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[ CAS No. 37813-30-2 ]

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2D
Chemical Structure| 37813-30-2
Chemical Structure| 37813-30-2
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Product Details of [ 37813-30-2 ]

CAS No. :37813-30-2MDL No. :MFCD09264314
Formula : C12H21NO5 Boiling Point : -
Linear Structure Formula :-InChI Key :-
M.W :259.30Pubchem ID :12709318
Synonyms :

Computed Properties of [ 37813-30-2 ]

TPSA : 76.1 H-Bond Acceptor Count : 5
XLogP3 : 0.9 H-Bond Donor Count : 1
SP3 : 0.83 Rotatable Bond Count : 5

Safety of [ 37813-30-2 ]

Signal Word:WarningClassN/A
Precautionary Statements:P261-P305+P351+P338UN#:N/A
Hazard Statements:H302-H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 37813-30-2 ]

  • Upstream synthesis route of [ 37813-30-2 ]
  • Downstream synthetic route of [ 37813-30-2 ]

[ 37813-30-2 ] Synthesis Path-Upstream   1~11

  • 1
  • [ 24424-99-5 ]
  • [ 33996-30-4 ]
  • [ 37813-30-2 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine In ethanol; dichloromethane at 0 - 20℃; for 16.25 h; Step 2:To a solution of compound 2 (HCI salt, 146.2 g, 0.747 mol) dissolved in CH2CI2 (1600 ml) and EtOH (100 ml) and cooled to 0 0C was added Et3N (113.4 g, 1.12 mol, 156.2 ml). t-BOC anhydride (195.6, 0.90 mol) was added portion-wise. The reaction mixture was stirred at 0 0C for 15 min, then at RT for 16 h. The resulting mixture was concentrated to ~ 800 ml volume and washed with water. The organic solution was dried (MgSO4), filtered, and concentrated. Purification by silica gel chromatography (eluant: 20percent EtOAc - CH2CI2) gave the product 3 (193.7 g, 100percent) as a yellow oil. MS (M+Na): m/e 282. 1H-NMR (CDCI3) δ 1.30 (t, 3H)1 1.45 (s, 9H), 1.75 (m, 1 H), 2.10 (m, 1 H), 2.30 (m, 1 H), 3.45 and 3.55 (d, 1 H for two rotamers), 3.65 (dd, 1 H), 4.25 (m, 2H), 4.40 and 4.45 (t, 1H for two rotamers), 4.55 (broad s, 1 H).
100% With triethylamine In ethanol; dichloromethane at 0 - 20℃; Step 2:To a solution of compound 2 (HCl salt, 146.2 g, 0.747 mol) dissolved in CH2Cl2 (1600 ml) and EtOH (100 ml) and cooled to 0° C. was added Et3N (113.4 g, 1.12 mol, 156.2 ml). t-BOC anhydride (195.6, 0.90 mol) was added portionwise. The reaction mixture was stirred at 0° C. for 15 min, then at RT for 16 h. The resulting mixture was concentrated to 800 ml volume and washed with water. The organic solution was dried (MgSO4), filtered, and concentrated. Purification by silica gel chromatography (eluant: 20percent EtOAc-CH2Cl2) gave the product 3 (193.7 g, 100percent) as a yellow oil. MS (M+Na): m/e 282. 1H-NMR (CDCl3) δ 1.30 (t, 3H), 1.45 (s, 9H), 1.75 (m, 1H), 2.10 (m, 1H), 2.30 (m. 1H), 3.45 and 3.55 (d, 1H for two rotamers), 3.65 (dd, 1H), 4.25 (m, 2H), 4.40 and 4.45 (t, 1H for two rotamers), 4.55 (broad s, 1H).
100%
Stage #1: With triethylamine In 1,4-dioxane; water at 0℃; for 0.17 h;
Stage #2: at 20℃; for 20.00 h;
2B (13.4 g, 68.5 mmol) was dissolved in a mixed solution of 1,4-dioxane (50 mL) and water (50 mL) at room temperature and cooled to 0 ° C,Triethylamine (17.3 g, 0.171 mmol) was added and the mixture was stirred for 10 minutes.A mixture of di-tricarbonate (13.4 g, 68.5 mmol)In dichloromethane (50 mL) was added dropwise to the reaction solution and allowed to react at room temperature for 20 hours.Water (100 mL) was added to the reaction solution and extracted with dichloromethane (100 mL x 4).The organic phases were combined and washed with saturated brine solution (50 mL x 1). Dried over anhydrous magnesium sulfate,The filtrate was concentrated under reduced pressure to give pale yellow liquid 2C (18 g, yield 100percent).
Reference: [1] Patent: WO2008/8327, 2008, A2. Location in patent: Page/Page column 15-16
[2] Patent: US2011/3780, 2011, A1. Location in patent: Page/Page column 4
[3] Journal of Heterocyclic Chemistry, 2011, vol. 48, # 5, p. 1132 - 1139
[4] Patent: TW2017/8221, 2017, A. Location in patent: Page/Page column 38
[5] Synlett, 2011, # 14, p. 2059 - 2063
[6] Patent: WO2005/70934, 2005, A1. Location in patent: Page/Page column 59
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  • [ 61478-25-9 ]
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YieldReaction ConditionsOperation in experiment
74.9% With triethylamine In ethanol; dichloromethane at 0 - 20℃; Example 214. Synthesis of 3-fluoro-2-(4-(3-((2S,4R)-4-hydroxy-2- (hydroxymethyl)pyro-lidin-l-yl)-lH-pyrazol-l-yl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4- b]pyridin-2-yl)benzonitrile, 1-214 Synthesis of compound 214.2. To a solution of 214.1 (5.0 g, 25.6mmol, l.Oeq) in DCM (50 niL) and ethanol (10 niL) was added Et3N (5.2 niL, 0.038 mmol, 1.5 eq) di-tert.butyl dicarbonate (032mmol, 1.2eq) at 0 °C. Reaction mixture was stirred at room temperature for 16 h. Upon completion of the reaction, mixture was transferred into water and extracted with DCM, combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure to obtained crude which was purified by column chromatography to furnish 214.2 . (6.1 g, 74.9 percent). MS(ES): m/z 260.12 [M+H]+.
Reference: [1] Patent: WO2017/40757, 2017, A1. Location in patent: Paragraph 00954-00955
[2] Tetrahedron Asymmetry, 2002, vol. 13, # 2, p. 167 - 172
[3] Angewandte Chemie - International Edition, 2009, vol. 48, # 10, p. 1784 - 1787
  • 3
  • [ 13726-69-7 ]
  • [ 75-03-6 ]
  • [ 37813-30-2 ]
YieldReaction ConditionsOperation in experiment
91% With potassium carbonate In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 12.00 h; To a mixture of commercial (4R)-4-hydroxy-L-proline (75g, 0. 57MOL) in 10percent NAOH (11) was added (Boc) 20 (186g, 0. 855mol) at 0 C with stirring. The reaction was allowed to stir at RT for 10h and then washed with petroleum ether. The aqueous layer was acidified with citric acid to pH=4 and extracted with ethyl acetate. The combined organic layer was washed with brine and dried over NA2S04. The solvent was removed under vacuum to give crude (4R)-I-(TERT-BUTOXYCARBONYL)-4-HYDROXY-L-PROLINE (118G) as viscous liquid. Yield: 89percent To a solution of (4R)-1-(tert-butoxycarbonylo)-4-hydroxy-L-proline (100g, 0. 432MOL) in dry DMF (600ML), at 0 C was added K2CO3 (179g, 1. 3mol) followed by iodoethane (LOLG, 0. 65MOL). After stirring at RT for 12h, K2CO3 was filtered off and DMF was distilled off under reduce pressure. The residue was diluted with dichloromethane (11), washed with brine and dried. The solvent was removed under vacuum to give crude 1-1-TERT-BUTYL 2- ethyl (2S, 4R)-4-hydroxypyrrolidine-1, 2-dicarboxylate (103g) as yellow liquid. Yield: 91percent H NMR (300MHZ, CDC ) : 1.25 (t, 3H), 1.4 (d, 9H), 1.9-2. 2 (M, 2H), 2.5 (M, IH), 3.5 (M, 2H), 4.2 (M, 2H), 4.4-4. 6 (M, 2H). To a solution of 1-tert-butyl 2-ethyl (2S, 4R)-4-HYDROXYPYRROLIDINE-1, 2-dicarboxylate (100g, 0. 38MOL) in dry dichloromethane (1.51) at 25 C was added DMAP (47g, 0. 38MOL), followed by triethylamine (39g, 0. 38mol). To the above reaction mixture was added TBDMSCl (64g, 0. 42mol) dissolved in dry dichloromethane (200ML) drop-wise over a period OF 45MIN. After stirring at RT for 20H, the reaction mixture was diluted with water and separated the organic layer. The organic layer was washed with 5percent aq. citric acid, brine and dried over NA2SO4. The solvent was removed under vacuum to give I-TERT-BUTYL 2-ethyl (2S, 4R)-4- {[TERT-BUTYL (DIMETHYL) silyl] oxy} pyrrolidine-1, 2-DICARBOXYLATE (140g) as a colorless liquid. Yield: 97percent 'H NMR (300MHz, CDC13) : 0.0 (s, 6H), 0. 8 (s, 9H), 1.2 (t, 3H), 1. 45 (d, 9H), 1. 7-1. 9 (M, 2H), 2.2 (M, 1H), 3.3-3. 5 (M, 2H), 4.2 (M, 2H), 4.5 (M, 1H). To a suspension of lithium aluminium hydride (lOg) in dry tetrahydrofuran (750ml) at- 40 C was added 1-tert-butyl 2-ethyl 1-TERT-BUTYL 2-ethyl (2S,4R)-4-{[(tert- butyl (dimethyl) silyl] oxy} pyrrolidine-1, 2-dicarboxylate (100g, 0. 289mol) drop-wise in tetrahydrofuran (250ML). After stirring AT-TO C for 5H, the reaction mixture was quenched with 10percent NAOH (40ML). Filtered off the solid residue, washed with tetrahydrofuran and the filtrate was evaporated under reduce pressure to give tert-butyl (2S, 4R)-4-{[TERT- butyl (dimethyl) silyl] OXY}-2- (HYDROXYMETHYL) PYRROLIDINE-1-CARBOXYLATE (85g) as a colorless liquid. Yield: 94percent LCMS: ESI+: 232 (M-Boc+H)+, 276 (M-tBu+H) +, 354 (M+Na) + 'H NMR (300MHZ, DMSO-d6) : 0.05 (s, 6H), 0.78 (s, 9H), 1.33 (s, 9H), 1.65-2. 00 (m, 2H), 3.20 (m, 2H), 3. 38 (m, 2H), 3.70 (m, 1H), 4.30 (m, 1H), 4. 60 (t, 1H). To a mixture of DMSO (53g, 0. 68MOL) and oxalylchloride (43G, 0. 34MOL) in dry dichloromethane (1. 51) at-78oC was added tert-butyl (2S, 4R)-4-{[tert-butyl (dimethyl) silyl] OXY}-2-(HYDROXYMETHYL) PYLROLIDINE-L-CARBOXYLATE (75g, 0. 226MOL) drop-wise. After stirring at-78oC for IH, was added triethylamine (158ml, 1. 13MOL) drop-wise and warmed the reaction mixture slowly to RT. The reaction mixture was diluted with water and separated the organic layer. The organic layer was washed with brine and dried. The solvent was removed under vacuum to give tert-butyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl] OXY}-2-FORMYLPYRROLIDINE-L-CARBOXYLATE (70g) as pale yellow liquid. Yield: 94 percent
Reference: [1] Patent: WO2004/76407, 2004, A2. Location in patent: Page 27-29
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 9, p. 4030 - 4051
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Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1511 - 1514
[2] Patent: US2005/165065, 2005, A1. Location in patent: Page/Page column 21
  • 5
  • [ 1070-19-5 ]
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Reference: [1] Journal of Organic Chemistry, 1981, vol. 46, # 14, p. 2954 - 2960
  • 6
  • [ 41840-28-2 ]
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Reference: [1] Journal of Organic Chemistry, 1980, vol. 45, # 23, p. 4728 - 4739
  • 7
  • [ 74-96-4 ]
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Reference: [1] Chemistry Letters, 2006, vol. 35, # 3, p. 300 - 301
[2] Chemistry Letters, 2001, # 7, p. 634 - 635
  • 8
  • [ 64-17-5 ]
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  • [ 51-35-4 ]
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Reference: [1] Journal of Organic Chemistry, 2005, vol. 70, # 4, p. 1306 - 1315
  • 9
  • [ 51-35-4 ]
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Reference: [1] Chemistry Letters, 2006, vol. 35, # 3, p. 300 - 301
[2] Tetrahedron Asymmetry, 2002, vol. 13, # 2, p. 167 - 172
[3] Chemistry Letters, 2001, # 7, p. 634 - 635
[4] Journal of Organic Chemistry, 1981, vol. 46, # 14, p. 2954 - 2960
[5] Journal of Organic Chemistry, 1980, vol. 45, # 23, p. 4728 - 4739
[6] Journal of Heterocyclic Chemistry, 2011, vol. 48, # 5, p. 1132 - 1139
[7] Patent: TW2017/8221, 2017, A
[8] Journal of Medicinal Chemistry, 2018, vol. 61, # 9, p. 4030 - 4051
  • 10
  • [ 74-96-4 ]
  • [ 37813-30-2 ]
Reference: [1] Chemical Communications, 2004, # 10, p. 1208 - 1209
  • 11
  • [ 24424-99-5 ]
  • [ 37813-30-2 ]
Reference: [1] Chemistry Letters, 2001, # 7, p. 634 - 635
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 9, p. 4030 - 4051
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