (93%)	With hydrogenchloride; sodium hydroxide; In water; ethyl acetate;	(a) Preparation of (bocamino) acetaldehyde 3-Amino-1,2-propanediol(80.0 g; 0.88 mol) was dissolved in water (1500 ml) and the solution was cooled to 4 C., whereafter Boc anhydride (230 g; 1.05 mol) was added at once. The solution was gently heated to room temperature with a water bath. The pH was kept at 10.5 by the dropwise addition of sodium hydroxide. Over the course of the reaction a total of 70.2 g NaOH, dissolved in 480 ml water, was added. After stirring overnight, ethyl acetate (1000 ml) was added and the mixture was cooled to 0 C. and the pH was adjusted to 2.5 by the addition of 4M hydrochloric acid. The ethyl acetate layer was removed and the acidic aqueous solution was extracted with more ethyl acetate (8500 ml). The combined ethyl acetate solution was reduced to a volume of 1500 ml using a rotary evaporator. The resulting solution was washed with half saturated potassium hydrogen sulphate (1500 ml) and then with saturated sodium chloride. It then was dried over magnesium sulphate and evaporated to dryness, in vacuo. Yield. 145.3 g (86%) 3-Bocamino-1,2-propanediol (144.7 g; 0.757 mol) was suspended in water (750 ml) and potassium periodate (191.5 g; 0.833 mol) was added. The mixture was stirred under nitrogen for 2.5 h and the precipitated potassium iodate was removed by filtration and washed once with water (100 ml). The aqueous phase was extracted with chloroform (6400 ml). The chloroform extracts were dried and evaporated to dryness, in vacuoo Yield 102 g (93%) of an oil. The (bocamino)acetaldehyde was purified by kugelrohr distillation at 84 C. and 0.3 mmHg in two portions. The yield 79 g (77%) of a colorless oil.
102 g (93%)	With hydrogenchloride; sodium hydroxide; In water; ethyl acetate;	(a) Preparation of (bocamino)acetaldehyde 3-Amino-1,2-propanediol(80.0 g; 0.88 mol) was dissolved in water (1500 ml) and the solution was cooled to 4 C., whereafter Boc anhydride (230 g; 1.05 mol) was added at once. The solution was gently heated to room temperature with a water bath. The pH was kept at 10.5 by the dropwise addition of sodium hydroxide. Over the course of the reaction a total of 70.2 g NaOH, dissolved in 480 ml water, was added. After stirring overnight, ethyl acetate (1000 ml) was added and the mixture was cooled to 0 C. and the pH was adjusted to 2.5 by the addition of 4 M hydrochloric acid. The ethyl acetate layer was removed and the acidic aqueous solution was extracted with more ethyl acetate (8500 ml). The combined ethyl acetate solution was reduced to a volume of 1500 ml using a rotary evaporator. The resulting solution was washed with half saturated potassium hydrogen sulphate (1500 ml) and then with saturated sodium chloride. It then was dried over magnesium sulphate and evaporated to dryness, in vacuo. Yield. 145.3 g (86%) 3-Bocamino-1,2-propanediol (144.7 g; 0.757 mol) was suspended in water (750 ml) and potassium periodate (191.5 g; 0.833 mol) was added. The mixture was stirred under nitrogen for 2.5 h and the precipitated potassium iodate was removed by filtration and washed once with water (100 ml). The aqueous phase was extracted with chloroform (6400 ml). The chloroform extracts were dried and evaporated to dryness, in vacuo. Yield 102 g (93%) of an oil. The (bocamino)acetaldehyde was purified by kugelrohr distillation at 84 C. and 0.3 mmHg in two portions. The yield 79 g (77%) of a colorless oil.

Reference： [1]Patent: US5539082,1996,A
[2]Patent: US6228982,2001,B1

23
[ 7790-21-8 ]
[ 616-30-8 ]
[ 24424-99-5 ]
[ 137618-48-5 ]
[ 89711-08-0 ]

Yield	Reaction Conditions	Operation in experiment
102 g (93%)	With hydrogenchloride; sodium hydroxide; In water; ethyl acetate;	(a) Preparation of (bocamino)acetaldehyde 3-Amino-1,2-propanediol (80.0 g; 0.88 mol) was dissolved in water (1500 ml) and the solution was cooled to 4 C., whereafter Boc anhydride (230 g; 1.05 mol) was added at once. The solution was gently heated to room temperature with a water bath. The pH was kept at 10.5 by the dropwise addition of sodium hydroxide. Over the course of the reaction a total of 70.2 g NaOH, dissolved in 480 ml water, was added. After stirring overnight, ethyl acetate (1000 ml) was added and the mixture was cooled to 0 C. and the pH was adjusted to 2.5 by the addition of 4 M hydrochloric acid. The ethyl acetate layer was removed and the acidic aqueous solution was extracted with more ethyl acetate (8500 ml). The combined ethyl acetate solution was reduced to a volume of 1500 ml using a rotary evaporator. The resulting solution was washed with half saturated potassium hydrogen sulphate (1500 ml) and then with saturated sodium chloride. It then was dried over magnesium sulphate and evaporated to dryness, in vacuo. Yield. 145.3 g (86%) 3-Bocamino-1,2-propanediol (144.7 g; 0.757 mol) was suspended in water (750 ml) and potassium periodate (191.5 g; 0.833 mol) was added. The mixture was stirred under nitrogen for 2.5 h and the precipitated potassium iodate was removed by filtration and washed once with water (100 ml). The aqueous phase was extracted with chloroform (6400 ml). The chloroform extracts were dried and evaporated to dryness, in vacuo. Yield 102 g (93%) of an oil. The (bocamino)acetaldehyde was purified by kugelrohr distillation at 84 C. and 0.3 mmHg in two portions. The yield 79 g (77%) of a colorless oil.

Reference： [1]Patent: US6713602,2004,B1

24
[ 137618-48-5 ]
[ 148982-76-7 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; methanesulfonyl chloride; at 0℃;	Step 2: (R)-1-oxiranylmethylcarbamic acid tert-butyl ester [Show Image] ((S)-2,3-Dihydroxypropyl)carbamic acid tert-butyl ester (5.00 g, 26.16 mmol) obtained in Step 1 above was dissolved in pyridine (32 ml), and cooled to 0C. Methanesulfonyl chloride (2.22 ml, 28.71 mmol) was dropwise added to the solution, and stirred for 10 minutes. This solution was dropwise added to a solution of sodium hydroxide (3.18 g, 79.61 mmol) in water (33 ml) and dimethylsulfoxide (22 ml) at 0C, and stirred for 10 minutes. This reaction solution was poured into ice water (300 ml), and then extracted with a mixture of n-hexane (80 ml) and ethyl acetate (320 ml). The organic layer was separated and washed with water and a saturated aqueous sodium chloride solution, and then dried over anhydrous sodium sulfate. After the inorganic salt was removed by filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: n-hexane to n-hexane:ethyl acetate =4:1) to yield (R)-1-oxiranylmethylcarbamic acid tert-butyl ester (2.26 g). Physicochemical properties of (R)-1-oxiranylmethylcarbamic acid tert-butyl ester: Molecular weight: 173.Chemical shift value delta in 1H-NMR (270 MHz, in chloroform-d): 2.60 (1H, dd, J=4.7 Hz, 2.6 Hz), 2.78 (1H, dd, J=4.7 Hz, 4.0 Hz), 3.06-3.12 (1H, m), 3.15-3.27 (1H, m), 3.45-6.60 (1H, m), 4.73 (1H, brs).

Reference： [1]Patent: EP2119718,2009,A1 .Location in patent: Page/Page column 85

25
[ 137618-48-5 ]
[ 124-63-0 ]
[ 1184302-69-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine; In dichloromethane; at 20℃; for 2h;	Preparation F: (2RS)-2-aminomethyl-2,3-dihydro-1-oxa-3a,7-diaza-phenalen-4-oneF.i. Methanesulfonic acid 3-tert-butoxycarbonylamino-2-hydroxy-propyl esterA solution of rac-(2,3-dihydroxy-propyl)-carbamic acid tent-butyl ester (commercial; 1.9 g, 10 mmol) in DCM (100 mL) was treated sequentially with TEA (1.5 mL, 11 mmol) and dropwise with MsCl (0.78 mL, 10 mmol). A slightly exothermic reaction occurred and the mixture was stirred at rt for 2 h. The mixture was diluted with DCM, washed with water, dried over MgSO4 and concentrated to give a colourless oil (2.54 g, 94% yield) which was used as such in the next step without further purification.

Reference： [1]Patent: US2010/331318,2010,A1 .Location in patent: Page/Page column 30

26
[ 949086-94-6 ]
[ 137618-48-5 ]

Reference： [1]Synlett,2011,p. 821 - 825

27
[ 112-80-1 ]
[ 137618-48-5 ]
C₄₄H₈₁NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33.3%		General procedure: To the solution of oleic acid (3.75 g, 13.2 mmol) and 4-dimethylaminopyridine(DMAP) (270 mg) in CH2Cl2 at 0 C,N,N0-Dicyclohexylcarbodiimide (DCC) (2.75 g, 13.3 mmol) inCH2Cl2 were added dropwise. After 30 min, compound 3a (or 5a,or 6a) (11 mmol) was added, then the mixture was left for stirringat room temperature overnight. The reacting solution was cooledto 0 C, and the formed precipitate was filtered off. The filtratewas evaporated to give the residue, which was purified by silicagel column chromatography (PE/EA = 3/1, v/v) to give compound3b (or 5b, 6b).
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 24h;Inert atmosphere;	Oleic acid (10mmol) was dissolved in 20ml of 12 dichloromethane, then 13 N-Boc-3-amino-glycerine (3.3mmol), 14 EDC (3mmol) and 15 DMAP (3mmol) were added. The reaction mixture was stirred at room temperature for 24h under nitrogen. After reaction, the obtained 16 Boc protected 1,2-dioleoyl-3-amino-propane (DOAP) was isolated and purified by silica column chromatography (petroleum ether/ethyl acetate 20:1).

Reference： [1]Chemistry and Physics of Lipids,2012,vol. 165,p. 809 - 817
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 5756 - 5763
[3]Journal of Controlled Release,2018,vol. 279,p. 53 - 68
[4]Patent: US10426745,2019,B2 .Location in patent: Page/Page column 35; 36

28
C₉H₁₄O₂ [ No CAS ]
[ 137618-48-5 ]
C₁₅H₂₁NO₄ [ No CAS ]

Reference： [1]RSC Advances,2013,vol. 3,p. 6771 - 6774

29
[ 137618-48-5 ]
[ 1449513-71-6 ]

Reference： [1]RSC Advances,2013,vol. 3,p. 6771 - 6774

30
[ 137618-48-5 ]
[ 1251455-27-2 ]

Reference： [1]Journal of the American Chemical Society,2013,vol. 135,p. 7593 - 7602

31
[ 137618-48-5 ]
tert-butyl (2-(((tert-butyldimethylsilyl)oxy)methyl)-3-fluoroallyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1
[2]Patent: CN109810041,2019,A
[3]Patent: WO2020/6177,2020,A1

32
[ 137618-48-5 ]
tert-butyl (E)-(3-fluoro-2-(hydroxymethyl)allyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1
[2]Patent: WO2020/6177,2020,A1

33
[ 137618-48-5 ]
tert-butyl (Z)-(3-fluoro-2-(hydroxymethyl)allyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1

34
[ 137618-48-5 ]
(Z)-(2-(bromomethyl)-3-fluoroallyl)carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1

35
[ 137618-48-5 ]
(E)-(2-(bromomethyl)-3-fluoroallyl)carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1
[2]Patent: CN109810041,2019,A
[3]Patent: WO2020/6177,2020,A1

36
[ 137618-48-5 ]
(Z)-tert-butyl 2-((4-(dimethylcarbamoyl)phenoxy)-methyl)-3-fluoroallylcarbamate [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1

37
[ 137618-48-5 ]
(Z)-tert-butyl 2-((4-(N,N-dimethylsulfamoyl)phenoxy)methyl)-3-fluoroallylcarbamate [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1

38
[ 137618-48-5 ]
C₁₀H₁₈FNO₅S [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1

39
[ 137618-48-5 ]
C₁₀H₁₈FNO₅S [ No CAS ]

Reference： [1]Patent: WO2013/163675,2013,A1

40
[ 137618-48-5 ]
[ 106-96-7 ]
tert-butyl 2,3-bis(prop-2-ynyloxy)propylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 16h;	Preparation of Intermediate tert-butyl 2, 3-bis(prop-2-ynyloxy)prop ylcarbamate (I-i 3a):To <strong>[137618-48-5]tert-butyl 2,3-dihydroxypropylcarbamate</strong> (1.912 g, 10 mmol) in DMF (33.3 mL) at 0C was added propargyl bromide (3.45 mL, 40.0 mmol), and then potassium hydroxide (2.244 g, 40.0 mmol) slowly. The mixture was stirred at room temperature for 16h. Water was added to the mixture, and then extracted twice with AcOEt, washed with brine, dried over MgSO4,filtered, and concentrated. The crude product was purified by silica gel chromatography (0-20%AcOEt/heptane), giving tert-butyl 2,3-bis(prop-2-ynyloxy)propylcarbamate (l-13a: 1.583 g, 59%)as a colorless oil. 1H NMR (400 MHz,CDCI3) 6 ppm 1.38- 1.53 (m, 9 H) 2.47 (s, 2 H) 3.12-3.33 (m, 1 H) 3.46 (m, 1 H) 3.58 - 3.74 (m, 2 H) 3.76 - 3.91 (m, 1 H) 4.21 (t, J=1 .77 Hz, 2 H)4.26 - 4.42 (m, 2 H) 4.93 (br. s., 1 H).

Reference： [1]Patent: WO2013/9564,2013,A1 .Location in patent: Page/Page column 82; 83
[2]Chemical Science,2014,vol. 5,p. 4302 - 4311

41
[ 137618-48-5 ]
[ 139200-37-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 4969 - 4974
[2]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 4509 - 4512

42
[ 124-07-2 ]
[ 1632462-16-8 ]
[ 137618-48-5 ]
[ 1632462-24-8 ]

Reference： [1]Journal of the American Oil Chemists' Society,2014,vol. 91,p. 1225 - 1233

43
[ 137618-48-5 ]
C₁₀H₁₇NO₄*C₂HF₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 4509 - 4512

44
[ 137618-48-5 ]
C₉H₁₇NO₄S*C₂HF₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 4509 - 4512

45
[ 137618-48-5 ]
[ 139200-36-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 4509 - 4512

46
[ 137618-48-5 ]
[ 139200-36-5 ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 12442 - 12445
[2]Journal of the American Chemical Society,2020,vol. 141,p. 2703 - 2712

47
[ 108-24-7 ]
[ 137618-48-5 ]
2,3-di-O-acetyl-1-N-((tert-butoxycarbonyl)amino)propane [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2015,vol. 54,p. 11696 - 11700
Angew. Chem.,2015,vol. 127,p. 11862 - 11866,5
[2]MedChemComm,2017,vol. 8,p. 2050 - 2054

48
[ 137618-48-5 ]
ethyl 3-(3-fluorophenyl)-1-(2,2,3,3,11,11-hexamethyl-9-oxo-4,10-dioxa-8-aza-3-siladodecan-6-yl)-1H-pyrazole-5-carboxylate [ No CAS ]

Reference： [1]Patent: US9273058,2016,B2

49
[ 137618-48-5 ]
ethyl 3-(3-chlorophenyl)-1-(2,2,3,3,11,11-hexamethyl-9-oxo-4,10-dioxa-8-aza-3-siladodecan-6-yl)-1H-pyrazole-5-carboxylate [ No CAS ]

Reference： [1]Patent: US9273058,2016,B2

50
[ 137618-48-5 ]
diethyl 1-(2,2,3,3,11,11-hexamethyl-9-oxo-4,10-dioxa-8-aza-3-siladodecan-6-yl)-3-iodo-1H-pyrazole-4,5-dicarboxylate [ No CAS ]

Reference： [1]Patent: US9273058,2016,B2

51
[ 137618-48-5 ]
tosylated [ No CAS ]

Reference： [1]Patent: US2016/151506,2016,A1

52
[ 137618-48-5 ]
C₂₂H₂₉NO₆S [ No CAS ]

Reference： [1]Patent: US2016/151506,2016,A1

53
[ 137618-48-5 ]
C₁₅H₂₂ClNO₃ [ No CAS ]

Reference： [1]Patent: US2016/151506,2016,A1

54
[ 137618-48-5 ]
C₈H₁₆ClNO₃ [ No CAS ]

Reference： [1]Patent: US2016/151506,2016,A1

55
[ 137618-48-5 ]
C₂₄H₂₈ClNO₅ [ No CAS ]

Reference： [1]Patent: US2016/151506,2016,A1

56
[ 137618-48-5 ]
C₁₅H₂₂FNO₃ [ No CAS ]

Reference： [1]Patent: US2016/151506,2016,A1

57
[ 137618-48-5 ]
[ 648900-68-9 ]

Reference： [1]Patent: US2016/151506,2016,A1

58
[ 137618-48-5 ]
C₂₄H₂₈FNO₅ [ No CAS ]

Reference： [1]Patent: US2016/151506,2016,A1

59
[ 100-44-7 ]
[ 137618-48-5 ]
[ 137618-53-2 ]

Yield	Reaction Conditions	Operation in experiment
81%		1.91 g (1.0 eq., 9.96 mmol) of the compound 24 was dissolved in 20 mL of THF, and added with 251 mg (1.05 eq., 10.46 mmol) of sodium hydride followed by stirring for 15 minutes at room temperature. After that, under ice cooling, 1.24 mL (1.05 eq., 10.46 mmol) of benzyl chloride was added thereto and stirred overnight at room temperature. After confirming by TLC the disappearance of the reacting materials, the reaction solution was quenched with a saturated aqueous solution of NH4Cl under ice cooling and liquid fractionation extraction was performed 3 times by using ethyl acetate and water. The collected organic later was washed in order with a saturated aqueous solution of NH4Cl, a saturated aqueous solution of NaHCO3, and a saturated aqueous solution of NaCl. After drying over magnesium sulfate, it was concentrated under reduced pressure by using an evaporator in water bath at 40 C. The resulting reaction solution was purified by silica gel column chromatography (hexane:ethyl acetate=5:1) to obtain the desired compound 25 in an amount of 2.3 g (yield of 81%). 1H-NMR signal assignment is given in the following. 1H-NMR (500 MHz, CDCl3) delta1.44 (9H, s), 3.18 (1H, m), 3.29 (1H, m), 3.32 (1H, br), 3.45 (1H, dd), 3.54 (1H, dd), 3.63 (1H, m), 4.57 (2H, s), 4.91 (1H, br), 7.26-7.31 (5H, m).

Reference： [1]Patent: US2016/151506,2016,A1 .Location in patent: Paragraph 0308-0309; 0313-0315

60
[ 112-71-0 ]
[ 137618-48-5 ]
tert-butyl (2,3-bis(tetradecyloxy)propyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With tetra-(n-butyl)ammonium hydrogensulfate; sodium hydroxide; In water; toluene; at 60℃;	Tert-butyl-(2,3-dihydroxypropyl)carbamate (5) (1 g; 5.299 mmol) and 1-bromotetradecane (10.31 mL; 36.605 mmol) were dissolved in 10 mL of toluene. Subsequently, aqueous NaOH 50% (w/w) were added (10 mL) along with tetrabutylammonium hydrogensulphate (0.89 g; 2.615 mmol). The reaction mixture was heated at 60 C and vigorously stirred overnight. AcOEt (25 mL) was added to the reaction mixture and the organic phase was washed with (3x15 mL) of brine. The organic phase was dried with anhydrous MgSO4, filtrated and concentrated under reduced pressure. Crude was purified by flash chromatography TLC from hexane to 5% AcOEt (v/v) affording a colourless oily product (53% yield). Rf = 0.2 (Hexane:AcOEt 97:3); 1H-NMR (400 MHz, CDCl3) delta 4.88 (1H, broad s, Boc-NH-CH2CH(OC14H29)CH2(OC14H29)); 3.8-3.2 (9H, m, X-CHn where X= N,O ); 1.55 (4H, m, -CH(OCH2CH2CH2R)CH2(OCH2CH2CH2R) ); 1.44 (9H, s, (CH3)3C-O-CO-NH-R)); 1.26 (44H, s, aliphatic chains); 0.88 (6H, t, J = 6.8 Hz, R-CH2CH3) ppm. MS (ESI, low res. positive mode). Calcd. for [M+H]+ = 584.5619. Found: [M+H]+ = 584.5605. Calcd. for [M+Na]+ = 606.5432. Found: [M+Na]+ = 606.5425. Calcd for [2M+Na]+ = 1190.0971. Found: [2M+Na]+ = 1190.0966
44%	With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide; In water; toluene; at 65℃;Sealed tube;	In a 50 mL sealed cap glass vial, a mixture of <strong>[137618-48-5]tert-butyl (2,3-dihydroxypropyl)carbamate</strong> (1.15 g, 6.0 mmol) in toluene (6.0 mL) was treated sequentially with 1-bromotetradecane (10.71 mL, 36 mmol), sodium hydroxide (50% aq.; 6.0 mL) and tetrabutylammonium bisulfate (1.02 g, 3.0 mmol). The vial was sealed and heated at 65 C with vigorous stirring overnight. The mixture was cooled to room temperature (rt) and extracted with toluene (2 x 25 mL). The combined organic layers were washed with water, dried over sodium sulfate, and evaporated. The resulting colorless liquid was purified by silica gel column chromatography (hexane-ethyl acetate (0-25%)) to give the title compound as a colorless liquid (1.52 g, 44% yield). 1H NMR (500 MHz, Chloroform-d) delta 4.88 (s, 1H), 3.57 (dt, J = 9.3, 6.7 Hz, 1H), 3.52 - 3.29 (m, 7H), 3.17 (dt, J = 12.1, 5.7 Hz, 1H), 1.63 - 1.48 (m, 5H), 1.44 (s, 9H), 1.25 (s, 44H), 0.88 (t, J = 6.9 Hz, 6H); ESI-MS m z (0352) [M+H]+ calc'd for C36H73N04, 585; found, 585.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 175 - 186
[2]Patent: WO2018/26866,2018,A1 .Location in patent: Paragraph 0157

61
[ 137618-48-5 ]
[ 18162-48-6 ]
tert-butyl (2,3-bis((tert-butyldimethylsilyl)oxy)propyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-imidazole; In dichloromethane; at 20℃; for 16h;	A solution of <strong>[137618-48-5]tert-butyl (2,3-dihydroxypropyl)carbamate</strong> (10 g, 52.3 mmol), tertbutylchlorodimethylsilane (17.34 g, 115 mmol) and 1H-imidazole (14.24 g, 209 mmol) in Dichloromethane (200 ml) was stirred at ambient temperature for 16 hr. The reaction mixture was filtered and filtrate was concentrated under vacuum to give crude product. The residue was purified by silica gel Isolute Flash Si; 20 g prepacked column chromatography, eluting with ethyl acetate/petroleum ether(1/3). The combined organic fractions were concentrated under reducedpressure to give the title compound. ?H NMR (CDC13, 400 MHZ): 3.72-3.69 (m, 1H), 3.49-3.43 (m, 2H), 3.21-3.13 (m, 2H), 1.39 (s, 9H), 0.86-0.81 (m, 18H), 0.04-0.00 (m, 12H).

Reference： [1]Patent: WO2016/206101,2016,A1 .Location in patent: Page/Page column 193; 194

62
[ 137618-48-5 ]
tert-butyl (2-((tert-butyldimethylsilyl)oxy)-3-hydroxypropyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

63
[ 137618-48-5 ]
3-((tert-butoxycarbonyl)amino)-2-((tert-butyldimethylsilyl)oxy)propyl methanesulfonate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

64
[ 137618-48-5 ]
S-(3-((tert-butoxycarbonyl)amino)-2-((tert-butyldimethylsilyl)oxy)propyl) ethanethioate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

65
[ 137618-48-5 ]
tert-butyl (2-((tert-butyldimethylsilyl)oxy)-3-mercaptopropyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

66
[ 137618-48-5 ]
tert-butyl (3-((2-(N,N-bis(4-methoxybenzyl)sulfamoyl)-4-iodo-3-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)phenyl)thio)-2-((tert-butyldimethylsilyl)oxy)propyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

67
[ 137618-48-5 ]
tert-butyl 3-(2-(N,N-bis(4-methoxybenzyl)sulfamoyl)-4-iodo-3-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)phenylthio)-2-hydroxypropylcarbamate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

68
[ 137618-48-5 ]
tert-butyl 3-(2-(N,N-bis(4-methoxybenzyl)sulfamoyl)-4-iodo-3-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)phenylsulfonyl)-2-hydroxypropylcarbamate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

69
[ 137618-48-5 ]
tert-butyl 3-(4-(2-aminobenzo[d]thiazol-4-yl)-2-(N,N-bis(4-methoxybenzyl)sulfamoyl)-3-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)phenylsulfonyl)-2-hydroxypropylcarbamate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

70
[ 1024602-74-1 ]
[ 137618-48-5 ]
C₃₄H₆₅NO₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		3 - Boc - NH - 1, 2 - propylene glycol (2g) in adding toluene (75 ml), ice water bath is added NaH (60%, 0 . 92g), reaction at room temperature for 2 hours, the instillment contains MsO - EG4- COOtBu (9.2g) toluene solution (80 ml), 60 C reaction overnight, HPLC detection, evaporation to dryness with toluene, DCM and join the various wash once with water, steam dry DCM to obtain the crude product. Column purification (the mobile phase is 1 - 2% MeOH/DCM) to obtain the product 6.4g (yield 75%).

Reference： [1]Patent: CN106905120,2017,A .Location in patent: Paragraph 0129; 0130

71
[ 629-04-9 ]
[ 137618-48-5 ]
tert-butyl (2,3-bis(heptyloxy)propyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With tetra-(n-butyl)ammonium iodide; sodium hydroxide; In water; toluene; at 50 - 60℃; for 6h;	Aqueous NaOH (50 %, 15 mL) and Bu4NI (2.76 g, 7.5 mmol) were added at room temperature to a stirred solution of t- Butyl (2,3-dihydroxypropyl) carbamate (3 g, 15 mmol) and 1-Bromoheptane (7.5 ml, 45 mmol) in toluene (30 mL). After vigorous stirring for 6 h at 50-60C, the reaction mixture was allowed to obtain ambient temperature, ethyl acetate and water were added. The organic phase was washed with brine and dried (Na2S04). The residue was purified by column chromatography using 10-20% Ethyl acetate in Hexane to get the desired product (3.0 g, 52%). ESI-MS m/z [M+H]+ calc'd for C22H45N04, 388; found, 388.

Reference： [1]Patent: WO2018/26866,2018,A1 .Location in patent: Paragraph 0262

72
[ 22071-15-4 ]
[ 137618-48-5 ]
Boc-amino-1,2-propanediol-ketoprofen [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20 - 35℃; for 3h;Cooling with ice;	Boc-amino-1,2-propanediol (Boc-NHCH2CH(OH)CH2OH, manufactured by Aldrich Chem. Co.) (2.05 mmol) was dissolved in 6 dichloromethane (2 ml), and a dichloromethane solution (4 ml) of 125 ketoprofen (4.11 mmol) (manufactured by Tokyo Kasei Kogyo) and a dichloromethane solution (1 ml) of 54 DMAP (0.803 mmol) were added thereto in this order, followed by stirring. The reaction solution was ice-cooled, and a dichloromethane solution (5 ml) of 50 WSCI·HCl (4.94 mmol) was added thereto, followed by stirring overnight while gradually returning to room temperature. The reaction solution was ice-cooled, and a dichloromethane solution (1 ml) of WSCI·HCl (1.24 mmol) was added thereto, followed by stirring at room temperature for 1 hour and then at 35C for 2 hours. 14 Ethyl acetate was added thereto, followed by washing with 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution and saturated brine consecutively. Dehydration drying with sodium. sulfate was carried out, and then the solvent was evaporated under reduced pressure. The thus obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate = 2:1, 0.5% triethylamine) to give the titled 142 compound (1.175 g, yield 87%). The structure was identified by 1H-NMR (CDCl3). 1H-NMR (500 MHz, CDCl3) delta (ppm) = 1.36-1.40 (9H, m, Boc), 1.42-1.53 (6H, m, - OCOCH(CH3)-), 3.10-3.30 (2H, m, BocNHCH2-), 3.65-3.82 (2H, m, -OCOCH(CH3)-), 3.99-4.36 (2H, m, BocNHCH2(CHO-)CH2O-), 4.49-4.76 (1H, m, BocNH-), 5.04-5.09 (1H, m, BocNHCH2(CHO-)CH2O-), 7.38-7.80 (18H, m, Aromatic)

Reference： [1]Patent: EP3363463,2018,A2 .Location in patent: Paragraph 0161

73
[ 137618-48-5 ]
[ 1200-22-2 ]
C₁₉H₃₃NO₄S₄ [ No CAS ]