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Product Details of [ 56-41-7 ]

CAS No. :56-41-7 MDL No. :MFCD00064410
Formula : C3H7NO2 Boiling Point : -
Linear Structure Formula :CH3(NH2)CHCOOH InChI Key :QNAYBMKLOCPYGJ-REOHCLBHSA-N
M.W : 89.09 Pubchem ID :5950
Synonyms :
Alanine;2-Aminopropanoic Acid;NSC 206315;(2S)-2-Azaniumylpropanoate;(S)-Alanine;L-(+)-Alanine;α-Alanine

Calculated chemistry of [ 56-41-7 ]

Physicochemical Properties

Num. heavy atoms : 6
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.67
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 2.0
Molar Refractivity : 21.01
TPSA : 63.32 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.95 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.34
Log Po/w (XLOGP3) : -2.96
Log Po/w (WLOGP) : -0.58
Log Po/w (MLOGP) : -3.06
Log Po/w (SILICOS-IT) : -1.04
Consensus Log Po/w : -1.46

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 3.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : 1.54
Solubility : 3080.0 mg/ml ; 34.5 mol/l
Class : Highly soluble
Log S (Ali) : 2.19
Solubility : 13800.0 mg/ml ; 155.0 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : 0.77
Solubility : 523.0 mg/ml ; 5.87 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 56-41-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 56-41-7 ]

* 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 [ 56-41-7 ]
  • Downstream synthetic route of [ 56-41-7 ]

[ 56-41-7 ] Synthesis Path-Upstream   1~74

  • 1
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YieldReaction ConditionsOperation in experiment
79.3% With sodium carbonate In water at 20℃; for 1.5 h; To a stirred solution of 2 in H2O (100 mL) were added L-alanine(8.9 g, 100.00 mmol) and Na2CO3 (10.6 g, 100.00 mmol). After1.5 h, the aqueous solution was slowly acidified with aqueousHCl (1 N) until pH = 1–2, and filtered to obtain 17.37 g (79.3percent yield)as white solid. Mp 145.8–146.6 C. 1H NMR (CDCl3, 400 MHz) d1.71 (s, 3H, CH3), 5.02 (q, J = 7.4 Hz, 1H, CH), 7.69–7.75 (m, 2H,Ar-H), 7.82–7.88 (m, 2H, Ar-H). MS (ESI): m/z 218.2 [MH].
79.3% With sodium carbonate In water for 2 h; II-1 the compound (21.9g, 100mmol) and L-alanine (8.9g, 100mmol) dissolved in H2O (100 ml) in, adding Na2CO3(10.6g, 100mmol), TLC detection reaction, 2h end of the reaction, adding 1NHCl adjusting PH value to 2, filter, vacuum drying to obtain pure (type II-2) compound 17.4g, yield 79.3percent
Reference: [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 51, p. 13588 - 13592[2] Angew. Chem., 2013, vol. 125, # 51, p. 13833 - 13837,5
[3] Chemical Communications, 2017, vol. 53, # 47, p. 6351 - 6354
[4] Synthetic Communications, 1983, vol. 13, # 4, p. 311 - 318
[5] Synthetic Communications, 1983, vol. 13, # 5, p. 393 - 402
[6] Agricultural and Biological Chemistry, 1985, vol. 49, # 4, p. 973 - 980
[7] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 11, p. 2576 - 2588
[8] Patent: CN105732683, 2016, A, . Location in patent: Paragraph 0090; 0091; 0094; 0095
[9] Organic Letters, 2012, vol. 14, # 21, p. 5518 - 5521,4
[10] Journal of the American Chemical Society, 2015, vol. 137, # 14, p. 4618 - 4621
[11] Patent: WO2015/131100, 2015, A1, . Location in patent: Page/Page column 157; 158
[12] Organic and Biomolecular Chemistry, 2018, vol. 16, # 37, p. 6933 - 6939
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YieldReaction ConditionsOperation in experiment
94% at 170℃; for 2.5 h; General procedure: The synthesis of 2-imidoalkanecarboxylic acids 6 wascarried out based on the modified procedure described byMcKenzie and Walker [32]. The corresponding α-amino acid(10 mmol) was heated with phthalic or succinic anhydride(11 mmol) at 170 °C or 140 °C under reduced pressure for thetime given in Table 1. The crude product was recrystallizedfrom toluene.
90.3% for 24 h; Reflux Example 14Preparation of (1R, 2S)-1-phenyl-2-(4-(2-methoxyphenyl)piperazinyl)propan-1-ol (II-1) hydrochloride and (1S, 2S)-1-phenyl-2-(4-(2-methoxyphenyl)piperazinyl)propan-1-ol (II-2) hydrochloride1) Preparation of (S)-2-(1,3-dicarbonyl isoindole) propionic acid(S)-2-amino propionic acid (4.45 g, 0.05 mol), phthalic anhydride (7.40 g, 0.05 mol) and triethylamine (0.8 ml) were added to 150 ml of toluene, and heated till refluxing. A reaction was allowed to proceed for 24 hours. The reaction mixture was cooled, evaporated to remove the solvent, added to 50 ml of water, and extracted with ethyl acetate (3.x.50 ml). The ethyl acetate layer was washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and evaporated to remove the solvent, thereby obtaining 9.9 g of white solid. The yield was 90.3percent.MS: m/z 219.1.
82% With triethylamine In toluene for 10 h; Reflux; Dean-Stark The brown residue obtained from the above procedure was mixed with 105 phthalic anhydride (5.5 mmol), 106 triethylamine (5.5 mmol) and 13 toluene (50 mL). The mixture was refluxed overnight in a round bottom flask equipped with a Dean-Stark trap. The reaction was cooled to r.t. and the mixture was concentrated in vacuum to give the crude product, which was then dissolved in 107 dichloromethane (DCM). To the 108 DCM solution was added a 109 concentrated aqueous HCl solution (37percent, 1 mL). The mixture was washed with water and the organic layer was dried over Na2SO4. The solvent was removed under vacuum and the resulting 74 solid was recrystallized from DCM/pentane (2/1 to 1/2 in v/v), resulting the N-Phth protected product in 82percent yield.
70% at 160℃; for 1.5 h; General procedure: The (S)-amino acids 1a–c and 1e (1mmol, 1equiv) and phthalic anhydride (1.5mmol, 1.5equiv) were heated together at 130–160°C. After completion of the reaction, the unreacted phthalic anhydride was scraped off from the walls of the flask and the crude acid that remained in the flask was purified by crystallization, from different solvents, to afford pure crystals of 3a–c, e (Table 4). 4.1.1
(2S)-2-(1,3-Dioxo-2-benzazole-2-yl)propanoic acid 3a
Colourless prisms (2.5 g, 70percent), mp 160 °C, Rf: 0.28 (EtOAc); [α]D29 = -32.0 (c 1.5, EtOAc); νmax (cm-1): 1720 (C=O); log ε (λmax, nm): 3.2003 (295.5); δH (400 MHz, CD3OD, in ppm): 1.65 (3H, d, J = 7.2 Hz, H3), 4.94 (1H, q, J = 7.2 Hz, H2) and 7.80-7.90 (4H, m, aromatic Hs); LR EIMS m/z in amu (percent abundance): 219 (21) [M]+⩽, 175 (86) [M-CO2]+⩽ and 174 (100) [M-OH-CO]+.

Reference: [1] Organic Letters, 2004, vol. 6, # 21, p. 3675 - 3678
[2] Chemische Berichte, 1992, vol. 125, # 11, p. 2467 - 2476
[3] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1446 - 1455
[4] Carbohydrate Research, 2006, vol. 341, # 17, p. 2858 - 2866
[5] Journal of Organic Chemistry, 1993, vol. 58, # 21, p. 5732 - 5737
[6] Patent: US2011/294822, 2011, A1, . Location in patent: Page/Page column 17
[7] Chemistry and Biodiversity, 2010, vol. 7, # 11, p. 2718 - 2726
[8] Patent: US2017/283447, 2017, A1, . Location in patent: Paragraph 0328
[9] Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 12, p. 2863 - 2875
[10] Phosphorus, Sulfur and Silicon and the Related Elements, 2010, vol. 185, # 7, p. 1526 - 1535
[11] Angewandte Chemie - International Edition, 2012, vol. 51, # 21, p. 5188 - 5191
[12] Medicinal Chemistry Research, 2014, vol. 23, # 4, p. 1701 - 1708
[13] Tetrahedron Asymmetry, 2014, vol. 25, # 9, p. 736 - 743
[14] Chirality, 2015, vol. 27, # 12, p. 951 - 957
[15] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 3, p. 1079 - 1083
[16] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 5, p. 475 - 483
[17] Journal of the Chemical Society, 1955, p. 900,903
[18] Journal of Organic Chemistry, 1958, vol. 23, p. 1335,1337
[19] Org.Synth.Coll.Vol.V <1973> 973,
[20] Chemische Berichte, 1990, vol. 123, # 8, p. 1691 - 1698
[21] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 2201 - 2208
[22] Agricultural and Biological Chemistry, 1991, vol. 55, # 10, p. 2669 - 2672
[23] Journal of Organic Chemistry, 1997, vol. 62, # 13, p. 4293 - 4301
[24] Journal of Organic Chemistry, 1980, vol. 45, # 11, p. 2145 - 2151
[25] Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 9, p. 2728 - 2730
[26] Journal of the American Chemical Society, 2000, vol. 122, # 42, p. 10452 - 10453
[27] Organic and Biomolecular Chemistry, 2003, vol. 1, # 6, p. 965 - 972
[28] Letters in Organic Chemistry, 2010, vol. 7, # 1, p. 69 - 72
[29] Organic and Biomolecular Chemistry, 2013, vol. 11, # 33, p. 5491 - 5499
[30] Arkivoc, 2012, vol. 2012, # 3, p. 149 - 171
[31] Angewandte Chemie - International Edition, 2013, vol. 52, # 42, p. 11124 - 11128[32] Angew. Chem., 2013, vol. 125, # 42, p. 11330 - 11334,5
[33] Advanced Synthesis and Catalysis, 2014, vol. 356, # 2-3, p. 596 - 602
[34] MedChemComm, 2014, vol. 5, # 6, p. 758 - 765
[35] Chemistry - A European Journal, 2015, vol. 21, # 20, p. 7389 - 7393
[36] RSC Advances, 2015, vol. 5, # 40, p. 31759 - 31767
[37] Organic and Biomolecular Chemistry, 2015, vol. 13, # 19, p. 5444 - 5449
[38] Synthesis (Germany), 2015, vol. 47, # 11, p. 1669 - 1677
[39] Green Chemistry, 2015, vol. 17, # 7, p. 4016 - 4028
[40] RSC Advances, 2015, vol. 5, # 61, p. 49132 - 49142
[41] Patent: WO2015/131100, 2015, A1, . Location in patent: Page/Page column 80-85
[42] Synthesis (Germany), 2016, vol. 48, # 3, p. 448 - 454
[43] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 14, p. 3237 - 3242
[44] Tetrahedron, 2016, vol. 72, # 40, p. 6031 - 6036
[45] Chemistry - An Asian Journal, 2018, vol. 13, # 5, p. 496 - 499
[46] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 13, p. 3837 - 3844
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Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 574 - 577
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  • [ 56-87-1 ]
  • [ 131543-46-9 ]
  • [ 290-37-9 ]
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  • [ 13925-00-3 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 4, p. 2470 - 2478
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  • [ 56-87-1 ]
  • [ 131543-46-9 ]
  • [ 290-37-9 ]
  • [ 13925-00-3 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 18, p. 4697 - 4708
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  • [ 56-87-1 ]
  • [ 290-37-9 ]
  • [ 5910-89-4 ]
  • [ 13925-00-3 ]
  • [ 13360-65-1 ]
  • [ 13925-03-6 ]
  • [ 13925-07-0 ]
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  • [ 13360-64-0 ]
  • [ 15707-34-3 ]
  • [ 18138-04-0 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 18, p. 4697 - 4708
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Reference: [1] Organic Letters, 2016, vol. 18, # 15, p. 3738 - 3741
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  • [ 109-77-3 ]
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YieldReaction ConditionsOperation in experiment
66%
Stage #1: at 50℃; for 12 h;
Stage #2: With sodium hydroxide In water at 60℃;
A mixture of Ac2O (16.9 g, 165 mmol), AcOH (2.26 g,37.6 mmol), Et3N (19.0 g, 188 mmol), and 4-dimethylaminopyridine (0.10 g, 0.75 mmol) was heated to 50°C. L-Alanyl acid (6.79 g, 76.2 mmol) was added in small portions over 4 h, and the resulting red reaction mixture was stirred for 8 h at 50°C; then the residual Ac2O, AcOH, and Et3N were removed under reduced pressure at 100°C. Water (40 mL) and malononitrile (4.71 g, 71.3 mmol) were added to the residue, and the mixture was slowly poured into a 30percent NaOH solution (25 mL) at a temperature below 60°C. The reaction solution was cooled to 0°C, and the precipitated orange solid was washed with water (45 mL) and dried under vacuum to give a beige solid product (6.65 g, 66percent). 1H NMR(400 MHz, DMSO-d6), δ (ppm): 1.83 (s, 3H), 1.92 (s, 3H),5.32 (s, 2H), 9.80 (s, 1H). ESI-MS, m/z calcd. for C7H9N3Na.158.2, found [M + Na ]+ 158.2.
Reference: [1] Bulletin of the Korean Chemical Society, 2015, vol. 36, # 4, p. 1143 - 1147
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Reference: [1] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 4, p. 2470 - 2478
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  • [ 13925-07-0 ]
  • [ 13925-08-1 ]
  • [ 13360-64-0 ]
  • [ 15707-34-3 ]
  • [ 18138-04-0 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 18, p. 4697 - 4708
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Reference: [1] Journal of Medicinal Chemistry, 2009, vol. 52, # 2, p. 389 - 396
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YieldReaction ConditionsOperation in experiment
64%
Stage #1: at 60℃; for 3 h;
Stage #2: With dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 0 - 22℃; for 18.5 h;
To a solution of maleic anhydride (8; 86.0 g, 877 mmol) in DMF(1.03 L) was added β-alanine (9; 78.14 g, 877 mmol). The resultingsuspension was heated to 60 °C and, after 1 h, a solution was obtained.After 2 h, the mixture was cooled to 0–5 °C and N-hydroxysuccinimide(29; 126.17 g, 1.09 mol) was added followed by DCC(361.9 g, 1.75 mol) over 30 min in several portions while the internaltemperature was held below 22 °C. The thick, white slurry wasthen stirred at 20 °C for 18 h. The slurry was filtered and the solid(dicyclohexyl urea) was washed with H2O (1 L) and CH2Cl2 (1 L)and discarded. To the filtrates was added CH2Cl2 (1 L) and the phaseswere separated. The aqueous layer was extracted with CH2Cl2(2 × 300 mL) and the combined organic extracts were washed withH2O [500 mL; a small amount of brine (50 mL) was added to facilitatephase separation], sat. aq NaHCO3 (2 × 300 mL), and dried(MgSO4). The solvent was removed to give an oily, light tan solidthat was slurried in EtOH (520 mL) for 2 h at 20 °C. The solid wasfiltered, washed with EtOH (2 × 75 mL) and dried under vacuum at30 °C for 72 h to give 186.35 g (64percent) of NHS ester 30 as a whitesolid;32 HPLC purity: 96.6percent (areapercent); mp 169–171 °C.IR (ATR cell): 3088, 2954, 1825, 1783, 1705, 1583, 1446, 1433,1382, 1325, 1298, 1250, 1211, 1149, 1070, 1049, 998, 956, 901,836, 813, 786, 767, 756, 696, 651, 634, 596, 561, 544, 528 cm–1.1H NMR (400 MHz, DMSO-d6): δ = 2.80 (s, 4 H), 3.05 (t, J = 6.90Hz, 2 H), 3.75 (t, J = 6.78 Hz, 2 H), 7.05 (s, 2 H).13C NMR (100 MHz, DMSO-d6): δ = 25.38, 29.00, 32.67, 134.63,166.72, 169.93, 170.52.HRMS (ESI): m/z [M + H]+ calcd for C11H11N2O6: 267.06116;found: 267.06147.
Reference: [1] Synthesis (Germany), 2014, vol. 46, # 10, p. 1399 - 1406
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  • [ 108-31-6 ]
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  • [ 7423-55-4 ]
Reference: [1] Synthesis (Germany), 2014, vol. 46, # 10, p. 1399 - 1406
  • 14
  • [ 87-72-9 ]
  • [ 56-41-7 ]
  • [ 3658-77-3 ]
  • [ 27538-10-9 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 1996, vol. 44, # 2, p. 531 - 536
  • 15
  • [ 58-86-6 ]
  • [ 56-41-7 ]
  • [ 3658-77-3 ]
  • [ 27538-10-9 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2003, vol. 51, # 9, p. 2708 - 2713
  • 16
  • [ 87-72-9 ]
  • [ 56-41-7 ]
  • [ 27538-10-9 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 1996, vol. 44, # 2, p. 531 - 536
  • 17
  • [ 56-41-7 ]
  • [ 109-06-8 ]
  • [ 302-17-0 ]
  • [ 5625-46-7 ]
Reference: [1] Journal of Agricultural and Food Chemistry, 2014, vol. 62, # 33, p. 8518 - 8523
  • 18
  • [ 56-41-7 ]
  • [ 2749-11-3 ]
  • [ 35320-23-1 ]
Reference: [1] Organic Letters, 2003, vol. 5, # 4, p. 527 - 530
  • 19
  • [ 1116-19-4 ]
  • [ 56-41-7 ]
  • [ 338-69-2 ]
  • [ 2013-12-9 ]
  • [ 6600-40-4 ]
Reference: [1] Tetrahedron, 1980, vol. 36, # 81, p. 1089 - 1098
[2] Tetrahedron, 1980, vol. 36, # 81, p. 1089 - 1098
[3] Tetrahedron, 1980, vol. 36, # 81, p. 1089 - 1098
[4] Tetrahedron, 1980, vol. 36, # 81, p. 1089 - 1098
  • 20
  • [ 56-41-7 ]
  • [ 2885-02-1 ]
Reference: [1] Journal of the American Chemical Society, 1952, vol. 74, p. 1096
  • 21
  • [ 56-41-7 ]
  • [ 71-36-3 ]
  • [ 2885-02-1 ]
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 8, p. 2829 - 2838
  • 22
  • [ 1187486-24-3 ]
  • [ 56-41-7 ]
  • [ 3913-67-5 ]
  • [ 2480-23-1 ]
  • [ 2812-28-4 ]
  • [ 56564-52-4 ]
Reference: [1] Journal of Natural Products, 2009, vol. 72, # 9, p. 1573 - 1578
  • 23
  • [ 1268813-03-1 ]
  • [ 56-41-7 ]
  • [ 2812-28-4 ]
  • [ 80999-51-5 ]
  • [ 86118-11-8 ]
  • [ 87421-24-7 ]
Reference: [1] Journal of Natural Products, 2011, vol. 74, # 2, p. 185 - 193
  • 24
  • [ 1268813-04-2 ]
  • [ 56-41-7 ]
  • [ 2812-28-4 ]
  • [ 80999-51-5 ]
  • [ 86118-11-8 ]
  • [ 87421-24-7 ]
Reference: [1] Journal of Natural Products, 2011, vol. 74, # 2, p. 185 - 193
  • 25
  • [ 1268813-06-4 ]
  • [ 56-41-7 ]
  • [ 2812-28-4 ]
  • [ 80999-51-5 ]
  • [ 86118-11-8 ]
  • [ 87421-24-7 ]
Reference: [1] Journal of Natural Products, 2011, vol. 74, # 2, p. 185 - 193
  • 26
  • [ 1268813-05-3 ]
  • [ 56-41-7 ]
  • [ 2812-28-4 ]
  • [ 80999-51-5 ]
  • [ 86118-11-8 ]
  • [ 87421-24-7 ]
Reference: [1] Journal of Natural Products, 2011, vol. 74, # 2, p. 185 - 193
  • 27
  • [ 1115-69-1 ]
  • [ 56-41-7 ]
  • [ 19436-52-3 ]
Reference: [1] Journal of the American Chemical Society, 1989, vol. 111, # 16, p. 6354 - 6364
  • 28
  • [ 56-41-7 ]
  • [ 77287-34-4 ]
  • [ 56-45-1 ]
  • [ 70-47-3 ]
  • [ 471-46-5 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 2014, vol. 87, # 11, p. 1208 - 1215
  • 29
  • [ 56-41-7 ]
  • [ 77287-34-4 ]
  • [ 56-45-1 ]
  • [ 70-47-3 ]
  • [ 56-40-6 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 2014, vol. 87, # 11, p. 1208 - 1215
  • 30
  • [ 56-41-7 ]
  • [ 79-08-3 ]
  • [ 56857-47-7 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1980, vol. 53, # 9, p. 2555 - 2565
  • 31
  • [ 56-41-7 ]
  • [ 79-11-8 ]
  • [ 56857-47-7 ]
Reference: [1] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 202, p. 54
[2] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 202, p. 54
[3] Tetrahedron, 1975, vol. 31, # 9, p. 1135 - 1137
  • 32
  • [ 1207162-72-8 ]
  • [ 56-41-7 ]
  • [ 72-18-4 ]
  • [ 72-19-5 ]
  • [ 3226-65-1 ]
  • [ 6893-26-1 ]
  • [ 556-02-5 ]
Reference: [1] Phytochemistry, 2009, vol. 70, # 17-18, p. 2058 - 2063
  • 33
  • [ 77935-68-3 ]
  • [ 56-41-7 ]
  • [ 56-85-9 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1980, vol. 28, # 12, p. 3549 - 3554
  • 34
  • [ 17351-39-2 ]
  • [ 56-41-7 ]
  • [ 65-82-7 ]
Reference: [1] Chemistry Letters, 1998, # 11, p. 1079 - 1080
[2] Dalton Transactions, 2005, # 9, p. 1613 - 1619
  • 35
  • [ 56-41-7 ]
  • [ 144-62-7 ]
  • [ 71-36-3 ]
  • [ 2050-60-4 ]
  • [ 1246345-80-1 ]
Reference: [1] Organic Process Research and Development, 2013, vol. 17, # 12, p. 1498 - 1502
  • 36
  • [ 56-41-7 ]
  • [ 1280225-71-9 ]
  • [ 27317-69-7 ]
YieldReaction ConditionsOperation in experiment
74%
Stage #1: With sodium carbonate In water at 20℃;
Stage #2: at 20℃; for 10.0833 h;
Stage #3: With potassium hydrogensulfate In tetrahydrofuran; water
General procedure: At first, l-alanine 0.45 g (0.00516 mol) and Na2CO3 1.64 g (0.01548 mol) were dissolved in 16 ml of water at room temperature in a 100 ml three necked round bottomed flask. Boc-l-alanine-ASUD ester 1.9 g (0.00516 mol) dissolved in 16 ml of THF was added to the above reaction mixture at room temperature over a period of 5 min. After the addition was complete, the reaction mixture was stirred for 10 h at room temperature. The reaction mixture was acidified with 5percent KHSO4 to reach a pH of 2-3.The product was extracted into ethyl acetate. The ethyl acetate extract was washed with 5percent Na2CO3 solution, water, brine solution and dried over anhydrous Na2SO4. The ethyl acetate was removed at reduced pressure. The oily crude product obtained was crystallized using ethyl acetate and n-hexane. The yield of white crystalline Boc-l-Ala-Ala-OH is 0.98 g (74percent).
Reference: [1] Tetrahedron Asymmetry, 2011, vol. 22, # 1, p. 22 - 25
  • 37
  • [ 73488-76-3 ]
  • [ 56-41-7 ]
  • [ 27317-69-7 ]
YieldReaction ConditionsOperation in experiment
76.3% With NMM In N-benzyl-trimethylammonium hydroxide; acetic acid; N,N-dimethyl-formamide; Petroleum ether EXAMPLE 23
Boc-Ala-Ala-OH
L-Alanine (3.57 g, 40 mmol) was dissolved in 18.8 ml of Triton B (40 mmol), evaporated to dryness, and the oily residue re-evaporated twice with DMF (30 ml each).
The salt obtained was stirred with 11.45 g of Boc-Ala-OSu (40 mmol) in 40 ml DMF, with 4 ml of NMM added, for 20 hours.
The solvent was removed and the residue taken up in 10percent HOAc (100 ml).
The product was extracted into EtOAc (4 times 100 ml), washed twice with a small volume of H2 O, dried over Na2 SO4, evaporated to a small volume, and treated with petroleum ether until cloudiness developed.
A crystalline product formed on storage in the refrigerator overnight: Yield, 8.2 g (76.3percent); mp 115°-118°.
Anal. Calcd for C11 H20 N2 O5.1/2H2 O (269.30): C, 49.05; H, 7.86; N, 10.39. Found: C, 48.90; H, 7.93; N, 10.15.
76.3% With NMM In N-benzyl-trimethylammonium hydroxide; acetic acid; N,N-dimethyl-formamide; Petroleum ether EXAMPLE 23
Boc-Ala-Ala-OH.
L-Alanine (3.57 g, 40 mmol) was dissolved in 18.8 ml of Triton B (40 mmol), evaporated to dryness, and the oily residue re-evaporated twice with DMF (30 ml each).
The salt obtained was stirred with 11.45 g of Boc-Ala-OSu (40 mmol) in 40 ml DMF, with 4 ml of NMM added, for 20 hours.
The solvent was removed and the residue taken up in 10percent HOAc (100 ml).
The product was extracted into EtOAc (4 times 100 ml), washed twice with a small volume of H2 O, dried over Na2 SO4, evaporated to a small volume, and treated with petroleum ether until cloudiness developed.
A crystalline product formed on storage in the refrigerator overnight: Yield, 8.2 g (76.3percent); mp 115°-118°.
Anal. Calcd for C11 H20 N2 O5.1/2 H2 O (269.30): C, 49.05; H, 7.86; N, 10.39. Found: C, 48.90; H, 7.93; N, 10.15.
Reference: [1] Patent: US4148788, 1979, A,
[2] Patent: US4116951, 1978, A,
  • 38
  • [ 56-41-7 ]
  • [ 2483-49-0 ]
  • [ 27317-69-7 ]
Reference: [1] Synlett, 2011, # 10, p. 1427 - 1430
  • 39
  • [ 56-41-7 ]
  • [ 27317-69-7 ]
Reference: [1] Russian Journal of Bioorganic Chemistry, 1995, vol. 21, # 9, p. 590 - 595[2] Bioorganicheskaya Khimiya, 1995, vol. 21, # 9, p. 684 - 690
  • 40
  • [ 83904-90-9 ]
  • [ 56-41-7 ]
  • [ 27317-69-7 ]
Reference: [1] Synlett, 2011, # 10, p. 1427 - 1430
  • 41
  • [ 51806-98-5 ]
  • [ 56-41-7 ]
  • [ 35320-22-0 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1995, vol. 132, p. 119 - 127
[2] Bulletin de la Societe Chimique de France, 1995, vol. 132, p. 119 - 127
  • 42
  • [ 50-00-0 ]
  • [ 56-41-7 ]
  • [ 2812-31-9 ]
YieldReaction ConditionsOperation in experiment
4.4 g With hydrogenchloride; palladium 10% on activated carbon; hydrogen In methanol; water for 5 h; A mixture of L-alanine (2.5 g, 28 mmol), formaldehyde (8.4 g, 37 wt. percent), 1N HCl (30 mL) and 10percent Pd/C (500mg) in methanol (30 mL) was stirred under a hydrogen atmosphere (50 psi) for 5 hours. The reaction mixture was filteredthrough diatomaceous earth (Celite®) and the filtrate was concentrated in vacuo to provide the HCl salt of Cap-13 asan oil which solidified upon standing under vacuum (4.4 g; the mass is above theoretical yield). The product was usedwithout further purification. 1H NMR (DMSO-d6, δ=2.5, 500 MHz) δ 12.1 (br s, 1H), 4.06 (q, J=7.4, 1H), 2.76 (s, 6H), 1.46(d, J=7.3, 3H).
Reference: [1] Tetrahedron Asymmetry, 2011, vol. 22, # 4, p. 464 - 467
[2] Organic Letters, 2013, vol. 15, # 12, p. 3118 - 3121
[3] Tetrahedron Letters, 2007, vol. 48, # 43, p. 7680 - 7682
[4] Synthesis, 2011, # 3, p. 490 - 496
[5] Bulletin of the Chemical Society of Japan, 1968, vol. 41, # 7, p. 1679 - 1681
[6] Tetrahedron Letters, 1980, vol. 21, # 1, p. 79 - 82
[7] Australian Journal of Chemistry, 1991, vol. 44, # 11, p. 1591 - 1601
[8] Analytical Chemistry, 2007, vol. 79, # 22, p. 8631 - 8638
[9] Patent: WO2010/17401, 2010, A1, . Location in patent: Page/Page column 194
[10] Journal of Mass Spectrometry, 2015, vol. 50, # 5, p. 771 - 781
[11] Phytochemistry, 2015, vol. 119, p. 90 - 95
[12] Patent: EP2328865, 2017, B1, . Location in patent: Paragraph 0362-0363
[13] Patent: US2008/44379, 2008, A1, . Location in patent: Page/Page column 37-38
  • 43
  • [ 56-41-7 ]
  • [ 2812-31-9 ]
Reference: [1] The Journal of pharmacy and pharmacology, 1963, vol. 15, p. 349 - 361
  • 44
  • [ 56-41-7 ]
  • [ 67-63-0 ]
  • [ 39825-33-7 ]
YieldReaction ConditionsOperation in experiment
87% at 0 - 20℃; SOCl2 (29 mL, 400 mmcl) was added dropwise at 0 °C to a suspension of the HCl salt of L-alanine (17.8 g, 200 mmcl) in isopropanol (700 mL). The suspension was stirred at roomtemperature over night, then concentrated, which gave the title compound (29.2 g, 87percent).
74% at 120℃; for 0.333333 h; Microwave irradiation General procedure: In a typical reaction, AMA 2:3 (498 g, 1 mol), the corresponding aminoacid(1 mol) and alcohol (1.5–2 mol) were mixed in the provided reaction glass tubeequipped with a screw cap and magnetic agitation until a wet mixture was achieved.The reaction mixture was irradiated with microwaves (Anton Parr Monowave 300reactor) at 120 C for 20 min. On cooling, the mixture was diluted with chloroform(41 mL), filtered with glass frit over celite under vacuum, and washed with chloroform;then the filtrate was washed with Na2CO3 (ss) and water. The organic layerwas dried over Na2SO4, filtered, and concentrated under reduced pressure to givethe ester.
69% for 12 h; Reflux General procedure: Synthesis of L-amino acid isopropyl esters
Concentrated sulfuric acid was added to a suspension of the respective L-amino acid (1 g, amino acid:sulfuric acid ratio 1:1.2) in isopropanol (10 mL).
The resulting solution was refluxed for 12 h.
After this time, the solution was cooled to 0 °C and neutralized with concentrated NH4OH.
The ammonium sulfate formed was filtered and washed with isopropanol (3 * 5 mL).
The filtrate was concentrated under reduced pressure (50 mm Hg, 50 °C) to a third of its volume.
The ester was extracted with chloroform (3 * 5 mL), the organic phase was dried with anhydrous sodium sulfate, and chloroform was removed under reduced pressure (50 mm Hg, room temperature).
L-Alanine isopropyl ester (C6H13NO2·HOC3H7) b.p.125-127 °C , yield 69percent. 1H NMR (CDCl3) δ: 1.27 (d,6H, J = 6.8 Hz), 1.29 (d,6H, J = 6.4 Hz), 1.61 (d,3H, J = 7.2 Hz), 4.11 (q,1H, J = 7.2 Hz), 4.62 (heptet,1H, J = 6.4 Hz), 5.10 (heptet,1H, J = 6.4 Hz), ESI-MS: m/z 131.90 [M + H]+.
Reference: [1] Patent: WO2015/56213, 2015, A1, . Location in patent: Page/Page column 66
[2] Synthetic Communications, 2014, vol. 44, # 16, p. 2386 - 2392
[3] Journal of Molecular Structure, 2013, vol. 1041, p. 68 - 72
[4] Analytical Chemistry, 1991, vol. 63, # 4, p. 370 - 374
[5] Analytical Chemistry, 1997, vol. 69, # 5, p. 926 - 929
[6] Nucleosides, Nucleotides and Nucleic Acids, 2001, vol. 20, # 4-7, p. 621 - 628
[7] Patent: WO2015/40640, 2015, A2, . Location in patent: Page/Page column 18
  • 45
  • [ 56-41-7 ]
  • [ 910902-20-4 ]
  • [ 2817-13-2 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1965, vol. 682, p. 244 - 249
  • 46
  • [ 56-41-7 ]
  • [ 102156-97-8 ]
  • [ 2817-13-2 ]
Reference: [1] Chemische Berichte, 1960, vol. 93, p. 2983 - 3005
  • 47
  • [ 7797-39-9 ]
  • [ 56-41-7 ]
  • [ 2817-13-2 ]
Reference: [1] Chemische Berichte, 1966, vol. 99, p. 2944 - 2954
  • 48
  • [ 56-41-7 ]
  • [ 26582-86-5 ]
  • [ 24787-87-9 ]
Reference: [1] Journal of Medicinal Chemistry, 1977, vol. 20, # 5, p. 648 - 655
  • 49
  • [ 56-41-7 ]
  • [ 100-52-7 ]
  • [ 6940-80-3 ]
Reference: [1] Liebigs Annalen der Chemie, 1994, # 2, p. 121 - 128
  • 50
  • [ 1446522-56-0 ]
  • [ 56-41-7 ]
  • [ 825-22-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4670 - 4677
  • 51
  • [ 540-88-5 ]
  • [ 56-41-7 ]
  • [ 13404-22-3 ]
Reference: [1] Patent: US4730006, 1988, A,
  • 52
  • [ 56-41-7 ]
  • [ 104-15-4 ]
  • [ 100-51-6 ]
  • [ 42854-62-6 ]
YieldReaction ConditionsOperation in experiment
98.6% at 50 - 62℃; for 5.5 h; Into a 300 mL separable flask equipped with a thermometer, stirring apparatus and Dean Stark apparatus was charged 5.00 g (56.12 mmol) of L-alanine, 41.03 g (379.42 mmol) of benzyl alcohol and 12.81 g (67. 34 mmol) of p-toluenesulfonic acid, and mixed, then, the pressure was reduced from 101.3 kPa to 2.0 kPa. The reaction solution was heated, then, water started to be distilled at the inner temperature around 50°C, and the mixture was heated up to 62°C over a period of 2 hours. Under the same pressure and the same temperature, the mixture was stirred for 3.5 hours. The reaction solution was cooled down to 50°C, and 111.66 g of tert-butyl methyl ether was dropped over a period of 30 minutes, then, about 0.005 g (0.01 mmol) of p-toluenesulfonate of L-alanine benzyl ester was added. The mixture was stirred at 50°C for 30 minutes, then, 55.83 g of tert-butyl methyl ether was dropped over a period of 1 hour. The mixture was stirred at 50°C for 1 hour, then, cooled from 50°C to 0°C over a period of 5 hours, and the mixture was stirred at 0°C overnight. The mixture was subjected to a filtration treatment, and the resultant crystal was washed three times with 15.00 g of tert-butyl methyl ether of 0°C. After drying, 18.26 g of p-toluenesulfonate of L-alanine benzyl ester was obtained. The yield against L-alanine was 98.6percent. The optical purity of the p-toluenesulfonate of L-alanine benzyl ester was 99.9percent e.e. or more.
92% for 4 h; Dean-Stark; Reflux General procedure: The esterifications were carried out on L amino acids withthe exception of phenylglycine, the D enantiomer of whichwas used. A mixture of amino acid (0.05 mol), p-toluenesulfonicacid (0.06 mol), benzyl alcohol (0.25 mol) andcyclohexane (30 mL) was refluxed for 4 h using a Dean-Stark apparatus to separate water that was azeotroped outas it formed. The reaction mixture was cooled to roomtemperature and ethyl acetate (80 mL) was added. Afterstirring for 1 h, the precipitate was collected by filtrationand dried to give the corresponding benzyl ester p-toluenesulfonateas a white solid. According to this procedure,the amino acids 1–6 were converted into the correspondingbenzyl ester p-toluenesulfonates 1a–6a. The benzylationof 7 was accomplished in the same manner but in thepresence of more p-toluenesulfonic acid (0.11 mol) to givethe di-p-toluenesulfonate 7a as a white solid. The p-toluenesulfonate8a separated at the end of the reaction as anoil; instead of adding ethyl acetate, the supernatant wasremoved, the oily phase was washed with cyclohexane andthen poured into dichloromethane/aqueous Na2CO3. Afterremoving the water layer and evaporating dichloromethane,the residue was treated with hydrochloric methanol to give the corresponding hydrochloride as a white solid. Thebenzylation of 9 was prolonged over night and, at the endof the reaction, 9a separated as an oil, which was pouredinto dichloromethane/water. After removing the organiclayer, the water phase was made alkaline with NaHCO3 andextracted with ethyl acetate. The organic extract was concentratedto a small volume and a slight excess of p-toluenesulfonicacid was added to precipitate 9a as a white crystallinesolid.
72% Dean-Stark; Reflux To a solution of L-alanine (Scheme 2, compound 1-D) (1151.2 mg, 12.9 mmol, 1.00 eq) in 51 mL of toluene, were added (i) 23 mL of BnOH; and (ii) 2457.6 g of APTS.H2O (14.2 mmol, 1.10 eq). Overcoming a Dean-Stark assembly and a condenser, the mixture was stirred at reflux overnight. After completion of the reaction, the mixture was concentrated in vacuo, dissolved in EtOAc (20 mL) and extracted with 1M HCl (3×20 mL). The combined extracts were washed with ether (4×20 mL), adjusted to pH 8-9 with NaHCO3 and extracted with EtOAc (4×20 mL). The combined EtOAc extracts were dried (MgSO4), filtered through fritted glass and concentrated in vacuo. The residue was crystallized in a solution of APTS.H2O (2457.6 mg, mmol, 1 eq) in 20 mL of diethyl ether to give intermediate compound 1-E (Scheme 2) as a white solid (3260.0 mg, (72percent; MS (ES) m/z 180.1 (MH)+).
Reference: [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 2, p. 339 - 345
[2] Patent: EP2062873, 2009, A1, . Location in patent: Page/Page column 6
[3] Amino Acids, 2017, vol. 49, # 5, p. 965 - 974
[4] Patent: US2016/97052, 2016, A1, . Location in patent: Paragraph 0308
[5] Journal of Antibiotics, 1998, vol. 51, # 8, p. 786 - 794
[6] Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7215 - 7226
  • 53
  • [ 56-41-7 ]
  • [ 156-57-0 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 111 - 120
  • 54
  • [ 67-56-1 ]
  • [ 56-41-7 ]
  • [ 2491-20-5 ]
YieldReaction ConditionsOperation in experiment
100%
Stage #1: at -15 - 0℃;
Stage #2: for 3 h; Reflux
The L-alanine was used as substrate to produce (S)-alanine methyl ester hydrochloride (1a) according to the literature. (Xing et al., 2012). Add 15 mL of absolute methanol to the round bottom flask. Slow-drop 2.16 mL of SOCl2 (0.03 mol) into absolute methanol at −15 °C and maintained at 0 °C for an hour. Take 14 mL of absolute methanol and 1.4 mL (0.019 mol) of SOCl2 to another round bottom flask with the above steps. Then, 1.118 g of L-alanine were put into the solution and heating reflux for 1.5 h. After concentrated the solution under reduced pressure, the initial preparation of the SOCl2 solution was poured into the round bottom flask and continued reflux for 1.5 h to give 1a (yield 100percent). Since the hydrochloric acid produced in this step was not conducive to the next reaction, put NaHCO3 into the round bottom flask when reflux was ended to destroy its acidity until no more bubbles are generated. Finally, the solution was concentrated to afford 1b (yield 100percent).The fusaric acid (4) and 1b together with 15 mL of dichloromethane were put into a round bottom flask and stirred uniformly, then an excessof catalyst dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) were added and reflux for 24 h. Concentrated the solution under reduced pressure and the product was purified by using preparative HPLC (25–45percent CH3CN/H2O, 20 min) to obtain 1c (yield 52percent).
99% at 20℃; for 2 h; SOCl2 (21.8mL, 0.3mol) and (S)-alanine ((S)-19, 8.91g, 0.1mol) were added to CH3OH (100mL) and the mixture was stirred at RT for 2h. The solvent was removed in vacuo, the residue was dissolved in methanol (30mL) and the organic solvent was removed in vacuo again. This procedure was repeated twice. Colorless amorphous solid, mp 103°C (Ref. 39 mp 98–99°C), yield 14.3g (>99percent). [α]589=+7.9 (c=0.94, CH3OH) [Ref. 38 [α]589=+7.4 (c=1.76, CH3OH)].
98%
Stage #1: With thionyl chloride In water at -14 - -10℃; for 1 h;
Stage #2: for 4 h; Reflux
Take 125mL of methanol and add it to a 250mL three-necked flask (ensure that the environment is anhydrous during the reaction, with a drying device; the reaction will generate HCl and SO2 gas, use a lye absorption device) and cool it in a constant temperature reaction bath to - At 14°C, 10 mL (0.138 mol) of SOCl2 was slowly added dropwise with magnetic stirring. The reaction temperature was controlled to be below -10°C during the dropwise addition, and the reaction was continued for 1 h after the addition was completed. The reaction solution was transferred to a 250 mL round-bottomed flask, and the temperature was naturally raised to room temperature. 12.21 g (0.137 mol) of alanine was added and the reaction was stopped by heating to reflux under magnetic stirring for 4 hours. The product was evaporated and the solvent was distilled off to give alanine methyl ester hydrochloride as a yellow viscous liquid with a yield of 98percent. It can be used directly in the next step without purification.
96.4% at -5 - 20℃; General procedure: A suspension of L-amino acid (50mmol) in methanol (50mL) was stirred under ice cold conditions. Thionyl chloride (5mL) was slowly dropped to the solution at−5°C. Then, the mixture was allowed to slowly warm to room temperature while being stirred. The reaction was monitored by TLC (N-butanol: water: acetic acid=4:1:1). When the reaction was completed, the solvent was evaporated under reduced pressure to afford the crude product, which was recrystallized from methanol/ether to give a white solid.
7.7 g at -20 - 20℃; To a solution of L-alanine (5.0 g, 56 mmol) in methanol (60 mL) at -20°C was added dropwise thionyl chloride (6.1 mL, 84 mmol) and the mixture was stirred at ambient temperature overnight. The solvent was removed in vacuo. The solid residue was washed with diethyl ether, filtered and dried under vacuum to afford the title compound as a white solid (7.7 g). The crude product was used without further purification in subsequent reactions.1 H NMR (500 MHz, d4-MeOH) δ 4.1 1 (q, 1 H), 3.84 (s, 3H), 1.54 (d, 3H).
3.36 g at 20℃; for 6 h; Add L-alanine (2.5 g, 27.8 mmol) to a dry flask.Add anhydrous anaerobic methanol (278 mL), stir at 0 ° C for 10 min,Thionyl chloride (0.5 mL) was slowly added thereto, and the reaction was stirred for 6 hours.After the reaction was completed, the solvent was evaporated, diluted with diethyl ether and filtered.L-Alanine methyl ester 13 was obtained as a white solid, 3.36 g.

Reference: [1] Phytochemistry Letters, 2018, vol. 26, p. 50 - 54
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 36, p. 11683 - 11687[3] Angew. Chem., 2018, vol. 130, # 36, p. 11857 - 11861,5
[4] Journal of Organic Chemistry, 2008, vol. 73, # 7, p. 2898 - 2901
[5] Tetrahedron Asymmetry, 2009, vol. 20, # 9, p. 1036 - 1039
[6] European Journal of Organic Chemistry, 2015, vol. 2015, # 17, p. 3793 - 3805
[7] Journal of the American Chemical Society, 2017, vol. 139, # 40, p. 14077 - 14089
[8] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 17, p. 4778 - 4799
[9] Organic Preparations and Procedures International, 2002, vol. 34, # 1, p. 87 - 94
[10] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 8, p. 1942 - 1944
[11] Journal of the Chemical Society. Perkin Transactions 2, 2000, # 1, p. 69 - 76
[12] Helvetica Chimica Acta, 2007, vol. 90, # 3, p. 562 - 573
[13] European Journal of Organic Chemistry, 2010, # 22, p. 4276 - 4287
[14] Patent: CN105152949, 2017, B, . Location in patent: Paragraph 0045; 0046; 0055; 0056; 0065; 0066
[15] Journal of Organic Chemistry, 1989, vol. 54, # 4, p. 937 - 947
[16] Recueil des Travaux Chimiques des Pays-Bas, 1995, vol. 114, # 4-5, p. 171 - 174
[17] Bulletin des Societes Chimiques Belges, 1991, vol. 100, # 1, p. 63 - 77
[18] Chemical Biology and Drug Design, 2012, vol. 79, # 2, p. 216 - 222
[19] European Journal of Medicinal Chemistry, 2016, vol. 112, p. 196 - 208
[20] Journal of Medicinal Chemistry, 2015, vol. 58, # 15, p. 6293 - 6305
[21] Journal of Organometallic Chemistry, 1986, vol. 317, p. 93 - 104
[22] Tetrahedron Asymmetry, 2000, vol. 11, # 6, p. 1367 - 1374
[23] Synthetic Communications, 2018, vol. 48, # 12, p. 1487 - 1493
[24] Journal of the American Chemical Society, 1990, vol. 112, # 7, p. 2558 - 2566
[25] Journal of Pharmacy and Pharmacology, 1992, vol. 44, # 4, p. 295 - 299
[26] Organic and Biomolecular Chemistry, 2008, vol. 6, # 9, p. 1594 - 1600
[27] Research on Chemical Intermediates, 2013, vol. 39, # 2, p. 621 - 629
[28] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1197 - 1201
[29] Archiv der Pharmazie, 2011, vol. 344, # 8, p. 494 - 504
[30] Synthetic Communications, 2010, vol. 40, # 8, p. 1161 - 1179
[31] Journal of Chemical Research, Miniprint, 1981, # 9, p. 3261 - 3278
[32] European Journal of Inorganic Chemistry, 2012, # 20, p. 3349 - 3360
[33] Journal of the American Chemical Society, 1990, vol. 112, # 5, p. 1956 - 1961
[34] Tetrahedron, 1990, vol. 46, # 15, p. 5325 - 5332
[35] Heterocycles, 1991, vol. 32, # 10, p. 1879 - 1895
[36] Phosphorus and Sulfur and the Related Elements, 1987, vol. 29, p. 373 - 376
[37] Helvetica Chimica Acta, 1988, vol. 71, p. 1999 - 2021
[38] Archiv der Pharmazie, 1992, vol. 325, # 11, p. 709 - 715
[39] Phytochemistry (Elsevier), 1988, vol. 27, # 1, p. 77 - 84
[40] Journal of Physical Chemistry, 1994, vol. 98, # 27, p. 6862 - 6864
[41] Journal of Organometallic Chemistry, 1987, vol. 326, p. 289 - 298
[42] Tetrahedron Letters, 2002, vol. 43, # 21, p. 3935 - 3937
[43] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 6, p. 1629 - 1632
[44] Tetrahedron Asymmetry, 2002, vol. 13, # 18, p. 2053 - 2059
[45] Canadian Journal of Chemistry, 2005, vol. 83, # 8, p. 1164 - 1170
[46] Chemical Communications, 2005, # 28, p. 3562 - 3564
[47] Tetrahedron, 2007, vol. 63, # 31, p. 7334 - 7348
[48] Patent: EP1903034, 2008, A1, . Location in patent: Page/Page column 7
[49] Chemical Communications, 2006, # 29, p. 3081 - 3083
[50] Tetrahedron, 2009, vol. 65, # 45, p. 9116 - 9124
[51] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 6, p. 2135 - 2140
[52] Patent: WO2010/122134, 2010, A1, . Location in patent: Page/Page column 65
[53] European Journal of Organic Chemistry, 2008, # 14, p. 2423 - 2429
[54] Synlett, 2009, # 8, p. 1227 - 1232
[55] European Journal of Medicinal Chemistry, 2009, vol. 44, # 7, p. 2796 - 2806
[56] Zeitschrift fur Anorganische und Allgemeine Chemie, 2010, vol. 636, # 1, p. 236 - 241
[57] Journal of Chemical Research, 2011, vol. 35, # 1, p. 47 - 50
[58] Journal of Chemical Research, 2012, vol. 36, # 4, p. 206 - 209
[59] Chemistry - An Asian Journal, 2011, vol. 6, # 1, p. 189 - 197
[60] Letters in Organic Chemistry, 2011, vol. 8, # 3, p. 210 - 215
[61] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1227 - 1236
[62] Organic Letters, 2012, vol. 14, # 5, p. 1318 - 1321
[63] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 12, p. 3807 - 3815
[64] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1170 - 1174
[65] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1237 - 1241
[66] Biomacromolecules, 2012, vol. 13, # 8, p. 2446 - 2455
[67] Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3361 - 3368
[68] Asian Journal of Chemistry, 2013, vol. 25, # 3, p. 1749 - 1750
[69] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 5, p. 1067 - 1070
[70] RSC Advances, 2013, vol. 3, # 40, p. 18332 - 18338
[71] Chemical Communications, 2014, vol. 50, # 4, p. 433 - 435
[72] Applied Organometallic Chemistry, 2014, vol. 28, # 7, p. 545 - 551
[73] Organic and Biomolecular Chemistry, 2014, vol. 12, # 41, p. 8318 - 8324
[74] Chemistry--A European Journal, 2014, vol. 20, # 36, p. 11428 - 11438,11
[75] Medicinal Chemistry Research, 2015, vol. 24, # 7, p. 2825 - 2837
[76] European Journal of Medicinal Chemistry, 2016, vol. 108, p. 166 - 176
[77] Journal of Polymer Science, Part A: Polymer Chemistry, 2016, vol. 54, # 8, p. 1065 - 1077
[78] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 637 - 648
[79] Patent: WO2017/36880, 2017, A1, . Location in patent: Paragraph 200
[80] Organic Syntheses, 1988, vol. 66, p. 151 - 151
[81] Journal of Medicinal Chemistry, 2017, vol. 60, # 13, p. 5889 - 5908
[82] Patent: WO2017/129829, 2017, A1, . Location in patent: Page/Page column 31; 32
[83] Russian Chemical Bulletin, 2017, vol. 66, # 1, p. 136 - 142[84] Izv. Akad. Nauk, Ser. Khim., 2017, # 1, p. 136 - 142,6
[85] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 2, p. 501 - 508
[86] Chemistry - An Asian Journal, 2018, vol. 13, # 4, p. 400 - 403
[87] Patent: CN107880023, 2018, A, . Location in patent: Paragraph 0104; 0105; 0106
[88] Patent: CN108069867, 2018, A, . Location in patent: Paragraph 0015-0017
[89] Patent: CN107827815, 2018, A, . Location in patent: Paragraph 0108; 0109; 0128; 0129; 0148; 0149
[90] Journal of Organometallic Chemistry, 2018, vol. 876, p. 1 - 9
[91] Amino Acids, 2018, vol. 50, # 10, p. 1461 - 1470
[92] Patent: CN108690005, 2018, A, . Location in patent: Paragraph 0036; 0037
  • 55
  • [ 56-41-7 ]
  • [ 2491-20-5 ]
Reference: [1] Tetrahedron, 1988, vol. 44, # 6, p. 1685 - 1690
[2] Patent: US5496927, 1996, A,
[3] Patent: US5113009, 1992, A,
[4] Patent: US2006/287500, 2006, A1, . Location in patent: Page/Page column 2; 3
  • 56
  • [ 56-41-7 ]
  • [ 77-76-9 ]
  • [ 2491-20-5 ]
Reference: [1] Organic Letters, 2008, vol. 10, # 7, p. 1469 - 1472
[2] Tetrahedron Asymmetry, 2008, vol. 19, # 1, p. 67 - 81
  • 57
  • [ 13165-72-5 ]
  • [ 56-41-7 ]
  • [ 2491-20-5 ]
Reference: [1] Chemistry and Biodiversity, 2018, vol. 15, # 5,
  • 58
  • [ 56-41-7 ]
  • [ 75-36-5 ]
  • [ 2491-20-5 ]
Reference: [1] European Journal of Organic Chemistry, 2013, # 26, p. 5838 - 5847
  • 59
  • [ 56-41-7 ]
  • [ 74-88-4 ]
  • [ 2491-20-5 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 2004, vol. 77, # 6, p. 1187 - 1193
  • 60
  • [ 64-17-5 ]
  • [ 56-41-7 ]
  • [ 1115-59-9 ]
YieldReaction ConditionsOperation in experiment
80% at -5 - 78℃; for 1.5 h; Reflux General procedure: A mixture of alanine (3.56 g, 0.04 mol) in ethanol (30 mL), with thionyl chloride (3.6 mL) dropwise added at -5 °C, was refluxed in ethanol at 78 °C under stirring within 1.5 h. Subsequently, the solution was distilled in vacuum to afford Alanine ethyl ester hydrochloride 2a in >80percent yield. The physical constants of 2a-2l are identical with the corresponding data in reference [24].
Reference: [1] Chemical Communications, 2011, vol. 47, # 26, p. 7347 - 7349
[2] Dalton Transactions, 2015, vol. 44, # 3, p. 1170 - 1177
[3] Tetrahedron, 1999, vol. 55, # 11, p. 3337 - 3354
[4] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 8, p. 1942 - 1944
[5] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1994, # 7, p. 1455 - 1462
[6] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1197 - 1201
[7] European Journal of Inorganic Chemistry, 2003, # 11, p. 2113 - 2122
[8] Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, 1980, vol. 76, p. 915 - 922
[9] Journal of the Indian Chemical Society, 2001, vol. 78, # 3, p. 137 - 141
[10] European Journal of Medicinal Chemistry, 2011, vol. 46, # 1, p. 11 - 20
[11] Tetrahedron, 2008, vol. 64, # 7, p. 1301 - 1308
[12] Chemistry of Natural Compounds, 1994, vol. 30, # 2, p. 238 - 244[13] Khimiya Prirodnykh Soedinenii, 1994, # 2, p. 261 - 268
[14] Tetrahedron, 1990, vol. 46, # 15, p. 5325 - 5332
[15] Journal of Organometallic Chemistry, 1981, vol. 221, # 2, p. 203 - 222
[16] Helvetica Chimica Acta, 1995, vol. 78, p. 109 - 121
[17] Tetrahedron, 2007, vol. 63, # 14, p. 3031 - 3041
[18] Advanced Synthesis and Catalysis, 2012, vol. 354, # 2-3, p. 295 - 300
[19] Green Chemistry, 2012, vol. 14, # 5, p. 1350 - 1356
[20] Chemistry of Natural Compounds, 2012, vol. 48, # 2, p. 194 - 197
[21] Tetrahedron, 2012, vol. 68, # 49, p. 10218 - 10229,12
[22] Tetrahedron, 2012, vol. 68, # 49, p. 10218 - 10229
[23] Nucleosides, Nucleotides and Nucleic Acids, 2013, vol. 32, # 4, p. 161 - 173
[24] Patent: US2016/264611, 2016, A1, . Location in patent: Paragraph 0222; 0223; 0224
[25] International Journal of Pharmaceutics, 2018, vol. 546, # 1-2, p. 31 - 38
  • 61
  • [ 56-41-7 ]
  • [ 1115-59-9 ]
Reference: [1] Patent: US5801249, 1998, A,
  • 62
  • [ 56-41-7 ]
  • [ 13515-97-4 ]
Reference: [1] Patent: US5455258, 1995, A,
[2] Patent: US5506242, 1996, A,
[3] Patent: US5552419, 1996, A,
  • 63
  • [ 56-41-7 ]
  • [ 100-51-6 ]
  • [ 100836-85-9 ]
  • [ 33106-32-0 ]
Reference: [1] Journal of Organic Chemistry, 1988, vol. 53, # 15, p. 3457 - 3465
  • 64
  • [ 56-41-7 ]
  • [ 6003-05-0 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1987, p. 323 - 328
[2] Journal of Physical Chemistry B, 2010, vol. 114, # 37, p. 12157 - 12161
[3] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2015, vol. 136, # PB, p. 743 - 750
[4] Journal of Molecular Structure, 2018, vol. 1163, p. 428 - 441
  • 65
  • [ 67-56-1 ]
  • [ 56-41-7 ]
  • [ 28920-43-6 ]
  • [ 84000-07-7 ]
Reference: [1] Tetrahedron Letters, 1997, vol. 38, # 42, p. 7307 - 7310
  • 66
  • [ 56-41-7 ]
  • [ 456-42-8 ]
  • [ 130855-56-0 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1990, vol. 39, # 7.2, p. 1479 - 1485[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1990, # 7, p. 1630 - 1636
  • 67
  • [ 56-41-7 ]
  • [ 104-15-4 ]
  • [ 107-18-6 ]
  • [ 20845-17-4 ]
Reference: [1] Liebigs Annalen der Chemie, 1983, # 10, p. 1712 - 1725
[2] Helvetica Chimica Acta, 2002, vol. 85, # 11, p. 3785 - 3791
[3] Organic Letters, 2003, vol. 5, # 3, p. 235 - 237
  • 68
  • [ 56-41-7 ]
  • [ 67-63-0 ]
  • [ 39613-92-8 ]
YieldReaction ConditionsOperation in experiment
100% at 80 - 85℃; for 4 h; Inert atmosphere To a flask provided with mechanical stirrer, reflux condenser, thermometer and under nitrogen atmosphere are added (L)-alanine (5.0 g, 56.1 mmol) and a solution of hydrogen chloride in isopropanol (1 1 .1 percent w/w, 73.8 g, 224.5 mmol). The reaction mixture is heated to boiling (80-85 °C) for 4 hours. Once the conversion is complete, controlled in TLC by eluting with 7:3 ethanol-water and developing with ninhydrin, it is concentrated to residue in vacuum removing the /'so-propanol co-evaporating the residue multiple times with isopropyl acetate, thus obtaining the desired product (9.4 g quantitative yield) as an oil.
94% for 5 h; Reflux Thionyl chloride (80 g, 49.2 mL, 673 mmol) was added dropwise over a 30 mill period to a suspension of L-alanine (50g, 561 mmol) in isopropanol (500 mL). The mixture was heated to a gentle reflux for 5h and then concentrated by rotary evaporator (bath set at60°C). The resulting thick gum solidified upon trituration with ether (150 ml). The whitepowder was triturated a second time with ether (150 mL), collected by filtration while under astream of argon, and then dried under high vacuum for 1 8h to give (S)-isopropyl 2-aminopropanoate hydrochloride (88 g, 94percent).‘H NMR (400 MHz, DMSO-d6) ö 8.62 (s, 3H), 5.10—4.80 (m, 1H), 3.95 (q, J= 7.2 Hz, 1H),1.38 (d, J= 7.2 Hz, 3H), 1.22 (d, J= 4.6 Hz, 3H), 1.20 (d, J 4.6 Hz, 3H).
94% for 5.5 h; Reflux Example 90. General Procedure for the Preparation of 5’-Phosphoramidate Prodrugs Synthesis of chlorophosphoramidate: Thionyl chloride (80 g, 49.2 mL, 673 mmol) was added dropwise over a 30 min period to a suspension of L-alanine (50g, 561 mmol) in isopropanol (500 mL). The mixture was heated to a gentle reflux for 5h and then concentrated by rotary evaporator (bath set at 60oC). The resulting thick gum solidified upon trituration with ether (150 ml). The white powder was triturated a second time with ether (150 mL), collected by filtration while under a stream of argon, and then dried under high vacuum for 18h to give (S)-isopropyl 2- aminopropanoate hydrochloride (88 g, 94percent). 1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 3H), 5.10– 4.80 (m, 1H), 3.95 (q, J = 7.2 Hz, 1H), 1.38 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 4.6 Hz, 3H), 1.20 (d, J = 4.6 Hz, 3H).
94% for 5.5 h; Reflux Thionyl chloride (80 g, 49.2 mL, 673 mmol) was added dropwise over a 30 min period to a suspension of L-alanine (50g, 561 mmol) in isopropanol (500 mL). The mixture was heated to a gentle reflux for 5h and then concentrated by rotary evaporator (bath set at 60°C). The resulting thick gum solidified upon trituration with ether (150 ml). The white powder was triturated a second time with ether (150 mL), collected by filtration while under a stream of argon, and then dried under high vacuum for 18h to give (S)-isopropyl 2-aminopropanoate hydrochloride (88 g, 94percent). 1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 3H), 5.10 - 4.80 (m, 1H), 3.95 (q, J = 7.2 Hz, 1H), 1.38 (d, J = 7.2 Hz, 3H), 1.22 (d, J= 4.6 Hz, 3H), 1.20 (d, J = 4.6 Hz, 3H).
94% for 5 h; Reflux Thionyl chloride (80 g, 49.2 mL, 673 mmol) was added dropwise over a 30 min period to a suspension of L-alanine (50g, 561 mmol) in isopropanol (500 mL). The mixture was heated to a gentle reflux for 5h and then concentrated by rotary evaporator (bath set at 60°C). The resulting thick gum solidified upon trituration with ether (150 ml). The white powder was triturated a second time with ether (150 mL), collected by filtration while under a stream of argon, and then dried under high vacuum for 18h to give (S)-isopropyl 2- aminopropanoate hydrochloride (88 g, 94percent). NMR (400 MHz, DMSO-c e) δ 8.62 (s, 3H), 5.10 - 4.80 (m, 1H), 3.95 (q, J= 7.2 Hz, 1H), 1.38 (d, J= 7.2 Hz, 3H), 1.22 (d, J = 4.6 Hz, 3H), 1.20 (d, J= 4.6 Hz, 3H).
90%
Stage #1: at 0℃; for 0.5 h;
Stage #2: With sodium hydroxide In water at 20 - 70℃;
Thionylchloride (80.2 g, 0.674 mol,1 .5 eq) was added with cooling to 2-propanol (400 ml_) at -7 to 0°C over a period of 30 minutes, followed by addition of L-alanine (40.0 g, 0.449 mol) at 0 °C. A flow indicator and a scrubber with a mixture of 27.65percent sodium hydroxide (228 g) and water (225 g) were attached to the outlet. The reaction mixture was stirred at 67 °C for two hours, then at 70 °C for one hour and at 20 - 25 °C over night. The reaction mixture was distilled at 47-50°C under reduced pressure (250 - 50 mBar) from a 60 °C bath. When the distillation became very slow, toluene (100 ml_) was added to the residual oil, and the distillation at 48-51 °C under reduced pressure (150 - 50 mBar) from a 60 °C bath was continued until it became very slow, t- butylmethylether (tBME)(400 ml_) was added to the residual oil, and the two-phase system ws seeded under efficient stirring at 34 - 35°C. When crystallization was observed the mixture was cooled to 23 °C over a period of one hour, and the precipitate isolated by filtration. The filter cake was washed with tBME (100 ml_) and dried to constant weight under reduced pressure without heating, which gave the title compound (67.7 g, 90percent) as white solids.
90%
Stage #1: at -7 - 0℃; for 0.5 h;
Stage #2: at 67 - 70℃;
Thionyl chloride (80.2 g, 0.674 mol, 1.5 eq) was added to 2-propanol (400 mL) at -7 to 0 ° C with cooling over 30 min followed by the addition of L-alanine (40.0 g, 0.449 mol). A flow indicator and a scrubber with a mixture of 27.65percent sodium hydroxide (228 g) and water (225 g) were connected to the outlet. The reaction mixture was stirred at 67 ° C for two hours, then at 70 ° C for one hour and at 20-25 ° C overnight. The reaction mixture was distilled at 47-50 ° C under reduced pressure (250-50 mbar) in a 60 ° C bath. When the distillation became very slow, toluene (100 mL) was added to the residual oil and the distillation was continued at 48-51 ° C under reduced pressure (150-50 mbar) in a 60 ° C bath until it became very abnormal slow. Tert-butyl methyl ether (tBME) (400 mL) was added to the residual oil and the biphasic system was seeded with efficient stirring at 34-35 ° C. When crystallization was observed, the mixture was cooled to 23 ° C over a period of one hour, and the precipitate was isolated by filtration. The filter cake was washed with tBME (100 mL) and dried under reduced pressure to constant weight without heating to give the title compound (67.7 g, 90percent) as a white solid.

Reference: [1] Patent: WO2016/151542, 2016, A1, . Location in patent: Page/Page column 19
[2] European Journal of Organic Chemistry, 2018, vol. 2018, # 20, p. 2622 - 2628
[3] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1197 - 1201
[4] Patent: WO2015/38596, 2015, A1, . Location in patent: Page/Page column 237; 238
[5] Patent: WO2016/145142, 2016, A1, . Location in patent: Page/Page column 287
[6] Patent: WO2017/106710, 2017, A1, . Location in patent: Page/Page column 77
[7] Patent: WO2017/155923, 2017, A1, . Location in patent: Page/Page column 152
[8] Patent: WO2016/30335, 2016, A1, . Location in patent: Page/Page column 50
[9] Patent: CN107405356, 2017, A, . Location in patent: Paragraph 0210; 0211; 0212
[10] Molecular Pharmaceutics, 2010, vol. 7, # 6, p. 2349 - 2361
[11] Nucleosides, Nucleotides and Nucleic Acids, 2001, vol. 20, # 4-7, p. 621 - 628
[12] ChemSusChem, 2011, vol. 4, # 5, p. 604 - 608
[13] Patent: US2014/248242, 2014, A1, . Location in patent: Paragraph 0361; 0366
[14] Patent: WO2015/107451, 2015, A2, . Location in patent: Page/Page column 7
[15] Patent: WO2017/189978, 2017, A1, . Location in patent: Page/Page column 316
  • 69
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  • [ 73724-40-0 ]
  • [ 87512-31-0 ]
YieldReaction ConditionsOperation in experiment
1.77 g With sodium hydrogencarbonate In tetrahydrofuran; water at 25℃; for 5 h; Example 1 Preparation oflsT-Fmoc-Ala-Ala [I] A solution of Na-Fmoc-Ala (1.58 g, 5.0 mmoles), N-hydroxyl succinimide (0.63 g, 5.5 mmoles) and DCC (1.03 g, 5.0 mmoles) in CH2C12 (50 mL) were stirred at 5 °C for 6 hours. The DCU was filtered out and the filtrate was concentrated. Residue was re-dissolved in THF (50 mL) and kept in refrigerator (4°C) overnight. More DCU was filtered off and the THF solution was added to a solution of alanine (0.99 g, 7.5 mmoles) and NaHC03 (1.68 g, 20 mmoles) in 25percent THF/H20 (80 mL). The reaction mixture was stirred vigorously at 25°C for 5 hours. THF was removed by concentration and the aqueous suspension was adjusted to pH4 with concentrated HC1. The aqueous suspension was stirred at 25 °C for another 3 hours and the precipitate was collected by filtration, rinsed thoroughly with de-salt water and was dried in vacuum over KOH to give a white solid product (1.77 g, 83.7percent yield). LC/MS: (MH)+ = 383
Reference: [1] Journal of the American Chemical Society, 2003, vol. 125, # 45, p. 13680 - 13681
[2] Patent: WO2015/187540, 2015, A1, . Location in patent: Page/Page column 22; 23
[3] Patent: WO2016/94505, 2016, A1, . Location in patent: Paragraph 000457
[4] Patent: WO2017/214456, 2017, A1, . Location in patent: Page/Page column 296
  • 70
  • [ 56-41-7 ]
  • [ 86060-86-8 ]
  • [ 87512-31-0 ]
Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 11, p. 2328 - 2332
  • 71
  • [ 56-41-7 ]
  • [ 130878-68-1 ]
  • [ 150114-97-9 ]
YieldReaction ConditionsOperation in experiment
85% With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; 2.0 g of Fmoc-Val-OSu (4.58 mmol, 1 eq) diluted in 10 mL THF was added to a solution of 0.43 g H-Ala-OH (4.81 mmol, 1.05 eq) and a solution of 0.40 g NaHCO3 (4.81 mmol, 1.05 eq) dissolved in 15 mL H2O. Immediately, the colorless solution turned turbid. A mixture of H2O, THF and diethyl ether (60 mL, 1:1:1) was added until a clear solution resulted. The solution was stirred well at room temperature. After a week the solvents were removed under reduced pressure and 30 mL citric acid (15percent aqueous) and 50 mL ethyl acetate were added and the mixture was stirred for one hour at room temperature. The phases were separated and the aqueous layer was extracted three times (3×100 mL) with ethyl acetate. The combined organic phases were dried, and the solvent was evaporated. Afterwards, the residue was purified by flash chromatography on silica gel (CHCl3/MeOH 30:1+1percent AcOH) to give a colorless solid (1.60 g, 85percent). 1H NMR (DMSO-d6): δ[ppm] 0.87 (d, 3H, J=6.8 Hz), 0.90 (d, 3H, J=6.8 Hz), 1.27 (d, 3H, J=7.3 Hz), 1.94-2.06 (m, 1H), 3.90 (t, 1H, J=7.2 Hz), 4.17-4.31 (m, 4H), 7.30-7.35 (m, 2H), 7.39-7.44 (m, 3H), 7.76 (t, 2H, J=6.6 Hz), 7.89 (d, 2H, J=7.5 Hz), 8.22 (d, 1H, J=6.9 Hz), 12.50 (bs, 1H). 13C NMR (DMSO-d6): δ[ppm] 17.5, 18.6, 19.6, 30.9, 47.1, 47.9, 60.2, 66.1, 120.5, 125.8, 127.5, 128.1, 141.1, 144.2, 144.3, 156.5, 171.4, 174.4.
74% With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 50 h; Step 2 product is prepared in analogy to P.W. Howard et al. US 2011/0256157. A solution of L-alanine (5.58 g; 1.05 eq.) and sodium hydrogen carbonate (5.51 g; 1.1 eq.) in 150 ml water was prepared and added to a solution of HOP 30.1343 (26.51 g; max. 59.6 mmol) in 225 ml tetrahydrofuran. The mixture was stirred for 50 h at RT. After consumption of starting material the solution was partitioned between 240 ml of 0.2 M citric acid and 200 ml of ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate (3 x 200 ml). The combined organic layers were washed with water and brine (300 ml each) dried (Mg504) and the solvent was evaporated to approx. 200 ml. Pure product precipitated at this time and was filtered off. The mother liquor was evaporated to dryness and the residue was stirred 1 h with 100 ml MTBE to result additional crystalline material. The two crops of product were combined to 18.01 g (74percent) white powder. (m.p.: 203-207°C)
18.01 g With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 50 h; product is prepared in analogy to P.W. Howard et al. US 2011/0256157. A solution of L-alanine (5.58 g; 1.05 eq.) and sodium hydrogen carbonate (5.51 g; 1.1 eq.) in 150 ml water was prepared and added to a solution of HDP 30.1343 (26.51 g; max. 59.6 mmol) in 225 ml tetrahydrofuran. The mixture was stirred for 50 h at RT. After consumption of starting material the solution was partitioned between 240 ml of 0.2 M citric acid and 200 ml of ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate (3 x 200 ml). The combined organic layers were washed with water and brine (300 ml each) dried (MgS04) and the solvent was evaporated to approx. 200 ml. Pure product precipitated at this time and was filtered off. The mother liquor was evaporated to dryness and the residue was stirred 1 h with 100 ml MTBE to result additional crystalline material. The two crops of product were combined to 18.01 g (74percent) white powder, (m.p.: 203-207X) [ +Naf found: 410.94; calc: 41 1.19 (C23H27N2O5) [M+Naf found: 433.14; calc: 433.17 (C23H27N2O5) [2M+H]+ found: 842.70; calc: 843.36 (C46H52N4NaO10)
Reference: [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 17, p. 7502 - 7515
[2] Patent: US2014/51623, 2014, A1, . Location in patent: Paragraph 0063-0066
[3] Patent: WO2018/115466, 2018, A1, . Location in patent: Paragraph 00103; 00124; 00126
[4] Patent: WO2017/149077, 2017, A1, . Location in patent: Paragraph 00130
  • 72
  • [ 56-41-7 ]
  • [ 68858-20-8 ]
  • [ 150114-97-9 ]
Reference: [1] International Journal of Molecular Sciences, 2017, vol. 18, # 9,
[2] Patent: WO2016/94509, 2016, A1, . Location in patent: Paragraph 0001118
[3] Patent: WO2017/214458, 2017, A2, . Location in patent: Page/Page column 479
[4] Patent: WO2017/214301, 2017, A1, . Location in patent: Page/Page column 428
[5] Patent: WO2017/214462, 2017, A2, . Location in patent: Page/Page column 627
[6] Patent: WO2017/214456, 2017, A1, . Location in patent: Page/Page column 368
[7] Patent: US2017/355769, 2017, A1, . Location in patent: Paragraph 2097
  • 73
  • [ 56-41-7 ]
  • [ 68858-20-8 ]
  • [ 77-92-9 ]
  • [ 150114-97-9 ]
Reference: [1] Patent: US2016/158377, 2016, A1, . Location in patent: Paragraph 1060
  • 74
  • [ 56-41-7 ]
  • [ 86060-87-9 ]
  • [ 150114-97-9 ]
Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 11, p. 2328 - 2332
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Aminomalonic acid

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