Name: 172348-63-9|tert-Butyl ((trans-4-(hydroxymethyl)cyclohexyl)methyl)carbamate|98%
Brand: Ambeed
SKU: A123999
Price: 9.0 USD
Availability: InStock
Rating: 93 (30 reviews)

1
[ 27687-14-5 ]
[ 172348-63-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With borane-THF In tetrahydrofuran at 20℃; for 2h;	132 [0406] t-Butyl (((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)aminoformate, synthesized according to the examples mentioned above, with a yield of 85%. LC/MS (ESI+) calcd for : C13H25NO3 (M + H+) m/z, 244.3; found, 188.3.
85%	With borane-THF In tetrahydrofuran at 20℃; for 2h;	132 [0406] t-Butyl (((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)aminoformate, synthesized according to the examples mentioned above, with a yield of 85%. LC/MS (ESI+) calcd for : C13H25NO3 (M + H+) m/z, 244.3; found, 188.3.
85%	With borane-THF In tetrahydrofuran at 20℃; for 2h;	132 [0406] t-Butyl (((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)aminoformate, synthesized according to the examples mentioned above, with a yield of 85%. LC/MS (ESI+) calcd for : C13H25NO3 (M + H+) m/z, 244.3; found, 188.3.

52%	With lithium aluminium hydride In tetrahydrofuran; 1,4-dioxane
	Multi-step reaction with 2 steps 1: Et₃N / CH₂Cl₂ / 0.83 h / 0 °C 2: NaBH₄ / tetrahydrofuran; methanol / 3 h / 4 °C
	With borane-THF In tetrahydrofuran at 0 - 20℃; for 6h;	33.A Step A : Synthesis of tert-butyl ((lr,4r)-4-(hydroxymethyl)cyclohexyl)methylcarbamate Borane (7.77 mL, 15.5 mmol) was added dropwise to a stirred solution of (lr,4r)- 4-(((tert-butoxycarbonyl)amino)methyl)cyclohexanecarboxylic acid (2.0 g, 7.77 mmol) in THF (20 ml) at 0°C. After the reaction mixture was stirred for 6 hr at ambient temperature, it was quenched with water (20 mL) and extracted with EtOAc (2 x 40 mL). The combined organic layers were washed brine (2 x 30 mL), dried over anhydrous Na2S04 and concentrated under vacuum to afford the title compound: XH NMR (400 MHz, CDC13) δ 4.60-4.50 (brs, 1H), 3.46 (d, J= 6.4 Hz, 2H), 3.01-2.98 (m, 2H), 1.90-1.82 (m, 4H), 1.81-1.80 (m, 1H ), 1.46 (brs, 9H), 1.45- 1.42 (m, 2H), 1.02-097(m, 4H).

Reference： [1]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1 Location in patent: Paragraph 0404; 0406
[2]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1 Location in patent: Paragraph 0404; 0406
[3]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1 Location in patent: Paragraph 0404; 0406
[4]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]
[5]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]
[6]Current Patent Assignee: MERCK & CO INC - WO2015/112441, 2015, A1 Location in patent: Page/Page column 78

2
[ 172348-63-9 ]
[ 180046-90-6 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: tert-butyl (((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)carbamate With triethylamine In dichloromethane Stage #2: With pyridine-SO₃ complex In dichloromethane; dimethyl sulfoxide at 0℃; for 2h;
	With Dess-Martin periodane In dichloromethane at 20℃; for 3h;

Reference： [1]Jecs, Edgars; Miller, Eric J.; Wilson, Robert J.; Nguyen, Huy H.; Tahirovic, Yesim A.; Katzman, Brook M.; Truax, Valarie M.; Kim, Michelle B.; Kuo, Katie M.; Wang, Tao; Sum, Chi S.; Cvijic, Mary E.; Schroeder, Gretchen M.; Wilson, Lawrence J.; Liotta, Dennis C. [ACS Medicinal Chemistry Letters, 2018, vol. 9, # 2, p. 89 - 93]
[2]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

3
C₁₆H₂₇NO₆ [ No CAS ]
[ 172348-63-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate In tetrahydrofuran; methanol at 4℃; for 3h;

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

4
[ 98-59-9 ]
[ 172348-63-9 ]
[ 178972-34-4 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 4 - 20℃; for 15h;

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

5
[ 24424-99-5 ]
[ 172348-63-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 67 percent / aq. NaOH / 2-methyl-propan-2-ol / 18 h / 20 °C 2: Et₃N / CH₂Cl₂ / 0.83 h / 0 °C 3: NaBH₄ / tetrahydrofuran; methanol / 3 h / 4 °C
	Multi-step reaction with 2 steps 1: aq. NaOH / dioxane / 20 °C 2: 52 percent / LiAlH₄ / dioxane; tetrahydrofuran

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]
[2]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

6
[ 1197-18-8 ]
[ 172348-63-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 67 percent / aq. NaOH / 2-methyl-propan-2-ol / 18 h / 20 °C 2: Et₃N / CH₂Cl₂ / 0.83 h / 0 °C 3: NaBH₄ / tetrahydrofuran; methanol / 3 h / 4 °C
	Multi-step reaction with 2 steps 1: aq. NaOH / dioxane / 20 °C 2: 52 percent / LiAlH₄ / dioxane; tetrahydrofuran
	Multi-step reaction with 2 steps 1: triethylamine / lithium hydroxide monohydrate; 1,4-dioxane / Cooling with ice 2: borane-THF / tetrahydrofuran / 2 h / 20 °C

Multi-step reaction with 2 steps 1: borane-THF / tetrahydrofuran / 20 °C / Inert atmosphere 2: triethylamine / 1,4-dioxane / 6 h / 20 °C

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]
[2]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]
[3]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1
[4]Current Patent Assignee: HINOVA PHARMACEUTICALS - EP3971176, 2022, A1

7
[ 172348-63-9 ]
[ 192323-08-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

8
[ 172348-63-9 ]
(4-aminomethyl-cyclohexylmethyl)-quinazolin-2-yl-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C 3: 91 percent / lithium aluminum hydride / tetrahydrofuran / 6 h / 20 °C 4: propan-2-ol / Heating 5: HCl / ethyl acetate / 1.5 h / 20 °C

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

9
[ 172348-63-9 ]
N²-(4-aminomethyl-cyclohexylmethyl)-N⁴,N⁴-dimethyl-quinazoline-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C 3: 91 percent / lithium aluminum hydride / tetrahydrofuran / 6 h / 20 °C 4: propan-2-ol / Heating 5: HCl / ethyl acetate / 1.5 h / 20 °C

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

10
[ 172348-63-9 ]
[ 853799-80-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C 3: 91 percent / lithium aluminum hydride / tetrahydrofuran / 6 h / 20 °C 4: propan-2-ol / Heating

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

11
[ 172348-63-9 ]
[ 192323-09-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C 3: 91 percent / lithium aluminum hydride / tetrahydrofuran / 6 h / 20 °C 4: propan-2-ol / Heating

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

12
[ 172348-63-9 ]
[ 509142-38-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C 3: 91 percent / lithium aluminum hydride / tetrahydrofuran / 6 h / 20 °C 4: propan-2-ol / Heating

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

13
[ 172348-63-9 ]
[ 166168-16-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C 3: 91 percent / lithium aluminum hydride / tetrahydrofuran / 6 h / 20 °C

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

14
[ 172348-63-9 ]
[ 749866-16-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: pyridine / 15 h / 4 - 20 °C 2: NaN₃ / dimethylformamide / 4 h / 50 °C 3: 91 percent / lithium aluminum hydride / tetrahydrofuran / 6 h / 20 °C 4: propan-2-ol / Heating 5: HCl / ethyl acetate / 1.5 h / 20 °C

Reference： [1]Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Semple, Graeme; Tran, Thuy-Anh; Kramer, Bryan; Hsu, Debbie; Casper, Martin; Thomsen, Bill; Beeley, Nigel; Sekiguchi, Yoshinori [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 10, p. 2565 - 2569]

15
[ 172348-63-9 ]
[(4-aminomethyl-cyclohexyl)-benzyloxycarbonylamino-methyl]-phosphonic acid diphenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2: Cu(OTf)2 / methanol / 4 h / 20 °C 3: TFA / CH₂Cl₂ / 3 h / 20 °C

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

16
[ 172348-63-9 ]
trans diphenyl benzyloxycarbonylamino-(4-(tert-butyloxycarbonylaminoethyl)cyclohexyl)methanephosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2: Cu(OTf)2 / methanol / 4 h / 20 °C

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

17
[ 172348-63-9 ]
C₃₁H₄₅N₄O₇P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2: Cu(OTf)2 / methanol / 4 h / 20 °C 3: TFA / CH₂Cl₂ / 3 h / 20 °C 4: 41 percent / TEA / acetonitrile / 20 °C 5: H₂ / Pd/C / methanol / 8 h / 20 °C

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

18
[ 172348-63-9 ]
C₃₄H₅₀N₅O₈P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2.1: Cu(OTf)2 / methanol / 4 h / 20 °C 3.1: TFA / CH₂Cl₂ / 3 h / 20 °C 4.1: 41 percent / TEA / acetonitrile / 20 °C 5.1: H₂ / Pd/C / methanol / 8 h / 20 °C 6.1: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium*BF₄; TEA / dimethylformamide / 0.17 h / 20 °C 6.2: 21 percent / dimethylformamide 7.1: H₂ / Pd/C / methanol / 8 h / 20 °C

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

19
[ 172348-63-9 ]
trans diphenyl benzyloxycarbonylamino-(4-((N,N'-bis(tert-butyloxycarbonyl)guanyl)methyl)cyclohexyl)methanephosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2: Cu(OTf)2 / methanol / 4 h / 20 °C 3: TFA / CH₂Cl₂ / 3 h / 20 °C 4: 41 percent / TEA / acetonitrile / 20 °C

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

20
[ 172348-63-9 ]
trans diphenyl N-(N-benzyloxycarbonyl-L-alanyl)amino-(4-((N,N'-bis(tert-butyloxycarbonyl)guanyl)methyl)cyclohexyl)methanephosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2.1: Cu(OTf)2 / methanol / 4 h / 20 °C 3.1: TFA / CH₂Cl₂ / 3 h / 20 °C 4.1: 41 percent / TEA / acetonitrile / 20 °C 5.1: H₂ / Pd/C / methanol / 8 h / 20 °C 6.1: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium*BF₄; TEA / dimethylformamide / 0.17 h / 20 °C 6.2: 21 percent / dimethylformamide

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

21
[ 172348-63-9 ]
trans diphenyl N-(N-benzyloxycarbonyl-D-seryl-L-alanyl)amino-(4-(guanylmethyl)cyclohexyl)methanephosphonate trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2.1: Cu(OTf)2 / methanol / 4 h / 20 °C 3.1: TFA / CH₂Cl₂ / 3 h / 20 °C 4.1: 41 percent / TEA / acetonitrile / 20 °C 5.1: H₂ / Pd/C / methanol / 8 h / 20 °C 6.1: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluroniumBF₄; TEA / dimethylformamide / 0.17 h / 20 °C 6.2: 21 percent / dimethylformamide 7.1: H₂ / Pd/C / methanol / 8 h / 20 °C 8.1: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluroniumBF₄; TEA / dimethylformamide / 0.17 h / 20 °C 8.2: 29 percent / dimethylformamide 9.1: 97 percent / TFA / CH₂Cl₂ / 3 h / 20 °C

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

22
[ 172348-63-9 ]
trans diphenyl ((N-benzyloxycarbonyl-O-tert-butyl-D-seryl)-L-alanyl)amino-(4-((N,N'-bis(tert-butyloxycarbonyl)guanyl)methyl)cyclohexyl)methanephosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: Dess-Martin periodane / CH₂Cl₂ / 3 h / 20 °C 2.1: Cu(OTf)2 / methanol / 4 h / 20 °C 3.1: TFA / CH₂Cl₂ / 3 h / 20 °C 4.1: 41 percent / TEA / acetonitrile / 20 °C 5.1: H₂ / Pd/C / methanol / 8 h / 20 °C 6.1: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluroniumBF₄; TEA / dimethylformamide / 0.17 h / 20 °C 6.2: 21 percent / dimethylformamide 7.1: H₂ / Pd/C / methanol / 8 h / 20 °C 8.1: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluroniumBF₄; TEA / dimethylformamide / 0.17 h / 20 °C 8.2: 29 percent / dimethylformamide

Reference： [1]Joossens; Van Der Veken; Lambeir; Augustyns; Haemers [Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413]

23
[ 178972-33-3 ]
[ 24424-99-5 ]
[ 172348-63-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium carbonate In 1,4-dioxane; dichloromethane; water	4 N-tert-Butoxycarbonyl-trans-4-(aminomethyl)cyclohexanemethanol N-tert-Butoxycarbonyl-trans-4-(aminomethyl)cyclohexanemethanol Sodium carbonate (1.33 g, 12.4 mmol.) was added to a solution of trans-4-(aminomethyl)cyclohexanemethanol hydrochloride (1.5 g, 8.3 mmol.) in 1:1 dioxane:water (40 mL). Di-tert-butyl dicarbonate (2.0 g, 9.13 mmol.) was added to the reaction mixture at 0° C. The reaction mixture was stirred at room temperature for 5 hours then partitioned between 10% methanol in dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate and concentrated. N-tert-Butoxycarbonyl-trans-4-(aminomethyl)cyclohexanemethanol (1.97 g, 98% yield)was obtained as a white solid. 1 H NMR (CDCl3): 4.58 (br, 1H), 3.44 (d, 2H), 2.95 (tr, 2H), 1.81 (m, 4H), 1.54 (m, 2H), 1.44 (s, 9H), 0.92 (tr, 4H)

Reference： [1]Current Patent Assignee: QUEST DIAGNOSTICS INC - US6022969, 2000, A

24
[ 558-13-4 ]
[ 172348-63-9 ]
N-(trans-4-bromomethyl-1-cyclohexylmethyl)-N-(tert-butoxycarbonyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine In dichloromethane	R.37.3 3) 3) Synthesis of N-(trans-4-bromomethyl-1-cyclohexylmethyl)-N-(tert-butoxycarbonyl)amine To a solution of 5.00 g (20.55 mM) of trans-4-[N-(tert-butoxycarbonyl)aminomethyl]cyclohexane-1-methanol and 6.42 g (24.48 mM) of triphenylphosphine in methylene chloride (30 ml) was added 13.63 g (41.1 mM) of carbon tetrabromide at 0° C. and the mixture was stirred at room temperature for 20 hours. This reaction mixture was purified by column chromatography (ethyl acetate-hexane: 10%) to provide the title compound as white solid. Yield 2.53 g (40%) 1H-NMR (200 MHz, CDCl3) δ: 0.83-1.14 (m, 4H), 1.44 (s, 9H), 1.49-1.70 (m, 2H), 1.71-2.01 (m, 4H), 2.98 (t, J=6.4 Hz, 2H), 3.28 (d, J=6.2 Hz, 2H), 4.47-4.66 (m, 1H). IR (KBr): 3390, 2921, 1685, 1524, 1257, 1174, 613 cm-1.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US6235731, 2001, B1

25
borane-THF [ No CAS ]
[ 27687-14-5 ]
[ 172348-63-9 ]

Yield	Reaction Conditions	Operation in experiment
96.7%	With sodium chloride In water	R.37.2 2) 2) Synthesis of trans-4-[N-(tert-butoxycarbonyl)aminomethyl]cyclohexane-1-methanol To 400 ml of 1.0M borane-THF was added 51.7 g (200 mM) of trans-4-[N-(tert-butoxycarbonyl)aminomethyl]cyclohexane-1-carboxylic acid in small portions at 0° C. and the mixture was stirred at room temperature for 2 hours. This reaction mixture was then poured in iced water and, after thorough stirring, extracted with 200 ml of ethyl acetate. The organic layer was washed with 250 ml of saturated aqueous solution of sodium chloride and dried over MgSO4 and the solvent was distilled off under reduced pressure to provide 47.06 g (yield 96.7%) of crude product as white solid. This crude product was not purified but used as it was in the next reaction. 1H-NMR (200 MHz, DMSO-d6) δ: 0.74-0.96 (m, 4H), 1.14-1.45 (m, 11H), 1.62-1.81 (m, 4H), 2.76 (t, 2H, J=6.2 Hz), 3.20 (t, 2H, J=6.0 Hz), 4.31 (t, 1H, OH, J=6.0 Hz), 6.72 (t, 1H, J=5.4 Hz). IR (KBr): 3376, 1698, 1533 cm-1.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US6235731, 2001, B1

26
[ 623-73-4 ]
[ 172348-63-9 ]
[ 1187857-60-8 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃;	1.97.D Step C: Preparation of Ethyl 2-(((lr,4r)-4-((tert- Butoxycarbonylamino)methyl)cyclohexyl)methoxy)acetate; To a solution of tert-butyl ((lr,4r)-4-(hydroxymethyl)cyclohexyl)methylcarbamate (500 mg, 2.055 mmol) and rhodium(II) acetate (45.4 mg, 0.103 mmol) in DCM (5.0 mL) was added dropwise a solution of ethyl 2-diazoacetate (0.213 mL, 2.055 mmol) in DCM (10 mL). The resulting solution was stirred at room temperature overnight. The reaction was quenched with water; the organic layer was washed with water (twice) and brine, dried over MgSO4 and concentrated. The residue was purified by preparative LCMS to provide the title compound as a white solid. (244 mg). LCMS m/z = 330.2 [M+H]+; 1H νMR (400 MHz, DMSO-J6) δ ppm 0.78- 0.97 (m, 4H), 1.22 (t, J= 7.07 Hz, 3H), 1.29 (bs, IH), 1.39 (s, 9H), 1.48 (bs, IH), 1.66-1.79 (m, 4H), 2.78 (t, J = 6.32 Hz, 2H), 3.28 (d, J= 6.57 Hz, 2H), 4.07 (s, 2H), 4.13 (q, J= 7.07 Hz, 2H), 6.81 (t, J= 5.81 Hz, IH).

Reference： [1]Current Patent Assignee: PFIZER INC; ARENA PHARM INC - WO2009/117095, 2009, A1 Location in patent: Page/Page column 160

27
[ 5292-43-3 ]
[ 172348-63-9 ]
[ 1187857-15-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: tert-butyl (((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)carbamate With sodium hydride In tetrahydrofuran at 20℃; Cooling; Stage #2: bromoacetic acid <i>tert</i>-butyl ester In tetrahydrofuran at 20 - 60℃;	1.78.A Example 1.78: Preparation of 2-(((lr,4r)-4-((3,3-Diphenylureido)methyl)cyclohexyl)methoxy)acetic Acid (Compound 2).; Step A: Preparation of terf-Butyl 2-(((lr,4r)-4-((tert-Butoxycarbonylamino)methyl)cyclohexyl)methoxy)acetate.; A cooled solution of /er/-butyl ((lr,4r)-4-(hydroxymethyl)cyclohexyl)methylcarbamate (2.0 g, 8.22 mmol) in THF (30 mL) was treated with NaH (60% dispersion in mineral oil, 1.315 g, 32.9 mmol). The resulting suspension was stirred at room temperature for 1 h then /erf-butyl 2-bromoacetate (1.822 mL, 12.33 mmol) was added. The reaction was heated in the microwave to 60 °C for 1 h and then left stirring overnight at room temperature. Additional tert-butyl 2- bromoacetate (975 μL) was added and the reaction was heated to 60 0C and stirred for 2 h. The reaction was quenched with water and extracted with DCM. The combined DCM extract was washed with water; dried over MgSO4 and concentrated. The resulting residue was purified by preparative LCMS to provide the title compound as a white solid (0.250 g). LCMS m/z = 380.4 [M+Na]+; 1H NMR (400 MHz, DMSO-^6) δ ppm 0.78-0.96 (m, 4H), 1.29 (bs, IH), 1.39 (s, 9H), 1.44 (s, 9H), 1.66-1.79 (m, 4H), 2.78 (t, J= 6.32 Hz, 2H), 3.26 (, J= 6.32 Hz, 2H), 3.94 (s, 2H), 6.80 (t, 7= 5.68 Hz, IH).

Reference： [1]Current Patent Assignee: PFIZER INC; ARENA PHARM INC - WO2009/117095, 2009, A1 Location in patent: Page/Page column 152-153

28
[ 35059-50-8 ]
[ 172348-63-9 ]
[ 1187857-15-3 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃;	1.80.B Step B: Preparation of te/t-Butyl 2-(((lr,4r)-4-((tert- Butoxycarbonylamino)methyl)cyclohexyl)methoxy)acetate.; To a solution ((lr,4r)-4-(hydroxymethyl)cyclohexyl)methylcarbamate (1.0 g, 4.11 mmol) and rhodium(H) acetate (0.091 g, 0.205 mmol) in dichloromethane (10 mL) was added dropwise a solution of tert-butyl 2-diazoacetate (0.584 g, 4.11 mmol) in dichloromethane (10 mL). The resulting solution was stirred at room temperature overnight. The reaction was quenched with water; the organic layer was subsequently washed with water (twice) and brine; dried over MgSO4 and concentrated. The residue was purified by preparative LCMS to provide the title compound as a white solid (571 mg). LCMS m/z = 380.4 [M +Na]+; 1H NMR (400 MHz, DMSO-J6) δ ppm 0.78-0.97 (m, 4H), 1.29 (bs, IH), 1.39 (s, 9H), 1.44 (s, 9H), 1.66-1.79 (m, 4H), 2.78 (t, J= 6.32 Hz, 2H), 3.26 (d, J= 6.32 Hz, 2H), 3.94 (s, 2H), 6.80 (t, J= 5.68 Hz, IH).

Reference： [1]Current Patent Assignee: PFIZER INC; ARENA PHARM INC - WO2009/117095, 2009, A1 Location in patent: Page/Page column 154

29
1H-pyrazolo[3,4-d]pyrimidin-6-amine [ No CAS ]
[ 172348-63-9 ]
tert-butyl (trans-4-((6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexyl)methylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 16h;	A.1.1 Illustration of General Procedure A; Preparation No.A.1.1: teri-Butyl (ir«KS-4-((6-chloro-l/ -pyrazolo[3,4-i/\|pyrimidin-l- yl)methyl)cyclohexyl)methylcarbamate; Diethyl azodicarboxylate (1.33 mL, 3.35 mmol) was added drop-wise over about 2 min to a 250 mL round-bottomed flask charged with 6-chloro-l//-pyrazolo[3,4-J]pyrimidine (0.345 g, 2.23 mmol, Preparation No.2), teri-butyl (ira«s-4-hydroxymethyl) cyclohexyl)methylcarbamate (0.815 g, 3.35 mmol, AMRI), and triphenylphosphine (0.703 g, 2.68 mmol) in THF (20 mL). The reaction was allowed to stir for about 16 h at ambient temperature then concentrated under reduced pressure and the crude product was purified by silica gel chromatography eluting with 35% EtOAc in heptane to provide tert-butyl (trans-4-((6-chloro-lH-pyrazolo[3,4-d]pyrimidin-l- yl)methyl)cyclohexyl)methylcarbamate (0.835 g, 98%>) as a white solid. LC/MS (Table 2, Method a) R, = 2.59 min; MS m/z: 381 (M+H)+.

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2011/156698, 2011, A2 Location in patent: Page/Page column 53-54

30
[ 172348-63-9 ]
tert-butyl (((1r,4r)-4-(iodomethyl)cyclohexyl)methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-imidazole; iodine; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 12h;	33.B Step B : Synthesis of tert-butyl ((lr,4r)-4-(iodomethyl)cyclohexyl)methylcarbamate L (2.253 g, 8.88 mmol) in 10 mlTHF was added dropwise to a stirred mixture of tert-butyl (((lr,4r)-4-(hydroxymethyl)cyclohexyl)methyl)carbamate (1.8 g, 7.40 mmol), triphenylphosphine (2.328 g, 8.88 mmol) andlH-imidazole (0.604 g, 8.88 mmol) in THF (30 ml) at 0°C. The reaction mixture was stirred 12 hr at ambient temperature and then quenched with water (50 mL) and extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with a2S03 (aq.) ( 2 x 50 mL), dried over anhydrous Na2S04 and concentrated under vacuum. The residue was purified by silica gel chromatography, eluted with EtOAc/PE (1/5) to give the title compound: XH NMR (400 MHz, CDC13) δ 4.70-4.60 (m, 1H), 3.10 (dd, J= 6.4 Hz, 2H), 2.99 (dd, J= 6.4 Hz, 2H), 1.94-1.92 (m, 2H), 1.80-1.78 (m, 2H), 1.45 (brs, 9H ), 1.42-1.39 (m, 2H), 1.04-0.97 (m,4H).
	With 1H-imidazole; triphenylphosphine In diethyl ether; acetonitrile at 0 - 20℃;	457.A Step A: tert-butyl (((1r,4r)-4-(iodomethyl)cyclohexyl)methyl)carbamate Step A: tert-butyl (((1r,4r)-4-(iodomethyl)cyclohexyl)methyl)carbamate (0963) Triphenylphosphine (701 mg, 2.67 mmol) and tert-butyl (((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)carbamate (500 mg, 2.055 mmol) in acetonitrile (2.5 ml) and diethyl ether (7.5 ml) were added imidazole (182 mg, 2.67 mmol) at 0° C., and then stirred at room temperature for 15 minutes. tert-Butyl (((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)carbamate (500 mg, 2.055 mmol) in the same solvent system (2 mL) was added dropwise at 0° C. After finished, the solution was stirred at rt overnight. The reaction mixture was evaporated, and added DCM (5 mL). The suspension was filtered and evaporated to get the crude product. The crude was purified by column chromatography on silica gel, eluting with 0-10% MeOH/DCM (254 nm has weak absorption, out early) to give the desired product. LC-MS (IE, m/z): 354.32 [M+1]+

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/112441, 2015, A1 Location in patent: Page/Page column 78; 79
[2]Current Patent Assignee: MERCK & CO INC - US2016/333021, 2016, A1 Location in patent: Paragraph 0963

31
[ 172348-63-9 ]
C₃₇H₅₄N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane 1.2: 2 h / 0 °C 2.1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 5 h / 20 °C

Reference： [1]Jecs, Edgars; Miller, Eric J.; Wilson, Robert J.; Nguyen, Huy H.; Tahirovic, Yesim A.; Katzman, Brook M.; Truax, Valarie M.; Kim, Michelle B.; Kuo, Katie M.; Wang, Tao; Sum, Chi S.; Cvijic, Mary E.; Schroeder, Gretchen M.; Wilson, Lawrence J.; Liotta, Dennis C. [ACS Medicinal Chemistry Letters, 2018, vol. 9, # 2, p. 89 - 93]

32
[ 172348-63-9 ]
C₂₇H₃₈N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane 1.2: 2 h / 0 °C 2.1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 5 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

Reference： [1]Jecs, Edgars; Miller, Eric J.; Wilson, Robert J.; Nguyen, Huy H.; Tahirovic, Yesim A.; Katzman, Brook M.; Truax, Valarie M.; Kim, Michelle B.; Kuo, Katie M.; Wang, Tao; Sum, Chi S.; Cvijic, Mary E.; Schroeder, Gretchen M.; Wilson, Lawrence J.; Liotta, Dennis C. [ACS Medicinal Chemistry Letters, 2018, vol. 9, # 2, p. 89 - 93]

33
[ 172348-63-9 ]
[ 1255507-09-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 20 °C / Cooling 1.2: 20 - 60 °C 2.1: hydrogenchloride / 1,4-dioxane / 1.75 h / 20 - 60 °C
	Multi-step reaction with 2 steps 1: rhodium(II) acetate / dichloromethane / 20 °C 2: hydrogenchloride / 1,4-dioxane / 1.75 h / 20 - 60 °C