[ CAS No. 75937-12-1 ] {[proInfo.proName]}

Name: 75937-12-1|Boc-Ahx-ol|97%
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Quality Control of [ 75937-12-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 75937-12-1 ]

SDS Specification

Alternatived Products of [ 75937-12-1 ]

Product Details of [ 75937-12-1 ]

CAS No. :	75937-12-1	MDL No. :	MFCD01862954
Formula :	C₁₁H₂₃NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BDLPJHZUTLGFON-UHFFFAOYSA-N
M.W :	217.31	Pubchem ID :	4146612
Synonyms :		Chemical Name :	Boc-Ahx-ol

Calculated chemistry of [ 75937-12-1 ] Expand+

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.91
Num. rotatable bonds :	9
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	60.67
TPSA :	58.56 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.44 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.88
Log Po/w (XLOGP3) :	1.67
Log Po/w (WLOGP) :	2.06
Log Po/w (MLOGP) :	1.55
Log Po/w (SILICOS-IT) :	1.63
Consensus Log Po/w :	1.96

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.65
Solubility :	4.92 mg/ml ; 0.0226 mol/l
Class :	Very soluble
Log S (Ali) :	-2.51
Solubility :	0.666 mg/ml ; 0.00306 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.69
Solubility :	0.442 mg/ml ; 0.00203 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	2.2

Safety of [ 75937-12-1 ]

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

Application In Synthesis of [ 75937-12-1 ]

* 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 [ 75937-12-1 ]
Downstream synthetic route of [ 75937-12-1 ]

[ 75937-12-1 ] Synthesis Path-Upstream 1~4

1
[ 75937-12-1 ]
[ 6404-29-1 ]

Reference： [1] Journal of the Chemical Society. Perkin Transactions 1, 2002, # 8, p. 1024 - 1025
[2] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 6, p. 1253 - 1262

2
[ 75937-12-1 ]
[ 142356-33-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2 h; Inert atmosphere	To 6-aminohexan-1-ol (0.500 g, 2.82 mmol, 1 equiv.) dissolved ina 1:1 dioxane/water mixture (12 mL) was added K2CO3 (1.870 g, 13.56 mmol, 4 equiv.) and mixed at room temperature for 10 min. Ditert-butyl dicarbonate (0.7 mL, 3.39 mmol, 1.2 equiv.) was added tothe mixture and allowed to mix overnight. The reaction was dilutedwith EtOAc (12 mL) and the organic layer separated. The layer was washed with 10percent HCl (2 × 10mL), dried overMgSO4 and concentratedin vacuo. The reaction yield was 0.570 g (2.62mmol, 93percent) and the productwas taken onto the next step without further purification. Rf: 0.50,(silica gel, 60percent (EtOAc/Hex)); 1H NMR (400 MHz, CDCl3): δ 4.51 (br s,1H), 3.61 (t, J=6.5 Hz, 2H), 3.09 (t, J=6.7 Hz, 2H), 1.42 (s, 9H), 1.55–1.30 (m, 8H) ppm; 13C NMR (100 MHz, CDCl3): δ 156.1, 79.0, 62.7, 40.4,32.6, 30.1, 28.4, 26.4, 25.3 ppm. NMR spectra are consistent with thosepreviously reported [41].To 6-(tert-butoxycarbonylamino)hexan-1-ol (0.600 g, 2.76 mmol, 1equiv.) in dry dichloromethane (14 mL) was added CBr4 (0.920 g,2.76 mmol, 1 equiv.) and PPh3 (0.720 g, 2.76 mmol, 1 equiv.) at 0 °C.The resulting mixture was allowed to warm to room temperature over2 h. The reaction was concentrated in vacuo and purified by columnchromatography to yield 0.696 g of 9 (2.48 mmol, 90percent). Rf: 0.57, (silicagel, 20percent (EtOAc/Hex); 1H NMR (400 MHz, CDCl3): δ 4.48 (br s), 3.66(t, J = 6.8 Hz, 2H), 3.09 (t, J = 6.5 Hz, 2H), 1.88–1.82 (m, 2H), 1.47(s, 9H), 1.54–1.18 (m, 6H) ppm; 13C NMR (100 MHz, CDCl3): δ 156.1,62.9, 51.1, 32.8, 28.5, 26.4, 25.4 ppm). NMR spectra are consistentwith those previously reported [42].
78%	With carbon tetrabromide; triphenylphosphine In toluene at 20℃; for 3 h; Inert atmosphere	Step 2: Synthesis of tert-butyl (6-bromohexyl)carbamate (3’):1004001 To a stirred solution of compound 2 (1 g, 4.61 mmol) in toluene (30 mL) were added Ph3P (1.81 g, 6.91 mmol) and CBr4 (2.29 g, 6.91 mmol) at RT under inert atmosphere and stirred for 3 h. The mixture was diluted with water (50 mL) and extracted with EtOAc (3 x 60 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude. The crude was purified (silica gel; 20percent EtOAc/ hexanes) to afford compound 3 (1 g, 78percent) as colorless oil. 1H NMR (400 MHz, CDC13): (54.51 (br s, 1H), 3.40 (t, J= 6.8 Hz, 2H),3.13-3.08 (m, 2H), 1.89-1.82 (m, 2H), 1.52-1.42 (m, 13H), 1.37-1.31 (m, 2H).
69%	With bromine; triethylamine; triphenylphosphine In dichloromethane at 20℃; for 3 h; Inert atmosphere	6-(Boc-Amino)-Hexyl Bromide (3) TEA (2.25 mL, 16.1 mmol) was added via syringe to triphenylphosphine (4.308 g, 16.4 mmol) dissolved in 10 mL of dichloromethane at 0° C. Bromine (0.830 mL, 16.2 mmol), diluted in 10 mL of dichloromethane, was added to the reaction mixture. Stirring was continued at 0° C. for 30 minutes. Compound 1, in 10 mL of dichlormethane, was added via syringe and the reaction mixture was stirred at room temperature. Absence of starting material was confirmed by TLC after 3 hours. The crude material was purified by flash column chromatography over silica gel with hexanes:ethyl acetate (3:1) to afford a yellow oil (2.794, 69percent). ¹H NMR (500 MHz, CDCl3): δ 4.62 (bs, 1H), 3.41 (t, 2H, J=13.5), 3.12 (guar, 2H, J=6.6, 6.8), 1.86 (quin, 2H, J=7.0, 7.7) 1.55-1.29 (m, 15H) ¹³C NMR (126 MHz, CDCl3): δ 155.97, 79.03, 40.41, 33.81, 32.63, 29.91, 28.41, 27.80, 25.93.

Reference： [1] Helvetica Chimica Acta, 1993, vol. 76, # 2, p. 884 - 892
[2] Biochimica et Biophysica Acta - General Subjects, 2016, vol. 1860, # 3, p. 486 - 497
[3] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 5, p. 510 - 515
[4] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 18, p. 4033 - 4036
[5] Patent: WO2015/77503, 2015, A1, . Location in patent: Paragraph 00400
[6] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 11, p. 1156 - 1161
[7] Patent: US9125942, 2015, B2, . Location in patent: Page/Page column 8
[8] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 605 - 611
[9] Journal of Polymer Science, Part A: Polymer Chemistry, 2017, vol. 55, # 18, p. 2971 - 2976
[10] Journal of Medicinal Chemistry, 1994, vol. 37, # 16, p. 2537 - 2551
[11] Journal of the Chemical Society, Perkin Transactions 2, 2002, # 5, p. 923 - 927
[12] Nano Letters, 2010, vol. 10, # 2, p. 484 - 489

3
[ 75937-12-1 ]
[ 603-35-0 ]
[ 142356-33-0 ]

Reference： [1] Patent: US6878715, 2005, B1,

4
[ 4048-33-3 ]
[ 24424-99-5 ]
[ 75937-12-1 ]
[ 603-35-0 ]
[ 142356-33-0 ]

Reference： [1] Patent: US2002/28823, 2002, A1,
[2] Patent: US6774130, 2004, B2,

[ 75937-12-1 ] Synthesis Path-Downstream 1~23

1
[ 4048-33-3 ]
[ 24424-99-5 ]
[ 75937-12-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	In dichloromethane; at 0 - 20℃;	Molecule 3 was prepared according to the reported method.S2 2.34 g 6-Amino-1-hexanol (20 mmol) was dissolved in CH2Cl2 (20 mL) and cooled to 0 C in an ice bath. 4.80 g Boc2O (1.1 eq., 22 mmol) was added and the reaction mixture was stirred overnight at room temperature. Solvent was removed by rotary evaporation and crude product was extracted with EtOAc from 10 % aqueous citric acid, saturated NaHCO3, and brine. The organic phase was dried over Na2SO4 and concentrated by rotary evaporation to yield compound 3 quantitatively. 1H NMR (400 MHz, CDCl3) delta 4.55 (s, 1H), 3.63 (t, J = 6.5 Hz, 2H), 3.11 (q, J = 6.6 Hz, 2H), 1.68-1.20 (m, 18H).

Reference： [1]Synthesis,1990,p. 366 - 368
[2]European Journal of Medicinal Chemistry,2010,vol. 45,p. 2480 - 2488
[3]Journal of the American Chemical Society,2016,vol. 138,p. 10766 - 10769
[4]Angewandte Chemie - International Edition,2018,vol. 57,p. 11683 - 11687
Angew. Chem.,2018,vol. 130,p. 11857 - 11861,5
[5]Organic Letters,2019,vol. 21,p. 4433 - 4438
[6]Chem,2019,vol. 5,p. 3166 - 3183
[7]ChemMedChem,2020
[8]Journal of the American Chemical Society,2006,vol. 128,p. 9211 - 9218
[9]Journal of Organic Chemistry,2001,vol. 66,p. 4115 - 4121
[10]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7050 - 7053
[11]European Journal of Organic Chemistry,2012,p. 1223 - 1229
[12]Angewandte Chemie - International Edition,2012,vol. 51,p. 8110 - 8113
[13]Journal of Medicinal Chemistry,2013,vol. 56,p. 2487 - 2499
[14]European Journal of Medicinal Chemistry,2013,vol. 63,p. 387 - 400
[15]Tetrahedron Letters,2001,vol. 42,p. 2587 - 2591
[16]Tetrahedron Letters,2007,vol. 48,p. 8318 - 8322
[17]Patent: US2014/371434,2014,A1 .Location in patent: Paragraph 0026; 0030; 0053
[18]Patent: US9125942,2015,B2 .Location in patent: Page/Page column 8
[19]Patent: US2015/353489,2015,A1 .Location in patent: Paragraph 0102; 0164; 0165
[20]Journal of the Chemical Society. Perkin transactions I,1995,p. 2581 - 2588
[21]Patent: WO2009/86429,2009,A1 .Location in patent: Page/Page column 78
[22]Journal of Medicinal Chemistry,2014,vol. 57,p. 4924 - 4939
[23]Angewandte Chemie - International Edition,2016,vol. 55,p. 8571 - 8574
Angew. Chem.,2016,vol. 128,p. 8713 - 8716,4
[24]Chemistry - A European Journal,2009,vol. 15,p. 3230 - 3242
[25]Journal of labelled compounds and radiopharmaceuticals,1999,vol. 42,p. 23 - 28
[26]Patent: WO2009/86429,2009,A1 .Location in patent: Page/Page column 83-84
[27]Synthesis,2011,p. 2724 - 2732
[28]Biochimica et Biophysica Acta - General Subjects,2016,vol. 1860,p. 486 - 497
[29]Organic Letters,2008,vol. 10,p. 837 - 840
[30]Journal of Medicinal Chemistry,2015,vol. 58,p. 5287 - 5307
[31]Patent: US9243040,2016,B2 .Location in patent: Page/Page column 34
[32]Organic Letters,2002,vol. 4,p. 737 - 740
[33]Journal of the American Chemical Society,2008,vol. 130,p. 655 - 664
[34]Journal of Medicinal Chemistry,1999,vol. 42,p. 2969 - 2976
[35]Journal of Medicinal Chemistry,2011,vol. 54,p. 2165 - 2182
[36]European Journal of Organic Chemistry,2019,vol. 2019,p. 2899 - 2913
[37]Patent: WO2013/33515,2013,A1 .Location in patent: Paragraph 00185
[38]Organic and Biomolecular Chemistry,2014,vol. 12,p. 4964 - 4974
[39]European Journal of Medicinal Chemistry,2017,vol. 127,p. 828 - 839
[40]Patent: JP2017/160163,2017,A .Location in patent: Paragraph 0121
[41]Journal of Medicinal Chemistry,2014,vol. 57,p. 9673 - 9686
[42]Journal of Medicinal Chemistry,2009,vol. 52,p. 3146 - 3149
[43]Journal of Medicinal Chemistry,2018,vol. 61,p. 4860 - 4882
[44]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 573 - 580
[45]Patent: US2018/194742,2018,A1 .Location in patent: Paragraph 0031; 0130; 0131
[46]Patent: US2018/346417,2018,A1 .Location in patent: Paragraph 0064; 0065
[47]Journal of Polymer Science, Part A: Polymer Chemistry,2010,vol. 48,p. 2869 - 2877
[48]Patent: WO2015/77503,2015,A1 .Location in patent: Paragraph 00399
[49]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 1253 - 1262
[50]Organic Letters,2005,vol. 7,p. 111 - 114
[51]Macromolecules,2003,vol. 36,p. 9784 - 9796
[52]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4828 - 4832
[53]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7671 - 7680
[54]Journal of the Chemical Society. Perkin Transactions 2 (2001),2002,p. 923 - 927
[55]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4208 - 4212
[56]Patent: US2002/177594,2002,A1
[57]Patent: US5332726,1994,A
[58]Patent: US5599587,1997,A
[59]Patent: US4550163,1985,A
[60]Patent: US4808605,1989,A
[61]Patent: US2003/220341,2003,A1 .Location in patent: Page/Page column 51
[62]Nano Letters,2010,vol. 10,p. 484 - 489
[63]Biomacromolecules,2012,vol. 13,p. 1632 - 1641
[64]Patent: US2011/275622,2011,A1 .Location in patent: Paragraph 0314
[65]Patent: US2012/309797,2012,A1 .Location in patent: Paragraph 0116
[66]Patent: US2014/363454,2014,A1 .Location in patent: Paragraph 0290' 0347
[67]Journal of Medicinal Chemistry,2015,vol. 58,p. 6559 - 6573
[68]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 283 - 287
[69]Patent: WO2016/106377,2016,A1 .Location in patent: Page/Page column 40-41
[70]Tetrahedron,2017,vol. 73,p. 3866 - 3877
[71]Patent: US2018/230385,2018,A1 .Location in patent: Paragraph 0204
[72]Journal of the American Chemical Society,2020,vol. 142,p. 726 - 732

2
[ 75937-12-1 ]
[ 142356-33-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 2h;Inert atmosphere;	To 6-aminohexan-1-ol (0.500 g, 2.82 mmol, 1 equiv.) dissolved ina 1:1 dioxane/water mixture (12 mL) was added K2CO3 (1.870 g, 13.56 mmol, 4 equiv.) and mixed at room temperature for 10 min. Ditert-butyl dicarbonate (0.7 mL, 3.39 mmol, 1.2 equiv.) was added tothe mixture and allowed to mix overnight. The reaction was dilutedwith EtOAc (12 mL) and the organic layer separated. The layer was washed with 10% HCl (2 × 10mL), dried overMgSO4 and concentratedin vacuo. The reaction yield was 0.570 g (2.62mmol, 93%) and the productwas taken onto the next step without further purification. Rf: 0.50,(silica gel, 60% (EtOAc/Hex)); 1H NMR (400 MHz, CDCl3): delta 4.51 (br s,1H), 3.61 (t, J=6.5 Hz, 2H), 3.09 (t, J=6.7 Hz, 2H), 1.42 (s, 9H), 1.55-1.30 (m, 8H) ppm; 13C NMR (100 MHz, CDCl3): delta 156.1, 79.0, 62.7, 40.4,32.6, 30.1, 28.4, 26.4, 25.3 ppm. NMR spectra are consistent with thosepreviously reported [41].To 6-(tert-butoxycarbonylamino)hexan-1-ol (0.600 g, 2.76 mmol, 1equiv.) in dry dichloromethane (14 mL) was added CBr4 (0.920 g,2.76 mmol, 1 equiv.) and PPh3 (0.720 g, 2.76 mmol, 1 equiv.) at 0 C.The resulting mixture was allowed to warm to room temperature over2 h. The reaction was concentrated in vacuo and purified by columnchromatography to yield 0.696 g of 9 (2.48 mmol, 90%). Rf: 0.57, (silicagel, 20% (EtOAc/Hex); 1H NMR (400 MHz, CDCl3): delta 4.48 (br s), 3.66(t, J = 6.8 Hz, 2H), 3.09 (t, J = 6.5 Hz, 2H), 1.88-1.82 (m, 2H), 1.47(s, 9H), 1.54-1.18 (m, 6H) ppm; 13C NMR (100 MHz, CDCl3): delta 156.1,62.9, 51.1, 32.8, 28.5, 26.4, 25.4 ppm). NMR spectra are consistentwith those previously reported [42].
78%	With carbon tetrabromide; triphenylphosphine; In toluene; at 20℃; for 3h;Inert atmosphere;	Step 2: Synthesis of tert-butyl (6-bromohexyl)carbamate (3?):1004001 To a stirred solution of compound 2 (1 g, 4.61 mmol) in toluene (30 mL) were added Ph3P (1.81 g, 6.91 mmol) and CBr4 (2.29 g, 6.91 mmol) at RT under inert atmosphere and stirred for 3 h. The mixture was diluted with water (50 mL) and extracted with EtOAc (3 x 60 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude. The crude was purified (silica gel; 20% EtOAc/ hexanes) to afford compound 3 (1 g, 78%) as colorless oil. 1H NMR (400 MHz, CDC13): (54.51 (br s, 1H), 3.40 (t, J= 6.8 Hz, 2H),3.13-3.08 (m, 2H), 1.89-1.82 (m, 2H), 1.52-1.42 (m, 13H), 1.37-1.31 (m, 2H).
69%	With bromine; triethylamine; triphenylphosphine; In dichloromethane; at 20℃; for 3h;Inert atmosphere;	6-(Boc-Amino)-Hexyl Bromide (3) TEA (2.25 mL, 16.1 mmol) was added via syringe to triphenylphosphine (4.308 g, 16.4 mmol) dissolved in 10 mL of dichloromethane at 0 C. Bromine (0.830 mL, 16.2 mmol), diluted in 10 mL of dichloromethane, was added to the reaction mixture. Stirring was continued at 0 C. for 30 minutes. Compound 1, in 10 mL of dichlormethane, was added via syringe and the reaction mixture was stirred at room temperature. Absence of starting material was confirmed by TLC after 3 hours. The crude material was purified by flash column chromatography over silica gel with hexanes:ethyl acetate (3:1) to afford a yellow oil (2.794, 69%). 1H NMR (500 MHz, CDCl3): delta 4.62 (bs, 1H), 3.41 (t, 2H, J=13.5), 3.12 (guar, 2H, J=6.6, 6.8), 1.86 (quin, 2H, J=7.0, 7.7) 1.55-1.29 (m, 15H) 13C NMR (126 MHz, CDCl3): delta 155.97, 79.03, 40.41, 33.81, 32.63, 29.91, 28.41, 27.80, 25.93.

Reference： [1]Helvetica Chimica Acta,1993,vol. 76,p. 884 - 892
[2]Biochimica et Biophysica Acta - General Subjects,2016,vol. 1860,p. 486 - 497
[3]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 510 - 515
[4]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4033 - 4036
[5]Patent: WO2015/77503,2015,A1 .Location in patent: Paragraph 00400
[6]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 1156 - 1161
[7]Patent: US9125942,2015,B2 .Location in patent: Page/Page column 8
[8]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 605 - 611
[9]Journal of Polymer Science, Part A: Polymer Chemistry,2017,vol. 55,p. 2971 - 2976
[10]Journal of Medicinal Chemistry,1994,vol. 37,p. 2537 - 2551
[11]Journal of the Chemical Society. Perkin Transactions 2 (2001),2002,p. 923 - 927
[12]Nano Letters,2010,vol. 10,p. 484 - 489

3
[ 75937-12-1 ]
[ 124-63-0 ]
[ 75950-19-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine; In dichloromethane; at 20℃; for 1h;Cooling with ice;	2.0 g of compound 3 (9.2 mmol) and 1.86 g TEA (18.4 mmol) were dissolved in 50 mL dry DCM under ice bath. 1.48 g methanesulfonyl chloride (MsCl, 12.9 mmol) was added dropwise. The reaction was stirred under ice bath for 0.5 h and another 1 h at room temperature. Then, the reaction mixture was washed by saturated NaHCO3, 1M HCl, saturated NaHCO3 and brine respectively. The organic phase was dried over Na2SO4 and concentrated by rotary evaporation. (2.58 g, 95%). 1H NMR (400 MHz, CDCl3) (delta ppm): delta 4.55 (s, 1H), 4.22 (t, J = 6.5 Hz, 2H), 3.20-3.05 (m, 2H), 3.02 (s, 3H), 1.68-1.20 (m, 17H).
85%	With triethylamine; In diethyl ether; benzene; at 8 - 20℃; for 7h;	General procedure: MsCl (2.07 g, 18.1 mmol) in 7 mL ofdry C6H6 was added during 20 min under stirring to thecooled (8C) solution of 5NBocaminopentanol1(3.86 g, 19 mmol) and Et3N (2.53 g, 25 mmol) in40 mL of C6H6/Et2O (2 : 1). The mixture was stirredfor 1 h at 8C and 6 h at 20C. The precipitate was filtered, and filtrates were washed successively with 1 NaHCO3 (3 × 10 mL), H2O (10 mL), 10% citric acid(2 × 10 mL), H2O (5 mL), and 5 NaCl (15 mL) anddried over MgSO4/NaHCO3. The solvent was evaporated in vacuum, the residue was triturated with hexane, the precipitate was filtered and dried in air,recrystallized from an Et2Ohexane mixture. Compound (X) was obtained in a yield of 4.32 g (81%).
	With triethylamine; In dichloromethane; at 0 - 20℃;	6-((tert-Butoxycarbonyl)amino)hexyl methanesulfonate. To a solution of tert-butyl (6-hydroxyhexyl)carbamate (12.18 g, 56.05 mmol) and TEA (8.51 g, 84.08 mmol) in 100 ml of methylene chloride, methanesulfonyl chloride (9.63 g, 84.08 mmol) was slowly added at 0C. The mixture was stirred at room temperature overnight. The compound was purified by silica chromatography using heptane/ethyl acetate as eluent.

	With triethylamine; In dichloromethane; at 0 - 20℃; for 5.5h;	General procedure: To a solution of N-Boc protected alcohol (60 mmol) and TEA (60 mmol) in dry DCM (100 mL) kept in an ice bath (0 C) was slowly added methane sulfonyl chloride (60 mmol)) and reaction mixture was stirred for 30 min at 0 C. The ice bath was removed and reaction mixture was further allowed to stir at room temperature for 5 h (Completion of the reaction was monitored by TLC). Then water (50 mL) was added with stirring, the resulting solution was transferred to a reparatory funnel, organic layer was separated and aqueous layer was extracted with DCM (2 × 75 mL). The combined organic layers were washed with brine (50 mL) dried over anhydrous sodium sulfate and concentrated on rotary evaporator. See individual experiments for more details.
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 20℃; for 1.5h;	Methanesulfonic acid 6-tert-butoxycarbonylamino-hexyl ester To a stirring solution of (6-Hydroxy-hexyl)-carbamic acid tert-butyl ester (5000 mg; 23 mmol; 1.00 eq.) in THF (60 mL) and Ethyl-diisopropyl-amine (5.63 mL; 32.21 mmol; 1.40 eq.) was added drop wise Methanesulfonyl chloride (2.23 mL; 28.76 mmol; 1.25 eq.) at 0 C. The reaction was stirred for 30 min at 0 C., then raised to RT for 1 h. EA (100 mL) was added, the organic layer was washed with brine, dried, and concentrated to provide a yellow solid (quantitative yield), which was directly used for the next step reaction. LC-MS (M+1): 296.

Reference： [1]European Journal of Medicinal Chemistry,2010,vol. 45,p. 2480 - 2488
[2]ChemMedChem,2020
[3]Chem,2019,vol. 5,p. 3166 - 3183
[4]Organic Letters,2002,vol. 4,p. 737 - 740
[5]Journal of Medicinal Chemistry,2015,vol. 58,p. 5287 - 5307
[6]Russian Journal of Bioorganic Chemistry,2016,vol. 42,p. 415 - 422
[7]Synthesis,1990,p. 366 - 368
[8]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4828 - 4832
[9]Journal of the Chemical Society. Perkin Transactions 2 (2001),2002,p. 923 - 927
[10]Journal of Organic Chemistry,2001,vol. 66,p. 4115 - 4121
[11]Journal of Medicinal Chemistry,2013,vol. 56,p. 2487 - 2499
[12]Patent: WO2013/33515,2013,A1 .Location in patent: Paragraph 00186
[13]Journal of Medicinal Chemistry,2014,vol. 57,p. 4924 - 4939
[14]European Journal of Medicinal Chemistry,2016,vol. 119,p. 300 - 318
[15]Patent: WO2016/106377,2016,A1 .Location in patent: Page/Page column 40-41
[16]Patent: US2016/229856,2016,A1 .Location in patent: Paragraph 0277; 0278
[17]Journal of Medicinal Chemistry,2018,vol. 61,p. 4860 - 4882

4
[ 75937-12-1 ]
[ 98-59-9 ]
[ 86536-92-7 ]

Yield	Reaction Conditions	Operation in experiment
62%	With pyridine; at 20℃; for 1h;	Dissolve 4.56 g (21.0 mmol) tert-butyl 6-hydroxycarbamate in 25 mL anhydrous pyride. Then slowly add 4.00 g (21.0 mmol) P-toluenesulfonyl chloride into the solution in an ice bath and stir the mixture at room temperature for 1 hour. Next add 25 mL water and concentrated hydrochloric acid for adjusting the pH value of the mixture to less than 7. Use 100 mL dichloromethane to extract twice. Take the organic layer, wash with 2N hydrochloric acid aqueous solution. Take the organic layer, add with anhydrous sodium sulfate for dehydration, and remove the solvent by vacuum evaporation. Use liquid chromatography (SiO2, EA:CHC13=1:2) for isolation and purification to get the product 4.82 g (62%) tert-butyl 6-toluenesulfonylhexylcarbamate.
54%	With pyridine; In dichloromethane; at 20℃; for 3.5h;Cooling with ice;	Pyridine (1.66g, 21.1 mmol) was added to an ice-cooled solution of tert-butyl (4-hydroxybutyl)carbamate (1.31 g,6.91 mmol) in CH2Cl2 (6 ml), followed by tosyl chloride(2.59 g, 13.6 mmol). The mixture was stirred at room temperature for 3.5 h. Solvent was removed under reduced pressure and the mixture was quenched with 1 N HCl and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated in vacuo.The products were purified by column chromatography.
29%	In dichloromethane; for 48h;	Compound 8 (2.0 g, 1 equ.) was dissolved in CH2Cl2, paratoluensulfonylchloride (2.1 g, 1.1 equ.) in CH2Cl2 was added dropwise into the solution. Then trimethylamine was added and thereactionwas stirred for another 48 h. After that, poured the solutioninto water and washed with NaCl, dried by Na2SO4, the solvent wasremoved under reduced pressure. The mixturewas further purifiedusing silica gel column chromatography using 510% petroleumether to ethylacetate gradient solvent system to afford the desiredpure product with colorless oily matter 9 (1.02, 29%). m.p.66-68 C. 1H NMR (300 MHz, CDCl3) delta: 7.77 (d, J = 8.3 Hz, 2H), 7.34(d, J = 8.0 Hz, 2H), 4.00 (t, J = 6.5 Hz, 2H), 3.05 (brs, 2H), 2.44 (s, 3H),2.04 (s, 1H), 1.42 (s, 9H), 1.3411.22 (m, 6H).

		Compound 11 DETAILED DESCRIPTION OF INDIVIDUAL STEPS[0025] 6-r-bMfyloxycarbonyl-amino-l-hexanol (also known as (BOC-amino)- 1-hexanol), compound (1) above, 34.45 grams (hereinafter abbreviated as "g."), was dissolved in 300 ml chloroform and the solution cooled to about 5C in an ice bath while under an argon purge. Triethylamine, 44.2 g. was added and the solution stirred for about 15 minutes. p-Toluene sulfonyl chloride, compound 2, 36.28 g., was added to the solution and the reaction flask was removed from the ice bath and continually stirred for about 4 hours at room temperature. The solution was then concentrated to a clear, slightly yellow oil by rotary evaporation at 300C and was azeotroped with 2 sequential extractions with 100 ml chloroform to yield a semi- solid product. The crude product was taken up in 500 ml of a 1:1 mixture of ethyl acetate and hexane, which caused the precipitation of a triethylamine HCl salt, which was removed by filtration. The filter cake was rinsed with 3 sequential rinses of about 75 ml ethyl acetate, which was combined with the filtrate. The filtrate was concentrated to an oil by rotary evaporation at 300C, yielding about 75 g, and was diluted in 75 ml chloroform. This was purified by flash column chromatography (silica gel) employing a mobile phase solution of hexane: ethyl acetate (5:1 through 1:1). Isolated fractions were then combined and concentrated to yield a white, cloudy oil product, 6-(BOC- amino)hexyl-p-toluenesulfonate, 56.59 g., compound 3 above. The structure was verified with NMR and the mass spectrum (ESI+) peak of 394.2 m/z [M+Na]+ is consistent with the sodium salt adduct.
10.9 mg	With pyridine; In dichloromethane; at 20℃;Cooling with ice;	General procedure: The product as obtained above (0.05 mol) and 11.4 g (0.06 mol) of p-toluenesulfonyl chloride were added to 50 mL of dichloromethane (treated with molecular sieve) in an ice bath with stirring, and the solid was dissolved completely. 12.1 mL (0.15 mol) of pyridine was added dropwise to the above solution, which was then allowed to stir at room temperature overnight. The reaction was stopped, and 50 mL of water was added. The organic layer was isolated, and the water layer was extracted with 50 mL×2 of dichloromethane. The organic layers were combined, successively washed with 125 mL of 5.0% citric acid aqueous solution, 125 mL of water and 125 mL of saturated saline, dried over anh. MgSO4, filtered, concentrated and dried under vacuum to obtain 13.9 mg of a white solid. Yield 74.7%.
	With pyridine; for 0.5h;Cooling with ice;	Example 167-(fert-butoxycarbonylamino)-2-(R1-sulfonyl)-l-heptanol[0093] p-Toluenesulfonyl chloride (1 mmol) is added to a solution of 6-azido-l-hexanol (Example 1, 1 mmol) in pyridine (2 mL) cooled on ice. After 30 min, the mixture is allowed to warm to ambient temperature and treated with R^-SH (1 mmol) for an additional 1 hr. The mixture is diluted with ethyl acetate, washed sequentially with water, 1 N HC1, water, sat. aq. NaHCC"3, and brine, then dried over MgS04, filtered, and evaporated. The crude thioether is dissolved in ethyl acetate and treated excess peracetic acid to prepare the sulfone. After standard aqueous workup, the sulfone is purified by chromatography on silica gel. A mixture of the sulfone, ethyl formate, and 2 equivalents of sodium hydride in DMF is warmed to 50C to provide an intermediate aldehyde, which is treated with sodium borohydride in methanol to produce the product alcohol. Example 17
		To a solution of tert-butyl N-(6-hydroxyhexyl)carbamate (2.0 g, 9.2 mmol) in DCM (30 mL) was added Et3N (2.6 mL, 18.4 mmol) and catalytic amount of DMAP. The mixture was stirred for 20 minutes, then to the mixture 4-methylbenzenesulfonyl chloride (1.75 g, 9.2 mmol) was added portionwise at 0 C. The resulting mixture was allowed to warm to room temperature and stirred for 16 hours. The mixture was washed with 1 M hydrochloric acid, followed by saturated aqueous NaHCO3 solution. The organic layer was dried over anhydrous Na2SO4 and concentrated to give 6-(tert-butoxycarbonylamino) hexyl 4-methylbenzenesulfonate.
		Step 1: Preparation of 6-(fc'r^butoxyearbonylamino) hexyl 4-methylbenzenesiilfonate To a solution of / /v-butyl N- (6-hyd ro x y h e x y 1 ) ca rba ma t c (2.0 g, 9.2 mmol ) in DCM (30 rriL) was added Eh (2.6 ml., 18.4 mmol ) and catalytic amount of DM A P. The mixture was stirred for 20 minutes, then to the mixture 4- met h y 1 be nze n esu 1 fo n y I chloride ( 1 .75 g, 9.2 mmol ) was added portionwise at 0 C. The resulting mixture was allowed to warm to room temperature and stirred for 16 hours. The mixture was washed with 1 M hydrochloric acid, followed by saturated aqueous NaHC'O ; solution. The organic layer was dried over anhydrous Na^SCt and concentrated to give 6-(tert-butoxycarbonylamino) hexyl 4-methylbenzenesulfonate.
4 g	With dmap; In dichloromethane; at 20℃;	Step 1: Preparation of 6-(tert-butoxycarbonylamino)hexyl 4-methyl benzenesulfonate To a mixture of tert-butyl N-(6-hydroxyhexyl)carbamate (4.83 g, 22.26 mmol) and triethylamine (3.72 mL, 26.7 mmol) in DCM (200 mL) at rt was added p-toluenesulfonyl chloride (5.09 g, 26.7 mmol) and DMAP (0.27 g, 2.23 mmol). After being stirred overnight, the resulting mixture was concentrated in vacuo and the residue was purified by flash column to give 6-(tert-butoxycarbonylamino)hexyl 4-methylbenzenesulfonate (4.0 g).
8.3 g		A mixture of te rt- butyl N-(6-hydroxyhexyl)carbamate (5.38 g, 24.8 mmol), triethylamine (5.01 g, 49.6 mmol) and 4-dimethylaminopyridine (151 mg, 1.24 mmol) in CH2CI2 (60 mL) was stirred at 0 C for 30 min, then /7-tolylsulfonylchloride (4.71 g, 24.8 mmol) was added in portions at 0 C. The resulting mixture was allowed to warm to rt and stirred at rt overnight. The mixture was diluted with water, and extracted with CH2CI2 for three times. The combined organic layers were washed with 1 M hydrochloric acid for three times, then washed with saturated NaHC03 aqueous solution and brine, dried over anhydrous Na2S04 and concentrated under reduced pressure to give 6-(ieri-butoxycarbonylamino)hexyl 4-methylbenzenesulfonate (8.30 g) as a yellow oil which was directly used in the next step without further purification.

Reference： [1]Magnetic Resonance in Chemistry,2013,vol. 51,p. 116 - 122
[2]Chemistry - A European Journal,2009,vol. 15,p. 3230 - 3242
[3]Organic Letters,2019,vol. 21,p. 9268 - 9271
[4]Tetrahedron,2003,vol. 59,p. 5749 - 5761
[5]Patent: US2014/371434,2014,A1 .Location in patent: Paragraph 0027; 0030; 0054
[6]Medicinal Chemistry,2016,vol. 12
[7]Journal of the Chemical Society. Chemical communications,1983,p. 162 - 164
[8]European Journal of Medicinal Chemistry,2017,vol. 127,p. 828 - 839
[9]Patent: WO2009/14997,2009,A2 .Location in patent: Page/Page column 9
[10]Patent: US2012/309797,2012,A1 .Location in patent: Paragraph 0117
[11]Patent: WO2013/36857,2013,A1 .Location in patent: Paragraph 0093
[12]Patent: US2015/210682,2015,A1 .Location in patent: Paragraph 1780; 1781
[13]Patent: WO2015/113990,2015,A1 .Location in patent: Page/Page column 266
[14]Patent: WO2016/177655,2016,A1 .Location in patent: Page/Page column 116; 117
[15]Patent: WO2017/17042,2017,A1 .Location in patent: Page/Page column 47; 48
[16]Chemistry - A European Journal,2018,vol. 24,p. 12370 - 12382

5
[ 75937-12-1 ]
[ 172846-36-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	With 1H-imidazole; iodine; triphenylphosphine; In dichloromethane; at 20℃; for 2h;	N-tert-Butoxycarbonyl-6-amino-1-iodohexane Triphenylphosphine (2.35 g, 8.96 mmol) and imidazole (0.61 g, 8.96 mmol) were dissolved in dichloromethane (15 ml), and the solution was stirred for 5 minutes. Then, iodine (2.28 g, 8.98 mmol) was added thereto, and the mixture was stirred for 10 minutes. A dichloromethane (4 ml) solution of N-tert-butoxycarbonyl-6-aminohexanol (1.3 g, 5.98 mmol) was added dropwise thereto, and the mixture was stirred at room temperature for 2 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was filtered through celite, and a 5% aqueous sodium thiosulfate solution was added to the filtrate to remove iodine. The organic layer was washed twice with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain N-tert-butoxycarbonyl-6-amino-1-iodohexane (1.67 g, yield: 86%).
80%	With 1H-imidazole; iodine; triphenylphosphine; In dichloromethane; at 20℃; for 2h;Inert atmosphere;	N-tert-Butoxycarbonyl-6-amino-1-iodohexane Triphenylphosphine (2.35 g, 8.96 mmol) and imidazole (0.61 g, 8.96 mmol) were dissolved in dichloromethane (15 ml), and the solution was stirred for 5 minutes. Then, iodine (2.28 g, 8.98 mmol) was added thereto, and the mixture was stirred for 10 minutes. A dichloromethane (4 ml) solution of N-tert-butoxycarbonyl-6-aminohexanol (1.3 g, 5.98 mmol) was added dropwise thereto, and the mixture was stirred at room temperature for 2 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was filtered through celite, and a 5% aqueous sodium thiosulfate solution was added to the filtrate to remove iodine. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain N-tert-butoxycarbonyl-6-amino-1-iodohexane (1.67 g, yield: 86%). alpha-Methyl-1-methoxycarbonyl-3-indoleacetic acid methyl ester was synthesized according to a method described in Katayama M, Kato Y, Marumo S. "Synthesis, absolute configuration and biological activity of both enantiomers of 2-(5,6-dichloro-3-indolyl)propionic acid: new dichloroindole auxins" Bioscience, Biotechnology, and Biochemistry, 65 (2), 270-276; 2001.

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 2581 - 2588
[2]Patent: US2015/353489,2015,A1 .Location in patent: Paragraph 0102; 0166; 0167
[3]Patent: US2019/224165,2019,A1 .Location in patent: Paragraph 0093; 0094; 0144-0145
[4]Journal of Organic Chemistry,2001,vol. 66,p. 4115 - 4121
[5]Journal of Medicinal Chemistry,2013,vol. 56,p. 2487 - 2499

6
[ 75937-12-1 ]
[ 80860-42-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium hydrogencarbonate; potassium bromide; In dichloromethane; water; for 1.2h;	Example 4; (Z)-6-(5H-Dibenzo[b,f]azepin-5-yl)hexan-1-sulfamate (15) Step 1: tert-Butyl 6-oxohexylcarbamate (12) To a stirred solution of 6-(Boc-amino)-hexanol (2.0 g, 9.2 mmol) and TEMPO (29 mg, 0.18 mmol) in DCM (20 ml) at 0 C. was added a 2.75 M KBr solution (7.3 ml) and a 1.6 M KHCO3 solution (32 ml). Then a 5.8% NaOCl (Javex) solution (15.9 ml) was added dropwise and stirred for 1.2 hour. A saturated Na2S2O3 solution was added and the mixture was extracted with DCM. The organic extract was dried (Na2SO4), filtered, and evaporated to afford 12 (2.0 g, quant.) as an oil. LRMS (ESI): (calc.) 215.2; (found) 216.2 (MH)+.
91%	With aluminum oxide; pyridinium chlorochromate; In dichloromethane; at 20℃; for 6h;Product distribution / selectivity;	Compound 2 (16 g) was dissolved in 500 mL of DCM and to it was added 24.0 g of PCC and 60 g of neutral alumina. The reaction mixture was stirred at room temperature, and the progress of the reaction was monitored by TLC. The reaction was complete after 6 hours. The reaction mixture was filtered, and the filtrate was washed with water several times. The organic layer was evaporated under reduced pressure, and the crude product was purified by flash chromatography using ethyl acetate:hexane (1 :3) as eluent to give 3 (14.4 g, 91%) as colourless oil.
80%	In dichloromethane;	(b) t-Butyl-(5-formylpentyl)carbamate Pyridinium dichromate (13.5 g, 0.036 mol) is added to a solution of t-butyl-(6-hydroxyhexyl)carbamate (5.88 g, 24 mmol) in dichloromethane (40 ml). After stirring for 24 hours, the reaction mixture is diluted with diethylether/pentane (1:1), filtered through Florisil and concentrated to yield t-butyl-(5-formylpentyl)carbamate (4.13 g, 80%).

75%		Anhydrous dimethyl sulfoxide (83 uL) was added dropwise to a stirred solution of oxalyl chloride (50 uL) in anhydrous dichloromethane (2 mL) at -78C. After stirring for 15 iii mutes, a solution of 6-(tert-butoxy-carbonylarnino)- I -hexanol (115 mg, 0.53 mmol) in anhydrous dichloromethane (1 niL) was added dropwise. The resulting mixture was stirred at-78C for 45 minutes. Triethylamine (368 uL) was added and the reaction was allowed to warm to room temperature. This solution was concentrated on a rotary evaporator to afford the titled compound as an off-white solid (86 mg, 75% yield) which was used without further purification.
75%	With oxalyl dichloride; dimethyl sulfoxide; In dichloromethane; at -78℃; for 0.75h;	Anhydrous dimethyl sulfoxide (83 uL) was added dropwise to a stirred solution of oxalyl chloride (50 uL) in anhydrous dichoromethane (2 mL) at -78C. After stirring for 15 minutes, a solution of 6-(tert-butoxy-carbonylamino)-1-hexanol (1 15 rag, 0,53 mmol) in anhydrous dichloromethane (1 mL) was added dropwise. The resulting mixture was stirred at -78C for 45 minutes. Triethylamine (368 uL) was added and the reaction was allowed to warm to room temperature. This solution was concentrated on a rotary evaporator to afford the titled compound as an off-white solid (86 mg, 75% yield) which was used without further purification.
71%	With sodium hydrogencarbonate; Dess-Martin periodane; In dichloromethane; for 2h;	Example 19 Tert-butyl (6-hydroxyhexyl)carbamate (275, 300 mg, 1.38 mmol), Dess-Martin periodinane (918 mg, 2.16 mmol), and sodium bicarbonate (1.6 g, 19.0 mmol) in methylene chloride (10 ml) was stirred for 2 h. The heterogeneous mixture was filtered and the filtrate was directly flash chromatographed on silica gel (12 g) with methylene chloride:ethyl acetate as the eluent 100:0 to 80:20 over 10 min to afford 210 mg (71% yield) of tert-butyl (6-oxohexyl)carbamate, 276, as a clear oil.
14%	With Dess-Martin periodane; In dichloromethane; for 2h;	[0533] Di-tert-butyl-dicarbonate (1.155 g, 5.29 mmol) was added to a solution of 6-amino-1-hexanol (541 mg; 4.62 mmol) and diisopropylethyl amine (0.25 mL) in THF (10 mL). The mixture was stirred at ambient temperature for 18 hours, after which time the volatile components were removed under reduced pressure. The residue was dissolved in CH2Cl2 (30 mL) and washed with brine (3×20 mL). The organic phase was dried (Na2SO4), filtered and removed on a rotovap to leave a crude yellow oil (1.090 g). [0534] Some of the above-obtained oil (220 mg, 1.01 mmol) was dissolved in CH2Cl2 (5 mL) and treated with Dess-Martin periodinane (455 mg, 1.07 mmol). After 2 hours, the reaction was diluted with diethyl ether (20 mL) and treated with 20% w/v Na2S2O3 (aq). The phases were separated after 10 minutes, and the aqueous phase was extraced with ether (3×10 mL). The combined organic phase was washed with 20% w/v Na2S2O3 (1×12 mL), saturated aqueous NaHCO3 (1×12 mL) and brine (1×12 mL). The organic phase was dried (MgSO4), filtered and removed under reduced pressure to give a crude colourless oil (172 mg). This oil was purified by column chromatography (1.75 cm OD, 14 g silica, 4:1 hexanes: ethyl acetate) to give 31 mg of desired intermediate (14%). 1H NMR (CDCl3) d 1.29-1.50 (m, 13H), 1.63 (pentet, 2H, J=7.4 Hz), 2.42 (td, 2H, J=7.2, 1.6 Hz), 3.06-3.12 (m, 2H), 4.57 (br s, 1H), 9.74 (s, 1H). [0535] Using the General Procedure B: To a stirred solution of [1-(2-(trimethylsilyl)ethoxymethyl)-(1H-benzimidazol-2-ylmethyl)]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (62 mg, 0.150 mmol) and N-(tert-butoxycarbonyl)-6-amino-1-hexanal (31 mg, 0.144 mmol) in CH2Cl2 (2.5 mL) was added NaBH(OAc)3 (66 mg, 0.311 mmol) and the mixture stirred for 24 hours to afford a crude yellow oil (91 mg). [0536] This oil (91 mg) was dissolved in 4N HCl (2 mL) and heated to 50 C. After 4 hours the reaction was allowed to cool. The reaction was basified with ION NaOH (final pH>13) and the aqueous phase was extracted with CH2Cl2 (8×7 mL). The organic phase was dried (Na2SO4), filtered and removed on a rotovap to give 52 mg crude yellow oil freebase. This oil was purified by radial chromatography on silica gel (40:1:1 CH2Cl2: CH3OH: NH4OH) to give 36 mg yellow film (66% yield over two steps). [0537] Using the General Procedure D: conversion of the freebase from above (36 mg) to the hydrobromide salt gave COMPOUND 51 as a white solid (53 mg, 84%). [0538] 1H NMR (D2O) delta 1.13-1.23 (m, 4H), 1.31-1.56 (m, 4H), 1.75-1.90 (m, 1H), 1.96-2.10 (m, 1H), 2.13-2.23 (m, 1H), 2.31-241 (m, 1H), 2.44-2.55 (m, 1H), 2.71-2.81 (m, 1H), 2.85 (t, 2H, J=7.8 Hz), 2.97-3.04 (m, 2H), 4.38 (d, 1H, J=17.0 Hz), 4.48-4.59 (m, 2H), 7.61 (dd, 2H, J=6.1, 3.1 Hz), 7.80 (dd, 2H, J=6.1, 3.0 Hz), 7.86 (dd, 1H, J=7.7, 5.9 Hz), 8.34 (d, 1H, J=8.3 Hz), 8.62 (d, 1H, J=5.7 Hz). 13C NMR (D2O) delta 20.39, 20.45, 25.81, 26.41, 27.07, 27.64, 28.14, 39.74, 48.67, 52.22, 60.95, 114.24 (2 carbons), 125.86, 126.88 (2 carbons), 131.01, 139.21, 140.49, 147.99, 151.55, 152.12. ES-MS m/z 378 (M+H) Anal Calc. for C23H31N5.3.1HBr.1.9H2O: C, 41.69; H, 5.77; N, 10.57; Br, 37.38. Found: C, 41.77; H, 5.60; N, 10.60; Br, 37.36.
	With pyridinium chlorochromate; In hexane; dichloromethane;	B. To a solution of 8.8 g of pyridinium chlorochromate in 250 ml of methylene chloride is added 8.8 g of 3 Angstrom molecular sieves. A solution of 7.4 g of N-tert-butoxycarbonyl-6-amino-1-hexanol in 50 ml of methylene chloride is added dropwise and the mixture stirred at room temperature for 2 hours. The reaction mixture is filtered through silica gel, washing with 40% ethylacetate in hexane, and the filtrate evaporated in vacuo to give 6-N-tert-butoxycarbonylaminohexanal.
		The inventors were unsuccessful in their attempts to prepare Fmoc-beta - homolysine with a single Boc protecting group on the side chain, starting from aldehyde 14. No Mannich reaction product could be obtained. Moreover, the synthesis of 14 from the corresponding mono-Boc-protected aminohexanol gave only low yields, perhaps because the urethane adds intramolecularly to the carbonyl carbon.
661 mg	With Dess-Martin periodane; In dichloromethane; at 20℃; for 25h;	To a stirred solution of crude 17 (1.92g) in dry CH2Cl2 (10mL) at 0C was added Dess-Martin periodinane (3.74g, 8.81mmol). The reaction mixture was stirred at room temperature for 25h. Slow addition of a mixture of saturated NaHCO3/saturated Na2S2O3 (1:1, 10mL) and stirred for another 30min. The two layers were separated, and the aqueous layer was extracted with EtOAc (3×10mL). The combined organic layers were washed with H2O (2×20mL) and saturated NaCl (20mL), dried over anhydrous MgSO4, filtered and concentrated to give the crude product as light yellow oil (2.03g). Purification by flash column chromatography on silica gel (hexanes/EtOAc, 6:4) gave the title compound as colorless liquid (661mg, 37% over 2 steps). Rf (hexanes/EtOAc, 6:4)=0.38; 1H NMR (500MHz, CDCl3): delta=9.76 (t, J=1.8Hz, 1H), 4.58 (bs, 1H), 3.16-3.06 (m, 2H), 2.43 (td, J=7.3, 1.6Hz, 2H), 1.65 (p, J=7.5Hz, 2H), 1.54-1.47 (m, 2H), 1.44 (s, 9H), 1.39-1.32 (m, 2H); 13C NMR (125.8MHz, CDCl3): delta=202.6, 156.1, 79.2, 43.8, 40.4, 30.0, 28.5, 26.4, 21.8; HRMS (ESI): m/z [M+ Na]+ calcd for C11H21NO3Na+: 238.1414; found: 238.1418; m/z [2M+Na]+ calcd for C22H42N2O6Na+: 453.2935; found: 453.2930.

Reference： [1]Patent: US2007/293530,2007,A1 .Location in patent: Page/Page column 77
[2]Journal of Medicinal Chemistry,1999,vol. 42,p. 2969 - 2976
[3]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5147 - 5160
[4]Patent: WO2009/86429,2009,A1 .Location in patent: Page/Page column 78; 83
[5]European Journal of Organic Chemistry,2012,p. 1223 - 1229
[6]Journal of Organic Chemistry,2012,vol. 77,p. 747 - 753
[7]Journal of Medicinal Chemistry,2011,vol. 54,p. 2165 - 2182
[8]Patent: US4374128,1983,A
[9]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2172 - 2176
[10]Patent: WO2018/49019,2018,A1 .Location in patent: Paragraph 302
[11]Patent: WO2019/173640,2019,A1 .Location in patent: Page/Page column 49
[12]Journal of the American Chemical Society,2016,vol. 138,p. 10766 - 10769
[13]Patent: US2014/363454,2014,A1 .Location in patent: Paragraph 0291; 0347
[14]Organic Letters,2019,vol. 21,p. 4433 - 4438
[15]Journal of Organic Chemistry,2016,vol. 81,p. 1416 - 1424
[16]Angewandte Chemie - International Edition,2016,vol. 55,p. 8571 - 8574
Angew. Chem.,2016,vol. 128,p. 8713 - 8716,4
[17]Angewandte Chemie - International Edition,2018,vol. 57,p. 11683 - 11687
Angew. Chem.,2018,vol. 130,p. 11857 - 11861,5
[18]Patent: US2003/220341,2003,A1 .Location in patent: Page/Page column 51
[19]Patent: US5332726,1994,A
[20]Patent: WO2007/112358,2007,A1 .Location in patent: Page/Page column 39
[21]Tetrahedron,2017,vol. 73,p. 3866 - 3877
[22]Journal of the American Chemical Society,2020,vol. 142,p. 726 - 732

7
[ 75937-12-1 ]
[ 117241-31-3 ]
6-tert-butoxycarbonylaminohexyl 3,4,5-tris-dodecyloxybenzoate [ No CAS ]

Reference： [1]Chemistry - A European Journal,2005,vol. 11,p. 5126 - 5135

8
[ 75937-12-1 ]
[ 603-35-0 ]
[ 142356-33-0 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; triethylamine; In dichloromethane;	A solution of bromine (1.60 g, 10 mmol) in dichloromethane (10 ml) was added to a solution of triphenyl phosphine (2.62 g, 10 mmol) and triethylamine (1.01 g, 10 mmol) in dichloromethane (10 ml) at 0 C. After stirring at 0 C. for 30 minutes, a solution of N-t-BOC-6-amino-hexan-1-ol (2.4 g) in dichloromethane (10 ml) was added dropwise. After stirring for 2 hours, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography eluding with 20%ethyl acetate/hexane to provide N-t-BOC-6-amino-1-bromohexane (2.5 g).

Reference： [1]Patent: US6878715,2005,B1

9
[ 75937-12-1 ]
[ 1938-58-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 93 percent / CBr₄, PPh₃ / toluene / Ambient temperature 2: 86 percent / ethanol / 4 h / 45 °C 3: 69 percent / 3 M aq. HCl / ethyl acetate / 15 h / Ambient temperature

Reference： [1]Keller; Haner [Helvetica Chimica Acta, 1993, vol. 76, # 2, p. 884 - 892]

10
[ 75937-12-1 ]
[ 65915-94-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine / toluene / 0.08 h / 0 °C 2: NaN₃ / tetrabutylammonium bromide / toluene; H₂O / 3 h / 60 °C 3: 91 percent / H₂, CHCl₃ / Pd-C / methanol / 1 h / 1551.4 Torr

Reference： [1]Mattingly, Phillip G. [Synthesis, 1990, p. 366 - 368]

11
C₂₆H₃₅N₅O₁₀S₂ [ No CAS ]
[ 75937-12-1 ]
N₁-Boc-N₄-Nbs-N₄-(3-propyl-1-Nbs-amino-1-(6-hexanyl-1-Boc-amino))-trans-1,4-diaminocyclohexane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; toluene; benzene; at 25℃; for 18h;Under argon;	N1-Boc-N4-Nbs-N4-(3-propyl-1-Nbs-amino-1-(6-hexanyl-1-Boc-amino))-trans-1,4-diaminocyclohexane To a solution of 56 mg (0.087 mmol) of N1-Boc-N4-Nbs-N4-(3-propyl-1-Nbs-amino)-trans-1,4-diaminocyclohexane dissolved in 3.0 mL of 1:3 CH2Cl2/benzene together with 30 mg (0.11 mmol) of Ph3P and 17 mg (0.080 mmol) of N6-Boc-aminohexanol at 25 C. under argon was added 22 L (0.11 mmol) of a 40% solution of DIAD in toluene. After addition was complete the reaction was stirred for an additional 18 hrs. The solution was evaporated to dryness and the crude oil was then purified on silica gel, eluting first with 8:2 Hexane/EtOAc, then with 1:1 Hexane/EtOAc, and finally with 48:48:4 Hexane/EtOAc/MeOH to give 53 mg (79%) of product as a clear oil (Rf 0.30 (48:48:4 Hexane/EtOAc/MeOH)).

Reference： [1]Patent: US2004/235960,2004,A1 .Location in patent: Page 8

12
[ 4048-33-3 ]
[ 24424-99-5 ]
[ 75937-12-1 ]
[ 603-35-0 ]
[ 142356-33-0 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; triethylamine; In sodium hydroxide; dichloromethane; water;	a) N-t-BOC-6-amino-1-bromohexane was first prepared by adding di-tert-butyldicarbonate (3.675 g, 16.4 mmol) to a solution of 6-aminohexan-1-ol (1.6 g, 13.66 mmol) in 10% aqueous sodium hydroxide solution (40 ml). After stirring for 4 hours, the mixture was treated with water (150 ml) and extracted with ethyl acetate (450 ml). The combined extracts were washed with water (250 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by a flash chromatography on silica gel eluding with 20% methanol/dichloromethane to provide N-t-BOC-6-amino-hexan-1-ol (2.4 g). A solution of bromine (1.60 g, 10 mmol) in dichloromethane (10 ml) was added to a solution of triphenyl phosphine (2.62 g, 10 mmol) and triethylamine (1.01 g, 10 mmol) in dichloromethane (10 ml) at 0 C. After stirring at 0 C. for 30 minutes, a solution of N-t-BOC-6-amino-hexan-1-ol (2.4 g) in dichloromethane (10 ml) was added dropwise. After stirring for 2 hours, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography eluding with 20%ethyl acetate/hexane to provide N-t-BOC-6-amino-1-bromohexane (2.5 g).
	With bromine; triethylamine; In aqueous sodium hydroxide; dichloromethane; water;	a) N-t-BOC-6-amino-1-bromohexane was first prepared by adding di-tert-butyldicarbonate (3.675 g, 16.4 mmol) to a solution of 6-aminohexan-1-ol (1.6 g, 13.66 mmol) in 10% aqueous sodium hydroxide solution (40 ml). After stirring for 4 hours, the mixture was treated with water (150 ml) and extracted with ethyl acetate (450 ml). The combined extracts were washed with water (250 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by a flash chromatography on silica gel eluding with 20% methanol/dichloromethane to provide N-t-BOC-6-amino-hexan-1-ol (2.4 g). A solution of bromine (1.60 g, 10 mmol) in dichloromethane (10 ml) was added to a solution of triphenyl phosphine (2.62 g, 10 mmol) and triethylamine (1.01 g, 10 mmol) in dichloromethane (10 ml) at 0 C. After stirring at 0 C. for 30 minutes, a solution of N-t-BOC-6-amino-hexan-1-ol (2.4 g) in dichloromethane (10 ml) was added dropwise. After stirring for 2 hours, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography eluding with 20% ethyl acetate/hexane to provide N-t-BOC-6-amino-1-bromohexane (2.5 g).

Reference： [1]Patent: US2002/28823,2002,A1
[2]Patent: US6774130,2004,B2

13
[ 13633-25-5 ]
[ 75937-12-1 ]
[ 928118-30-3 ]

Yield	Reaction Conditions	Operation in experiment
44%	With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In water; at 20℃; for 20h;	A solution of 4-phenylbutyl bromide (0.98 g, 4.6 mmol) and 44A (1.0 g, 4.6 mmol) in 10 mL of benzene was treated sequentially with Bu4NHSO4 (0.16 g, 0.46 mmol) and 50% aqueous NaOH (2.4 mL, 46 mmol, added slowly). After stirring at RT under N2 for 20 h, the solvent was removed. The reaction mixture was then diluted with H2O, extracted with EtOAc, washed with H2O (3×) and brine, dried over Na2SO4, and filtered. The filtrate was concentrated and chromatographed (5-10% EtOAc/hexanes) to provide 44B (0.7 g, 44%).

Reference： [1]Patent: US2007/93477,2007,A1 .Location in patent: Page/Page column 46-47

14
[ 106412-36-6 ]
[ 75937-12-1 ]

Reference： [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 1324 - 1327

15
[ 172846-36-5 ]
[ 75937-12-1 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 5040 - 5042

16
[ 75937-12-1 ]
[ 18162-48-6 ]
[ 1321591-53-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With 1H-imidazole; In dichloromethane; at 0 - 25℃; for 16.5h;	Example 63: tert-Butyl 6-(tert-butyldimethylsilyloxy)hexylcarbamate (1-64)To a solution of tert-butyl 6-hydroxyhexylcarbamate (21 mmol) in CH2C12 (30 ml) was added imidazole (27 mmol) at 0C. The reaction mixture was kept at 25 C and stirred for 20 min, then cooled to 0C. To the resulting reaction mixture was added tert-butyldimethylchlorosilane (23 mmol) dropwise over 30 min at 0C. The reaction mixture was allowed to warm to 25 C and stirred for 16 h and then filtered. The filtrate was washed with 1 N HC1 (2x25 ml) and brine (30 ml), dried over Na2S04, filtered and evaporated under reduced pressure. The residue was purified by Si02 flash column (eluent: petroleum ether and then CH2C12). Yield 6.53 g (87% yield).

Reference： [1]Chemistry - A European Journal,2014,vol. 20,p. 8210 - 8216
[2]Patent: WO2011/121105,2011,A1 .Location in patent: Page/Page column 55
[3]Chemistry - A European Journal,2018,vol. 24,p. 12370 - 12382

17
[ 75937-12-1 ]
[ 1338075-62-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: 1H-imidazole / dichloromethane / 16.5 h / 0 - 25 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 16 h / 0 - 25 °C 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 18 h / 0 - 25 °C 3.2: 1 h / Cooling with ice
	Multi-step reaction with 3 steps 1.1: 1H-imidazole / dichloromethane / 48 h / 0 - 20 °C / Inert atmosphere 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.75 h / 0 °C / Inert atmosphere 2.2: 20 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2011/121105, 2011, A1
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2021/53495, 2021, A1

18
[ 524-38-9 ]
[ 75937-12-1 ]
[ 1443054-86-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃;	To a solution of (6-hydroxyhexyl)carbamic acid tert-butyl ester [29] (730 mg, 3.36 mmol), triphenylphosphine (1.173 g, 4.48 mmol) and N-hydroxyphthalimide (731 mg, 4.48 mmol) in THF (45 mL) at 0 C, diisopropyl azodicarboxylate (906 mg, 4.48 mmol) was dropped. After stirring overnight at room temperature, the solvent was evaporated and the residue was purified by flash chromatography (hexane/ethylacetate 3:7 then hexane/ethylacetate 2:8) and successively crystallized from MeOH to give the title compound as a white solid (yield 82%); mp 166 C. Rf 0.34 (CH2Cl2/MeOH 95:5). 1H NMR (CDCl3) delta: 7.89-7.67 (m, 4H); 4.61 (brs, 1H); 4.15 (t, J=6.7Hz 2H); 3.18-3.00 (m, 2H); 1.41 (s, 9H); 1.85-1.20 (m, 8H). 13C NMR (CDCl3) delta 163.6, 156.0, 134.4 (×2), 128.9 (×2), 123.4 (×2), 78.3, 70.0, 40.4, 29.8, 28.4, 28.2, 28.0, 26.3, 25.2, 21.9. HRMS (ESI+): [M+Na]+calcd for C19H26N2NaO5 385.1734; found 385.1779. Anal. calcd for C19H26N2O5: C, 62.97; H, 7.23; N, 7.73. Found: C, 62.81; H, 7.02; N, 7.98.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 63,p. 387 - 400
[2]PLoS ONE,2018,vol. 13
[3]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 283 - 287

19
[ 5670-69-9 ]
[ 75937-12-1 ]
C₂₅H₃₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		0.36 g (15 mmol) of sodium hydride was washed three times with hexane and after purging with argon, 5.0 mL of dry DMF was added. At 0 C, 1.1 g (5.0 mmol) of alcohol 1 dissolved in 5.0 mL of dry DMF was added and stirred for 4 hours. 0.74 g (3.3 mmol) of diphenyl nitroethene dissolved in 5 mL of dry DMF was added and the mixture was stirred at 0 C for 12 hours. The mixture was separated/ partitioned with ethyl acetate and NaHCO 3 aq and washed with brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and then purified by silica gel column chromatography (ethyl acetate / hexane = 1/3) to obtain 1.2 g (2.7 mmol, 80%) of nitroalkane 2.

Reference： [1]Patent: JP2017/160163,2017,A .Location in patent: Paragraph 0122

20
C₁₅H₂₃NO₆S [ No CAS ]
[ 75937-12-1 ]
C₂₆H₄₄N₂O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 18h;	To a solution of 3 (0.700 g, 2.03 mmol), 6-(Boc-amino)-1 -hexanol (0.530 g, 2.44 mmol) and PP i3 (0.640 g, 2.44 mmol) in anhydrous THF (36 imL) was added slowly diisopropyl azodicarboxylate (0.480 imL, 2.44 mmol). After 18 h at room temperature, the reaction mixture was concentrated and the crude product was dispersed in a 8:1 mixture of petroleum ethenethyl acetate. The dispersion was filtered and the solid was purified by flash chromatography on silica gel (CH2CI2:Acetone 40:1 ) to yield 4 as glassy white solid (0.922 g, 83%). . [ 25 +15.17 (c 0.6, CHCI3); ESI-MS 567.20 [M+Na]+; 1 H NMR (500 MHz, CDCI3): delta 7.81 -7.78 (AlphaAlpha' part of an AA'MM' system, JAM= 9.0 Hz, 2H), 6.97-6.93 (MM' part of an AA'MM' system, JMA = 9.0 Hz, 2H), 4.67 (t, J2,i = 5.3 Hz, 1 H, H-2), 4.56-4.50 (bs, 1 H, NH), 3.88 (s, 3H, PhOCHs), 3.77 (d, Ji,2 = 5.4 Hz, 2H, H-1 ), 3.61 (s, 3H, COOCH3), 3.30- 3.19 (m, 2H, CH2N), 3.1 1 -3.09 (m, 2H, CH2N), 1 .73-1 .56 (m, 2H, CH2CH2N), 1 .46 (s, 1 1 H, tBu, CH2CH2N), 1 .34-1 .20 (m, 4H, H-5, H-6), 1 .14 (s, 9H, Boc). 13C NMR (125 MHz, CDCI3): delta 170.1 (Cq), 162.7 (Cq), 156.0 (Cq), 132.1 (Cq), 129.6 (CH Ar), 1 13.8 (CH Ar), 61 .5 (C-1 ), 60.2 (C-2), 55.6 (PhOCHs), 52.0 (COOCH3), 46.8 (CH2N), 40.5 (CH2N), 30.5 (CH2CH2N), 30.0 (CH2CH2N), 28.4 (tBu), 27.3 (Boc), 26.6-26.5 (C-5, C-6).

Reference： [1]Patent: WO2018/29588,2018,A1 .Location in patent: Page/Page column 9

21
[ 75937-12-1 ]
tert-butyl (6-fluorohexyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%		To a solution of 1.0 g (4.6 mmol, 1 eq.) of of tert-butyl(6-hydroxyhexyl)carbamate and 1.15 mL (8.3 mmol, 1.8 eq.) of triethylamine in 18 mL of anhydrous DCM were added 0.53 mL of methanesulfonyl chloride (6.9 mmol, 1.5 eq.). The mixture was stirred at room temperature for 2 hours. The mixture was washed with water and extracted with dichloromethane. The organic layer was dried over Na2S04, filtered and concentrated in vacuo. The residue was dissolved in i-BuOH (48 mL) and 3.5 g (23.0 mmol, 5.0 eq) of cesium fluoride were added. The suspension was refluxed for 16 hours. After cooling to room temperature, diethylether was added and the suspension filtered. The filtrate was concentrated in vacuo. The residue was purified by flash chromatography (DCM) to afford 776 mg of E as a colorless oil. Yield 77%. IR vmax3354, 2970, 2934, 2866, 1691, 1516, 1364, 1250, 1168, 1045, 984 cm"1. NMR 1H (400 MHz; CDC13) deltaEta4.43 (2H, dt, J = 47.3, 6.1 Hz), 3.11 (2H, q, J = 6.7 Hz), 1.68 (2H, ddt, J = 25.2, 8.1, 6.2 Hz), 1.53-1.33 (6H, m), 1.44 (9H, s). NMR13C (100 MHz; CDC13) 5C156.1, 84.2 (d, J = 164 Hz), 79.2, 40.6, 30.5 (d, J = 20 Hz), 30.1, 28.6, 26.6, 25.1 (d, J = 5.4 Hz). MS (ESI+): calcd for C22H45F2N204[(2M+H)+]: 439.3; Found: 439.3.

Reference： [1]Patent: WO2019/86614,2019,A1 .Location in patent: Page/Page column 47; 73; 80

22
[ 75937-12-1 ]
[ 1013915-06-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0.5 h / 0 - 15 °C 2: ethanol / 16 h / 80 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 5 h / 0 - 20 °C 2: triethylamine / 1,4-dioxane; water monomer / 1 h / 60 °C
	Multi-step reaction with 3 steps 1: triethylamine; dmap / dichloromethane / 0 - 20 °C 2: potassium carbonate; sodium iodide / acetonitrile / 80 °C / Inert atmosphere 3: palladium on activated charcoal; hydrogen / methanol / 40 °C

Multi-step reaction with 2 steps 1.1: Dess-Martin periodane / dichloromethane / 2 h 2.1: methanol; ethanol / 3 h 2.2: 0.5 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: KYMERA THERAPEUTICS INC - WO2020/113233, 2020, A1
[2]Labriere, Christophe; Elumalai, Vijayaragavan; Staffansson, Jannie; Cervin, Gunnar; Le Norcy, Tiffany; Denardou, Hugo; Réhel, Karine; Moodie, Lindon W. K.; Hellio, Claire; Pavia, Henrik; Hansen, Jørn H.; Svenson, Johan [Journal of Natural Products, 2020, vol. 83, # 11, p. 3413 - 3423]
[3]Current Patent Assignee: REYOUNG DRUG DISCOVERY; REYOUNG - WO2021/142065, 2021, A1
[4]Current Patent Assignee: BACAINN BIOTHERAPEUTICS - WO2022/5881, 2022, A1

23
[ 75937-12-1 ]
[ 1426551-76-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 1.2: 48 h / Inert atmosphere; Reflux 2.1: trifluoroacetic acid / dichloromethane / 3 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 2: lithium bromide / acetonitrile; N,N-dimethyl-formamide / 48 h / Inert atmosphere; Reflux 3: trifluoroacetic acid / dichloromethane / 3 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: UNIVERSITY OF PENNSYLVANIA; WISTAR INSTITUTE - WO2021/202540, 2021, A1
[2]Current Patent Assignee: UNIVERSITY OF PENNSYLVANIA; WISTAR INSTITUTE - WO2021/202540, 2021, A1

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

[ CAS No. 75937-12-1 ] {[proInfo.proName]}

Quality Control of [ 75937-12-1 ]

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[ 75937-12-1 ] Synthesis Path-Upstream 1~4

[ 75937-12-1 ] Synthesis Path-Downstream 1~23

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Amino Acid Derivatives

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[ 75937-12-1 ]