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[ CAS No. 37784-17-1 ] {[proInfo.proName]}

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Chemical Structure| 37784-17-1
Chemical Structure| 37784-17-1
Structure of 37784-17-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 37784-17-1 ]

CAS No. :37784-17-1 MDL No. :MFCD00063226
Formula : C10H17NO4 Boiling Point : -
Linear Structure Formula :- InChI Key :ZQEBQGAAWMOMAI-SSDOTTSWSA-N
M.W :215.25 Pubchem ID :688022
Synonyms :

Calculated chemistry of [ 37784-17-1 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.8
Num. rotatable bonds : 4
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 58.36
TPSA : 66.84 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) : -6.57 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.99
Log Po/w (XLOGP3) : 1.47
Log Po/w (WLOGP) : 1.09
Log Po/w (MLOGP) : 0.74
Log Po/w (SILICOS-IT) : 0.22
Consensus Log Po/w : 1.1

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.84
Solubility : 3.14 mg/ml ; 0.0146 mol/l
Class : Very soluble
Log S (Ali) : -2.48
Solubility : 0.712 mg/ml ; 0.00331 mol/l
Class : Soluble
Log S (SILICOS-IT) : -0.38
Solubility : 90.6 mg/ml ; 0.421 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.62

Safety of [ 37784-17-1 ]

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 [ 37784-17-1 ]

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

  • Upstream synthesis route of [ 37784-17-1 ]
  • Downstream synthetic route of [ 37784-17-1 ]

[ 37784-17-1 ] Synthesis Path-Upstream   1~24

  • 1
  • [ 37784-17-1 ]
  • [ 73365-02-3 ]
YieldReaction ConditionsOperation in experiment
11.1 g
Stage #1: With oxalyl dichloride; triethylamine In dichloromethane; dimethyl sulfoxide at -78℃; for 1.15 h; Inert atmosphere
Stage #2: at -78℃; for 1 h; Inert atmosphere
To a solution of oxalyl chloride (6.39 mL, 75 mmol) in DCM (200 mL) at -78 00 under nitrogen, was added DMSO (10.66 mL, 150 mmol) dropwise, the reaction mixture was stirred at -78 00 for 15 mins. (Teit-butoxycarbonyl)-D-proline (10.0 g, 46.4 mmol) in DCM (50 mL) was added dropwise to the reaction mixture at -78 00 over 1 h and thenthe reaction mixture was stirred at -78 00 for 15 mins. Et3N (28 mL, 200 mmol) was added dropwise to the reaction mixture at -78 00 the reaction mixture was warmed to 0 00 and stirred for 1 h under nitrogen. The reaction mixture was quenched with saturated NaHCO3 (aq) (200 mL), combined aqueous layers washed with DCM (100 mL), the organic layers were combined, dried (Na2SO4) and solvents were removed invacuo to give crude teit-butyl (2R)-2-formylpyrrolidine-1-carboxylate (11.1 g, 100percent) asa colourless oil. Used directly without further purification
Reference: [1] Organic Letters, 2006, vol. 8, # 23, p. 5357 - 5360
[2] European Journal of Medicinal Chemistry, 2000, vol. 35, # 11, p. 979 - 988
[3] Journal of Medicinal Chemistry, 1992, vol. 35, # 9, p. 1550 - 1557
[4] Journal of Medicinal Chemistry, 1990, vol. 33, # 12, p. 3190 - 3198
[5] Tetrahedron Letters, 1990, vol. 31, # 28, p. 3957 - 3960
[6] Patent: US2011/263561, 2011, A1,
[7] Nature, 2014, vol. 509, # 7500, p. 318 - 324
[8] RSC Advances, 2016, vol. 6, # 31, p. 25713 - 25723
[9] Patent: WO2017/21728, 2017, A1, . Location in patent: Page/Page column 53
  • 2
  • [ 37784-17-1 ]
  • [ 74-88-4 ]
  • [ 73323-65-6 ]
YieldReaction ConditionsOperation in experiment
65% With potassium carbonate In tetrahydrofuran for 17 h; Reflux To a mixture of (R)- 1 -(tert-butoxycarbonyl)pyffolidine-2-carboxylic acid (5) (5.8 g, 27 mmol) and potassium carbonate (8.6 g, 62 mmol) in tetrahydrofuran (160 mL) was added iodomethane (4.0 mL, 65 mmol). The resultant mixture was heated at reflux for 17 hours andthen cooled to room temperature. The mixture was then filtered and the filtrate was concentrated in vacuo and purified by automated column chromatography using petroleum ether:ethyl acetate (3:1) as the eluent to afford (R)-1-tert-butyl 2-methyl pyrrolidine-1,2-dicarboxylate (6) (6.0 g, 65percent) as a yellow oil.
Reference: [1] Patent: WO2013/131018, 2013, A1, . Location in patent: Page/Page column 38
  • 3
  • [ 37784-17-1 ]
  • [ 77-78-1 ]
  • [ 73323-65-6 ]
Reference: [1] Journal of Organic Chemistry, 1999, vol. 64, # 21, p. 8014 - 8017
  • 4
  • [ 186581-53-3 ]
  • [ 37784-17-1 ]
  • [ 73323-65-6 ]
Reference: [1] Journal of Organic Chemistry, 1980, vol. 45, # 11, p. 2145 - 2151
  • 5
  • [ 37784-17-1 ]
  • [ 35150-07-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3524 - 3548
  • 6
  • [ 24424-99-5 ]
  • [ 344-25-2 ]
  • [ 37784-17-1 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: With sodium hydrogencarbonate In 1,4-dioxane; water at 20℃; for 0.5 h;
Stage #2: at 0 - 20℃;
Step- 1 : Synthesis of N-tert-butoxycarbonyl-(D)-Proline: [0264] To a stirred solution of D-proline (100 g, 868.58 mmol) in dioxane (400 mL, 8 vol) was added NaHC03 (182.4 g, 2.5 eq.) and water (800 mL, 8 vol) at room temperature and stirred the reaction mixture for about 30 minutes. The reaction mixture was cooled to 0- 5°C temperature and Di-tert-butyl dicarbonate (BOC)20 (224.26 g, 1.2 eq.) was added and stirred for 1 h at 0-5°C. Then the reaction mixture was warmed to room temperature and stirred for over night (12-16 hours). Reaction mixture was monitored by TLC, after completion of reaction, solvent dioxane was evaporated. The aqueous layer was acidified with 4N HC1 solution to PH 2 to 3 at 0-5 °C. The Aqueous layer was extracted with ethyl acetate (4X 200 mL) and combined organic layer was washed with water and dried over Na2S04. Organic layer was evaporated under reduced pressure to provide a white solid. The obtained white solid was taken in to heptane (200 mL) and stirred for about 2 hours at room temperature. Filtered the solid and dried the compound under vacuum at 45-50°C temperature (Wt: 125 g, Yield: 90-95percent). 1H NMR (300 MHz, CDC13): δ 9.20 (br, lH), 4.34 (t, 1H), 3.54- 3.13 (m, 2H), 2.31-2.25 (m, 1H), 2.09-1.88 (m, 3H), 1.48-1.42 (b, 9H); Mass: [M+Na]+ 238 (100percent).
Reference: [1] European Journal of Medicinal Chemistry, 2011, vol. 46, # 8, p. 3455 - 3461
[2] Patent: WO2014/105926, 2014, A1, . Location in patent: Paragraph 0264
[3] Synthetic Communications, 2009, vol. 39, # 18, p. 3243 - 3253
[4] Journal of Medicinal Chemistry, 1998, vol. 41, # 3, p. 284 - 290
[5] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 20, p. 2691 - 2696
[6] Patent: US4576749, 1986, A,
[7] Chirality, 2010, vol. 22, # 1, p. 173 - 181
[8] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3524 - 3548
[9] Patent: US2011/263561, 2011, A1, . Location in patent: Page/Page column 15
[10] Journal of Organic Chemistry, 2014, vol. 79, # 6, p. 2694 - 2701
[11] Nature, 2014, vol. 509, # 7500, p. 318 - 324
[12] Tetrahedron, 2016, vol. 72, # 35, p. 5369 - 5376
[13] Patent: WO2017/17630, 2017, A1, . Location in patent: Page/Page column 49
  • 7
  • [ 124-38-9 ]
  • [ 86953-79-9 ]
  • [ 37784-17-1 ]
Reference: [1] Organic Letters, 2010, vol. 12, # 10, p. 2222 - 2225
  • 8
  • [ 344-25-2 ]
  • [ 37784-17-1 ]
Reference: [1] Patent: US5008245, 1991, A,
  • 9
  • [ 1294505-66-0 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4168 - 4172
  • 10
  • [ 1294505-64-8 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4168 - 4172
  • 11
  • [ 58632-95-4 ]
  • [ 344-25-2 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Medicinal Chemistry, 2000, vol. 43, # 20, p. 3792 - 3798
  • 12
  • [ 350022-46-7 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 9, p. 3076 - 3086
  • 13
  • [ 73286-71-2 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Organic Chemistry, 1980, vol. 45, # 11, p. 2145 - 2151
  • 14
  • [ 73365-02-3 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Organic Chemistry, 1980, vol. 45, # 11, p. 2145 - 2151
  • 15
  • [ 86953-79-9 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 9, p. 3076 - 3086
  • 16
  • [ 124-38-9 ]
  • [ 86953-79-9 ]
  • [ 15761-39-4 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of the American Chemical Society, 1994, vol. 116, # 8, p. 3231 - 3239
  • 17
  • [ 15761-39-4 ]
  • [ 37784-17-1 ]
Reference: [1] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4168 - 4172
[2] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4168 - 4172
  • 18
  • [ 37784-17-1 ]
  • [ 60419-23-0 ]
Reference: [1] Journal of Medicinal Chemistry, 1992, vol. 35, # 23, p. 4334 - 4343
[2] Patent: WO2017/17630, 2017, A1,
  • 19
  • [ 37784-17-1 ]
  • [ 70138-72-6 ]
YieldReaction ConditionsOperation in experiment
54%
Stage #1: With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -78℃; for 1 h;
Stage #2: With ammonia In tetrahydrofuran; water at -78 - 20℃; for 2 h;
Example 1; (R)-2-Carbamoyl-pyrrolidine-1-carboxylic acid tert-butyl ester; N-Methylmorpholine (9.85 g, 97.5 mmol) and isobutyl chloroformate (13.3 g, 97.5 mmol) was added to (R)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (20.0 g, 92.9 mmol) in THF (200 mL) at -78° C. and stirred for 1 h. Ammonium hydroxide (58 mL) was added slowly as the reaction warmed up to RT and stirred for a further 2 h. The reaction mixture was partitioned between CH2Cl2 and water. The organic extracts were washed with 1 M HCl, dried over sodium sulphate, filtered and concentrated to afford the title product (10.8 g, 54percent) as a colourless semisolid.1H NMR (300 MHz, CDCl3): δ (ppm) 5.91-6.13 (m, 1H), 4.17-4.30 (m, 2H), 3.37-3.48 (m, 2H), 2.10-2.18 (m, 2H), 1.84-1.96 (m, 2H), 1.45 (s, 9H).
Reference: [1] Patent: US2007/259926, 2007, A1, . Location in patent: Page/Page column 9
[2] Tetrahedron, 2009, vol. 65, # 46, p. 9536 - 9541
  • 20
  • [ 37784-17-1 ]
  • [ 137496-71-0 ]
Reference: [1] Tetrahedron Letters, 1995, vol. 36, # 8, p. 1223 - 1226
  • 21
  • [ 37784-17-1 ]
  • [ 138108-72-2 ]
YieldReaction ConditionsOperation in experiment
96% With borane-THF In tetrahydrofuran at 0 - 20℃; for 4 h; Inert atmosphere 1-(tert-Butoxycarbonyl)-3(R)-pyrrolidinylmethanol
To a solution of 1-(tert-butoxycarbonyl)pyrrolidine-3(R)-carboxylic acid (800 mg, 3.72 mmol) in 20 mL of anhydrous THF was added dropwise BH3.THF complex (1M in THF, 7.4 mL, 2.0 equiv.) at 0° C. under N2.
The resulting solution was stirred for 4 h at room temperature.
The reaction was then quenched with water.
The mixture was concentrated under vacuum and extracted with EtOAc.
The combined organic layers were dried over Na2SO4 and concentrated in vacuo.
The residue was applied onto a silica gel column, which was eluted with EtOAc/petroleum ether 1:5 to give the title compound (720 mg, 96percent) as a colorless oil. LC-MS (ESI) m/z 202 (M+H+).
Reference: [1] Patent: US2013/184313, 2013, A1, . Location in patent: Paragraph 1653; 1654
  • 22
  • [ 37784-17-1 ]
  • [ 228244-04-0 ]
Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3524 - 3548
  • 23
  • [ 37784-17-1 ]
  • [ 101555-60-6 ]
Reference: [1] Helvetica Chimica Acta, 1999, vol. 82, # 10, p. 1539 - 1558
  • 24
  • [ 37784-17-1 ]
  • [ 783325-25-7 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 2009 - 2018
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