* 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.
Stage #1: With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at 0℃; for 0.5 h; Stage #2: With ammonium chloride In tetrahydrofuran; water at 0℃; for 0.5 h;
General procedure: To a colorless solution of 150mg (0.50mmol) of Cbz-L-Phe-OH 3a in 10mL of THF were added 67μL (0.70mmol, 1.4equiv) of ClCO2Et and 209μL (1.5mmol, 3.0equiv) of Et3N at 0°C. After stirring for 30min at 0°C, 0.75 ml of a 1.0M aqueous solution of NH4Cl (0.75mmol, 1.5equiv) were added at 0°C to the colorless suspension. The mixture was stirred for 30min at 0°C and 5mL of H2O was added to the resulted mixture. The colorless clear solution was extracted with 30mL of EtOAc and the aqueous layer was extracted with 20mL of EtOAc. The organic layers were combined, washed with 5mL of brine, and dried over anhydrous MgSO4. The crude product was chromatographed on silica gel with EtOAc to afford 129mg (86percent yield) of Cbz-L-Phe-NH2 4a. 4.3.11 Boc-l-Val-NH2 4f 106 mg (98percent); >99percent ee; coloress solid; mp: 149-152 °C; [α]30D = -2.4 (c 1.00, MeOH); 1H NMR (400 MHz, CDCl3): δ 0.94 (d, J = 6.8 Hz, 3H, CH3CH), 0.99 (d, J = 6.8 Hz, 3H, CH3CH), 1.45 (s, 9H, (CH3)3C), 2.16 (ddd, J = 6.7, 6.8, 6.8 Hz, 1H, CH(CH3)2), 3.96 (dd, J = 6.7, 7.8 Hz, 1H, CHCO), 5.03, 5.42, 5.89 (br, br, br, 1H, 1H, 1H, NH, NH2); 13C NMR (100 MHz, CDCl3): δ 17.8, 19.3, 28.3, 30.8, 59.5, 79.9, 156.0, 174.4; IR (KBr, vmax/cm-1): 3386 (CONH), 3345 (CONH), 3205 (CONH), 1680 (CON), 1641 (CON); HRMS (ESI-TOF): Calcd for C10H20N2O3Na (M+Na)+: 239.1366, found: 239.1340; The enantiomeric ratio was determined by HPLC (Chiralcel OD: hexane/2-propanol = 95/5): Tr 9.4 min.
Reference：
[1] Tetrahedron Asymmetry, 2017, vol. 28, # 12, p. 1690 - 1699
[2] Angewandte Chemie - International Edition, 2007, vol. 46, # 25, p. 4771 - 4774
[3] Angewandte Chemie, International Edition, 2009, vol. 48, # 23, p. 4198 - 4201
[4] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 7, p. 2647 - 2648
[5] Tetrahedron, 2009, vol. 65, # 46, p. 9536 - 9541
[6] Organic Letters, 2016, vol. 18, # 11, p. 2560 - 2563
[7] Organic Letters, 2017, vol. 19, # 13, p. 3454 - 3457
[8] Helvetica Chimica Acta, 1963, vol. 46, p. 870 - 889
[9] Journal of Organic Chemistry, 1996, vol. 61, # 23, p. 8207 - 8215
[10] European Journal of Medicinal Chemistry, 1998, vol. 33, # 6, p. 423 - 436
[11] Farmaco, 2000, vol. 55, # 11-12, p. 719 - 724
[12] Heterocycles, 2001, vol. 55, # 5, p. 835 - 840
[13] Tetrahedron Letters, 2007, vol. 48, # 8, p. 1465 - 1468
[14] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 3, p. 591 - 600
[15] Tetrahedron Letters, 1991, vol. 32, # 39, p. 5359 - 5362
[16] Journal of Organic Chemistry, 1973, vol. 38, p. 3565 - 3570
[17] Synthetic Communications, 2009, vol. 39, # 3, p. 395 - 406
[18] Journal of Organic Chemistry, 2009, vol. 74, # 15, p. 5260 - 5266
[19] Journal of Organic Chemistry, 2011, vol. 76, # 23, p. 9845 - 9851
[20] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7355 - 7358
[21] European Journal of Organic Chemistry, 2013, # 36, p. 8154 - 8161
[22] ChemBioChem, 2014, vol. 15, # 1, p. 157 - 169
[23] Journal of Organic Chemistry, 2014, vol. 79, # 9, p. 3895 - 3907
[24] Tetrahedron Letters, 2014, vol. 55, # 50, p. 6831 - 6835
[25] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 4, p. 401 - 406
[26] Amino Acids, 2018, vol. 50, # 11, p. 1595 - 1605
2
[ 128211-52-9 ]
[ 35150-08-4 ]
Yield
Reaction Conditions
Operation in experiment
98%
Stage #1: With 4-methyl-morpholine; isobutyl chloroformate In 1,2-dimethoxyethane at 0℃; for 0.25 h; Inert atmosphere Stage #2: With ammonium hydroxide In 1,2-dimethoxyethane at 0 - 20℃; for 22.5 h; Inert atmosphere
Boc-L-valine (4.00 g, 18.4 mmol, 1.00 equiv) and N-methylmorpholine (2.01 g, 19.9 mmol,1.08 equiv) were dissolved in 1,2-dimethoxyethane (94.0 mL) at 0 °C. Then,isobutylchloroformiate (2.72 g, 19.9 mmol, 1.08 equiv) was added dropwise. The reactionmixture was stirred for 15 min at 0 °C. Afterwards, an aqueous ammonia solution (25percent;8.20 mL, 121 mmol, 6.57 equiv) was added dropwise. The temperature was raised to rt whilestirring. After 22.5 h, the reaction was terminated by adding HCl (1.0 M). The aqueous layerwas extracted with EtOAc (4×). The combined organic layers were washed with HCl (0.1 M)and subsequently dried over MgSO4, filtered and concentrated under reduced pressure.Amide 30 (3.91 g, 18.1 mmol, 98percent) was obtained as a colourless solid.
Reference：
[1] Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 564 - 570
3
[ 24424-99-5 ]
[ 93169-29-0 ]
[ 35150-08-4 ]
Yield
Reaction Conditions
Operation in experiment
85%
With triethylamine In dichloromethane
a Boc-valineamide To a solution of di-t-butyl-dicarbonate (7.15 g, 1 eq) in dry dichloromethane was added valinamide hydrochloride (5.0 g, 1 eq) and triethylamine (9.14 mL, 2 eq). The mixture was heated to reflux for 4 h, and cooled to room temperature. The organic layer was washed twice with water and evaporated to give the title compound (6.03 g, 85percent). NMR(CDCl3) δ 6.00 (1H, br), 5.54 (1H, br), 5.01 (1H, br), 3.93 (1H, dd), 2.12 (1H, m), 1.44 (9H, s), 0.92 (6H, dd).
Reference：
[1] Patent: US5733882, 1998, A,
4
[ 98807-40-0 ]
[ 35150-08-4 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 3, p. 591 - 600
[2] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 15, p. 2455 - 2458
[3] Organic and Biomolecular Chemistry, 2004, vol. 2, # 24, p. 3545 - 3547
[4] Synthesis, 2007, # 22, p. 3535 - 3541
[5] Tetrahedron, 2010, vol. 66, # 34, p. 6718 - 6724
[6] Journal of Organic Chemistry, 2014, vol. 79, # 9, p. 3895 - 3907
[7] Tetrahedron Letters, 2014, vol. 55, # 50, p. 6831 - 6835
5
[ 24424-99-5 ]
[ 3014-80-0 ]
[ 35150-08-4 ]
Reference：
[1] Journal of Organic Chemistry, 1985, vol. 50, # 15, p. 2787 - 2788
[2] Tetrahedron, 1995, vol. 51, # 16, p. 4867 - 4890
General procedure: Compounds 12a-l were afforded by treatment of compounds 11a-l with TFA in dichloromethane, and used directly for next reaction without further purified.
With pyridine; trifluoroacetic anhydride; In tetrahydrofuran; at 0℃; for 3h;
General procedure: To a solution of Nalpha-protected amino acid (10 mmol) in THF (10 mL), NMM(11 mmol) and ethyl chloroformate (11 mmol) were added at -15 C followed by stirring for 20 min NH3 solution (0.4 mL) was added and stirring was continued for another 4 h. After completion of the reaction (TLC), the solvent was removed in vacuo andthe residue was dissolved in EtOAc (30 mL), washed twice with 10% HCl (10 mL)(in case of Fmoc, Z-amino acids), or 10% citric acid (10 mL) (in case of Boc-amino acids), brine solution (10 mL) and dried over anhydrous Na2SO4. After evaporation of the solvent, the crude product was purified by recryastallization from EtOAc:hexane (3:8). The solution of amino acid amide (10mmol) in dry THF (10 mL) was treated with pyridine (20 mmol) and TFAA (12 mmol)and the reaction mixture was stirred at 0 C for 3 h. After completion of the reaction (TLC), the solvent was evaporated and residue wasdissolved in EtOAc (30 mL), washed twice with 10% HCl (10 mL) (in case of Fmoc,Z-amino acids), or 10% citric acid (10 mL) (in case of Boc-amino acids), saturatedNaHCO3 (10 mL), brine solution (10 mL) and dried over anhydrous Na2SO4. The solvent was removed in vacuo and the residue was purified by column chromatography (hexane:EtOAc 9:1).
(S)-ethyl 2'-[1-(tert-butoxycarbonylamino)-2-methylpropyl]-5'-methyl-5-[1-(2-nitrobenzenesulfonyl)-1H-indol-3-yl][2,4']bisoxazolyl-4-carboxylate[ No CAS ]
ethyl 3-[2-(1-tert-butoxycarbonylamino-2(S)-methylpropyl)-5-methyloxazole-4-carbonyl]amino}-2-[1-(2-nitrobenzenesulfonyl)-1H-indol-3-yl]-3-oxopropionate[ No CAS ]
2-Phenyl-thiazole-4-carboxylic acid ((1S,2R)-2-hydroxy-1-{(S)-2-methyl-1-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-propylcarbamoyl}-propyl)-amide[ No CAS ]
2-Phenyl-thiazole-4-carboxylic acid ((1S,2R)-2-hydroxy-1-{(S)-1-[4-(4-hydroxy-piperidine-1-carbonyl)-thiazol-2-yl]-2-methyl-propylcarbamoyl}-propyl)-amide[ No CAS ]
2-Phenyl-thiazole-4-carboxylic acid ((1S,2R)-2-hydroxy-1-{(S)-1-[4-(4-hydroxymethyl-piperidine-1-carbonyl)-thiazol-2-yl]-2-methyl-propylcarbamoyl}-propyl)-amide[ No CAS ]
2-Phenyl-thiazole-4-carboxylic acid [(1S,2R)-2-hydroxy-1-((S)-1-{4-[4-(2-hydroxy-ethyl)-piperidine-1-carbonyl]-thiazol-2-yl}-2-methyl-propylcarbamoyl)-propyl]-amide[ No CAS ]
2-Phenyl-thiazole-4-carboxylic acid ((1S,2R)-2-hydroxy-1-{(S)-2-methyl-1-[4-(4-pyridin-2-yl-piperazine-1-carbonyl)-thiazol-2-yl]-propylcarbamoyl}-propyl)-amide[ No CAS ]
2-Phenyl-thiazole-4-carboxylic acid ((1S,2R)-2-hydroxy-1-{(S)-2-methyl-1-[4-(4-pyridin-4-yl-piperazine-1-carbonyl)-thiazol-2-yl]-propylcarbamoyl}-propyl)-amide[ No CAS ]
2-Phenyl-thiazole-4-carboxylic acid {(1S,2R)-2-hydroxy-1-[(S)-1-(4-{4-[2-(2-hydroxy-ethoxy)-ethyl]-piperidine-1-carbonyl}-thiazol-2-yl)-2-methyl-propylcarbamoyl]-propyl}-amide[ No CAS ]
A solution of 12001a (2.0 g, 9.2 mmol, Indofine chemicals) in toluene (150 mL) was treated with BH3DMS (-10 M, 3 mL) and heated at 90 C for 2 h. The reaction mixture was cooled to 0 C and diluted with 2 M aq. NaOH. The organic layer was extracted with CH2CI2 and the combined organic layers were dried (MgS04) filtered concentrated in vacuo to yield 1.1 g of 12001b.
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