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[ CAS No. 645-12-5 ] {[proInfo.proName]}

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Cat. No.: {[proInfo.prAm]}
Chemical Structure| 645-12-5
Chemical Structure| 645-12-5
Structure of 645-12-5 * Storage: {[proInfo.prStorage]}
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Quality Control of [ 645-12-5 ]

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Product Details of [ 645-12-5 ]

CAS No. :645-12-5 MDL No. :MFCD00003240
Formula : C5H3NO5 Boiling Point : -
Linear Structure Formula :- InChI Key :IODMEDPPCXSFLD-UHFFFAOYSA-N
M.W : 157.08 Pubchem ID :12577
Synonyms :

Calculated chemistry of [ 645-12-5 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.0
Num. rotatable bonds : 2
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 34.49
TPSA : 96.26 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) : -6.54 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.43
Log Po/w (XLOGP3) : 1.01
Log Po/w (WLOGP) : 0.89
Log Po/w (MLOGP) : -0.57
Log Po/w (SILICOS-IT) : -1.39
Consensus Log Po/w : 0.07

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.65
Solubility : 3.48 mg/ml ; 0.0222 mol/l
Class : Very soluble
Log S (Ali) : -2.62
Solubility : 0.376 mg/ml ; 0.00239 mol/l
Class : Soluble
Log S (SILICOS-IT) : -0.35
Solubility : 69.7 mg/ml ; 0.444 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.57

Safety of [ 645-12-5 ]

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

Application In Synthesis of [ 645-12-5 ]

* 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.

  • Downstream synthetic route of [ 645-12-5 ]

[ 645-12-5 ] Synthesis Path-Downstream   1~60

  • 2
  • [ 645-12-5 ]
  • [ 25084-14-4 ]
YieldReaction ConditionsOperation in experiment
100% With oxalyl dichloride; In dichloromethane; at 0 - 20℃; for 3h; To an ice cold solution of 5-nitrofuran-2- carboxylic acid (450 mg, 2.90 mmol) in DCM (10 ml) oxalyl chloride (2.50 L, 29 mmol) was added followed by addition of catalytic amount of DMF at 0 C and the reaction mixture was allowed to stir for 3h at room temperature. On completion, the solvent was evaporated under reduced pressure toobtain the acid chloride A with a quantitative yield (498 mg).
99% With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; for 4h; <strong>[645-12-5]5-Nitro-2-furoic acid</strong> (7a, 1.5 g, 9.4 mmol) was partly dissolved in 20 mL of dry dichloromethane. Oxayl chloride (1.8 mL, 21.3 mmol) was added followed by a few drops of DMF. The reaction was stirred for 4 hours then concentrated to dryness in vacuo to give intermediate acid chloride, 8a, as yellow oil which became solid upon standing, 1.0 g (99%). 5-Nitrofuran-2-carbonyl chloride (8a, 624 mg, 3.5 mmol) was dissolved in 10 mL of anhydrous dichloromethane and the solution was cooled to 0 C. 2-Aminophenol (9, 460 mg, 4.2 mmol) was added followed by Et3N (1.4 mL, 10.5 mmol) and the reaction was then allowed to warm to room temperature and stirred overnight. The reaction was concentrated to dryness in vacuo then diluted with EtOAc (75 mL) and washed with 0.5 N citric acid (2×), 10% sodium bicarbonate soln. (2×) and then satd. brine. The organic phase was dried over sodium sulfate and concentrated in vacuo to give a yellow film. The residual material was triturated with dichloromethane and upon cooling a yellow solid of N-(2-hydroxyphenyl)-5-nitrofuran-2-carboxamide, 10a, was collected, 631 mg (73%). HRMS calcd. for C11H8N2O5, 249.0511 found 249.0517. N-(2-Hydroxyphenyl)-5-nitrofuran-2-carboxamide (10a, 151 mg, 0.6 mmol) was dissolved in 6 mL of toluene containing p-toluenesulfonic acid, monohydrate (700 mg, 3.7 mmol) and the reaction was heated to reflux overnight. The reaction was concentrated in vacuo then purified through a silica gel column eluting with dichloromethane and increasing polarity to 10% EtOAc:dichloromethane to collect product 11a as a yellow-green solid, 62 mg (44%). 1H NMR (300 MHz, CDCl3) delta 7.87-7.81 (1H, m), 7.67-7.62 (1H, m), 7.46 (4H, m); HRMS calcd. for C11H6N2O4, 231.0406 found 231.0423. LC/MS Retention time 7.53 min (<95%), FABMS 231.3 (M+1).
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 4h; 5-Nitro-furan- 2-carboxylic acid (942 mg, 6 MMOL) in DCM (10 mL) was treated with oxalylchloride (1.046 mL, 12 MMOL) followed by 2 drops of DMF and stirred at room temperature for 4 hr. The reaction mix was concentrated in vacuum to obtain acid chloride.
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 4h; 5-NITRO-FURAN-2-CARBOXYLIC acid (942 mg, 6 MMOL) in DCM (10 mL) was treated with oxalylchloride (1.04 mL, 12 MMOL) followed by 2 drops of DMF and stirred at room temperature for 4 hrs. The reaction mix was concentrated in vacuum to obtain acid chloride and the crude was used in further reactions without purification and characterization.
General procedure: 5-Nitrothiophene-2-carboxylic acid (2.0g) was taken in a 100mL single neck RB flask equipped with N2-inlet, to this was added CH2Cl2 (30mL), OxallylChloride (6.0mL, 3V) at 0C and stirred for few minutes. Then DMF (few drops) was added slowly (drop wise) at same temperature until evolution of bubbles in the reaction mixture was stopped, and allowed to stir at room temperature for 3h. The reaction mixture was concentrated re-dissolved in dry CH2Cl2 and used in next step.
With thionyl chloride; for 1h;Reflux; A stirred mixture of 5-nitrofuroic acid (5-NFA 100mg; 0.64mmol) and SOCl2 (3mL) was refluxed in a silicone bath for 1h until gas evolution stops. The reaction mixture was left to take room temperature and, with the addition of anhydrous toluene (1mL), the excess of SOCl2 was evaporated in vacuo. Then, a solution of selected amine (0.86mmol in 0.5mL of anhydrous pyridine) was dropwise added to the acid chloride (obtained as oil) dissolved in anhydrous acetone (2.2mL) and the mixture was maintained at room temperature for 18-22h. The reaction mixture was diluted with EtOH, concentrated in vacuo and dried to give a residue which was purified by chromatographic column. Yield: 62-95%.

  • 3
  • [ 18638-99-8 ]
  • [ 645-12-5 ]
  • 5-nitro-furan-2-carboxylic acid 3,4,5-trimethoxy-benzylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-NITRO-2-FURAN carboxylic acid (300 rug, 1. 9 MMOL) and 3,4, 5-trimethoxy- benzylamine (326 muL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 532 mg of product (83% yield). TLC: Rf 0. 80 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDCI3) : No.3. 87 (3Hs, s), 3.89 (6Hs, s), 4. 58 (2HS, d, J = 5.8 Hz), 6.59 (2Hs, s), 6. 86-6. 93 (1 H, bs), 7.32 (1 H, d, J = 4.2 Hz), 7.4 (1H, d, J = 4.2 Hz); 13C NMR (300 MHz, CECI3) : 43. 42, 55.65, 60.28, 104. 85, 111. 88, 115.59, 132.13, 147. 42, 153.01, 155.59 ; Ei-Mass : 335.0 (M+-1, ;.
  • 4
  • [ 2217-40-5 ]
  • [ 645-12-5 ]
  • [ 37542-57-7 ]
YieldReaction ConditionsOperation in experiment
71% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2-furan carboxylic acid (300 mg, 1.9 mmol) and 1- amino (1, 2,3, 4-TETRAHYDRO) naphthalene (274 muL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) FOLLOWED by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 HR. at room temperature and worked up as explained in general procedure to afford 388 mg of product (71 % yield). TLC: RF 0. 75 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDCI3) : 61. 8-2.22 (4Hs, m), 2. 78-2. 98 (2Hs, m), 5.33-5. 45 (1 H, m), 6.81-6. 9 (1 H, bd, J = 8.3 Hz), 7.14- 7.27 (3Hs, m), 7.28 (1H, d, J = 3 HZ), 7.3 (1H, d, J = 4. 1 Hz), 7. 38 (1H, d, J = 4.1 Hz) ; 13C NMR (300 MHz, CECI3) : 19.41, 28.53, 29.48, 47.37, 111.90, 115.55, 125.58, 125.93, 126.46, 127.24, 128.12, 128.20, 128.44, 128. 90; El- Mass: 384.9 (M+-1).
  • 5
  • [ 372-19-0 ]
  • [ 645-12-5 ]
  • 5-nitro-furan-2-carboxylic acid (3-fluoro-phenyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro- 2-furan carboxylic acid (300 mg, 1.9 MMOL) and m-fluor aniline (184, UL, 1.9 mmol) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 429 mg product (89% yield). Rf 0. 82 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDC13) : ES6. 9-6. 98 (1 H, m), 7.33-7. 4 (2Hs, m), 7.44 (2Hs, q, J = 8. 8 Hz, 3. 8 Hz), 7.64-7. 7 (1 H, m), 8. 3-8. 4 (1 H, bs) ; 13G NMR (300 MHz, CDCl3) : 164.07, 160. 81, 153.44, 146.91, 137.35, 129.93, 116.55, 115. 16, 112. 09,107. 64; El-Mass : 248. 8 (M+-1).
  • 6
  • [ 645-12-5 ]
  • [ 20781-20-8 ]
  • 5-nitro-furan-2-carboxylic acid 2,4-dimethoxy-benzylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- NITRO-2-FURAN carboxylic acid (300 mg, 1.9 MMOL) and 2,4-dimethoxy- benzylamine (286 muL, 1.9 MMOL) in DMF (5mL) was treated with EDCI (730 mg, 3. 8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 508 mg of product (87% yield). TLC : Rf 0.50 (1: 1 hexane: ethyl acetate) ; H NMR (300 MHz, CECI3) : 63. 83 (3Hs, s), 3.91 (3Hs, s), 4.57 (2Hs, d, J = 5. 8 Hz), 6.45-6. 53 (2Hs, m), 7.02-7. 12 (1H, bs), 7.24 (1H, s), 7.27 (1H, d, J = 2. 5 Hz), 7.36 (1H, d, J = 2.5 Hz) ; 13C NMR (300 MHz, CDCI3) : 38.55, 54.88, 54.91, 98.19, 103.65, 111. 84, 115.14, 117.0, 130.23, 147.86, 155.35, 158.14, 160.40 ; Ei-Mass : 304. 8 (M+-1) ;
  • 7
  • [ 645-12-5 ]
  • [ 768-94-5 ]
  • 5-nitro-furan-2-carboxylic acid adamantan-1-ylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2- furan carboxylic acid (300 mg, 1. 9 MMOL) and ADAMANTYLAMINE (288 mg, 1. 9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 382 mg of product (69% yield). TLC : Rf 0.72 (1: 1 hexane: ethyl acetate) ; H NMR (300 MHz, CECI3,) : No.1. 70 (6Hs, s), 2.13 (9Hs, s), 6.18-6. 25 (1H, bs), 7.2 (1H, d, J = 3.7 Hz), 7.35 (1 H, d, J = 3.7 Hz) ; 13C NMR (300 MHz, CDCI3) : 28. 88, 35.65, 40.95, 52.62, 111.97, 114.78, 148.38, 154.58 ; EI-Mass : 288. 9 (M+-1).
  • 8
  • [ 645-12-5 ]
  • [ 2627-86-3 ]
  • 5-nitro-furan-2-carboxylic acid (1-(S)-phenyl-ethyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro- 2-furan carboxylic acid (300 mg, 1.9 MMOL) and 1-(S)-phenyl-ethylamine (245 , UL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 422 mg of product (85% yield). TLC: Rf 0. 75 (1: 1 hexane: ethyl acetate); 'H NMR (300 MHz, CDC13) : No.1. 65 (3Hs, d, J = 7.2 Hz), 5.32 (1 H, quin, J = 14.0 Hz, 7.2 Hz), 6.8-6, 92 (1 H, bd, J = 7. 2 Hz), 7.24-7. 45 (7Hs, m) ; 13C NMR (300 MHz, CDCl3) : 20.92, 48.69, 111. 92, 115.54, 125. 77,127. 31, 128. 33,141. 44, 147.52, 154. 84 ; EI-Mass : 258. 8 (M+-1).
  • 9
  • [ 645-12-5 ]
  • [ 34698-41-4 ]
  • [ 37542-55-5 ]
YieldReaction ConditionsOperation in experiment
80% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and 1-amino-indane (246 muL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure afford 415 mg of product (80% yield). TLC: Rf 0.75 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDC13) : ES1. 95-2.1 (1H, m), 2.62-2. 76 (1H, m), 2. 88-3. 02 (1H, m), 3.03-3. 17 (1 H, m), 5.67 (1 H, q, J 6.75 Hz, 13.5 Hz), 6. 88-6. 97 (1 H, bd, J = 6.75 Hz), 7.22- 7.39 (m6Hs, M) ; 13C NMR (300 MHz, CDCl3) : 29.77, 33.14, 54.36, 111.9, 115.53, 123.64, 124. 48, 126.45, 127.92, 141.42, 142. 98, 147. 51, 155.50 ; El- Mass: 370.9 (M+-1).
  • 10
  • [ 645-12-5 ]
  • [ 3886-69-9 ]
  • 5-nitro-furan-2-carboxylic acid (1-(R)-phenyl-ethyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro- 2-furan carboxylic acid (300 mg, 1.9 MMOL) and 1- (R)-phenyl-ethylamine (245 , uL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 422 mg of product (85% yield). TLC: Rf 0.75 (1: 1 hexane: ethyl acetate) ; 'H NMR (300 MHz, CDCl3) : ES1. 65 (3Hs, d, J = 7.2 Hz), 5.32 (1 H, quin, J = 14.0 Hz, 7. 2 Hz), 6. 8-6. 92 (1 H, bd, J = 7.2 Hz), 7.24-7. 45 (7Hs, M) ; 13C NMR (300 MHz, CDCl3) ; 20.91, 48. 69,111. 93,115. 54, 125. 77, 127. 31, 128. 32,141. 47, 147.53, 154. 87 ; El-Mass : 258. 8 (M+-1).
  • 11
  • [ 645-12-5 ]
  • [ 536-90-3 ]
  • 5-nitro-furan-2-carboxylic acid (3-methoxy-phenyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and m-anisidine (214 muL, 1.9 mmol) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 450 mg of product (90% yield). TLC: Rf 0.75 (1: 1 hexane: ethyl acetate) ; H NMR (300 MHz, CECI3) : D6. 79 (1H, ddd, J = 8.4 Hz, 2. 8 Hz, 1.2 Hz), 7.19 (1H, ddd, J = 8.4 Hz, 2.16 Hz, 0.7 Hz), 7.32 (1 H, t, J = 8.4 Hz), 7.39-7. 45 (2Hs, m), 8.22-8. 28 (1H, bs); 13C NMR (300 MHz, CDCl3) : 54.83, 105. 65, 110.83, 112.06, 112.13, 116.20, 129.39, 137.06, 147.35, 153.48, 159.71 ; EI-Mass : 260.8. (M+-1).
  • 12
  • [ 645-12-5 ]
  • [ 108-91-8 ]
  • [ 15182-30-6 ]
YieldReaction ConditionsOperation in experiment
71% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and cyclohexylamine (217 muL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 322 mg of product (71% yield). TLC: Rf 0.72 (1: 1 hexane: ethyl acetate) ; H NMR (300 MHz, CDCl3) : No.1. 15-1.5 (6Hs, m), 1.82 (2Hs, dt, J = 9.7 Hz, 2. 9 Hz), 2.03 (2 Hs, dd, J = 12. 3 Hz, 2. 6), 3.97 (1H, m), 6.42 (1H, bd, J = 6.2 Hz), 7.26 (1H, d, J = 3. 8 Hz), 7. 38 (1 H, d, J = 3.8 Hz) ; 13C NMR (300 MHz, CDCl3) : 23.25, 32.44, 33.06, 50.96, 111. 97, 115. 10, 147. 85, 115.28 ; EI-Mass : 261.1 (M++23).
  • 13
  • [ 645-12-5 ]
  • [ 104-94-9 ]
  • [ 14170-83-3 ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and p-anisidine (234 mg, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). THE REACTION mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 425 mg of product (85% yield). TLC: Rf 0.7 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDCI3) : D6. 95 (1 H, d, J = 8.9 Hz), 7. 38 (1 H, d, J = 3.9 Hz), 7.44 (1 H, d, J = 3.9 Hz), 7.6 (1H, d, J = 8.9 Hz), 8. 15-8. 21 (1H, bs) ; 13C NMR (300 MHz, CECI3) : 112.11, 113. 88, 115.94, 121.67, 128. 81,147. 55,153. 29,156. 78, 157. 1; EI-Mass : 260.9 (M+-1).
  • 14
  • [ 645-12-5 ]
  • [ 64-04-0 ]
  • 5-nitro-N-phenethylfuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and PHENETHYLAMINE (239, UL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure afford 402 mg of product (81% YIELD). TLC : Rf 0.70 (1: 1 hexane: ethyl acetate) ; 1H NMR (300 MHz, CDCl3) : No.2. 95 (2Hs, t, J = 7.5 Hz), 3.72 (2Hs, q, J = 13. 8 Hz, 7.5 Hz), 6. 81-6. 92 (1 H, bs), 7.21-7. 38 (7Hs, M) ; 13C NMR (300 MHz, CDC13) : 35.04, 40.29, 111. 8, 115.26, 126.3, 128. 17, 128. 28, 137. 58, 147.50, 155.68 ; El-Mass : 258. 8 (M+-1).
  • 15
  • [ 645-12-5 ]
  • [ 2393-23-9 ]
  • 5-nitro-furan-2-carboxylic acid 4-methoxy-benzylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro- 2-furan carboxylic acid (300 mg, 1.9 MMOL) and 4-methoxy benzylamine (248 , uL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 448 mg of product (85% yield). TLC: Rf 0.55 (1: 1 hexane: ethyl acetate); 'H NMR (300 MHz, CECI3) : No.3. 83 (3Hs, s), 4.58 (2Hs, d, J = 5.8 Hz), 6.82-6. 92 (1 H, bs), 6.92 (2Hs, d, J = 8 Hz), 7.27-7. 32 (3Hs, m), 7. 38 (1 H, d, J = 3.5 Hz); 13C NMR (300 MHz, CDCl3) : 42.57, 54. 78, 111. 87,113. 73,115. 49,128. 56, 128. 92,147. 51,155. 56,158. 85; EL-MASS : 275.6 (M+-1).
  • 16
  • [ 645-12-5 ]
  • [ 55-81-2 ]
  • 5-nitro-furan-2-carboxylic acid [2-(4-methoxy-phenyl)-ethyl]-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-NITRO-2-FURAN carboxylic acid (300 mg, 1.9 MMOL) and 4-methoxy- PHENETHYLAMINE (2799 UL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 443 mg of product (80% yield). TLC: Rf 0.6 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDCl3) : No.2. 9 (2Hs, t, J = 7.1 Hz), 3.68 (2Hs, q, J = 14.2 Hz, 7.1 Hz), 3.81 (3Hs, s), 6.67-6. 76 (1 H, bs), 6. 88 (2Hs, d, J=8. 6HZ), 7.16 (2Hs, d, J = 8. 6 Hz), 7.25 (1 H, d, J = 3. 8 Hz), 7.36 (1H, d, J = 3.8 Hz); 13C NMR (300 MHz, CECI3) : 34.12, 40.49, 54.73, 111.83, 113.69, 115.21, 129.12, 129.58, 147.58, 155.70, 157.97 ; El-Mass : 288.8 (M+-1).
  • 17
  • [ 645-12-5 ]
  • [ 5763-61-1 ]
  • 5-nitro-furan-2-carboxylic acid 3,4-dimetboxy-benzylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and 3,4-dimethoxy- BENZYLAMINE (289, UL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 526 mg of product (90% yield). TLC: Rf 0.3 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDCI3) : No.3. 9 (6Hs, s) 4.19 (2Hs, d, J = 6.5 Hz), 6.8-6. 97 (3Hs, m), 7.31 (1H, d, J = 3.4 Hz), 7.39 (1H, d, J 3.4 Hz); 13 C NMR (300 MHz, CDOS) : 42.91, 55.39, 55.40, 110. 85, 111.02, 111. 87, 115.46, 119.99, 129.11, 147.53, 148.31, 148. 73,155. 59; EI-Mass : 205.0 (M+- 1).
  • 18
  • [ 645-12-5 ]
  • [ 62-53-3 ]
  • [ 725-83-7 ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and aniline (152 muL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 376 mg of product (85% yield). TLC: Rf 0. 75 (1: 1 hexane: ethyl acetate) ; H NMR (300 MHz, CDC13) : 67. 24 (1 H, TT, J = 7.9 Hz, 0. 8 Hz), 7.39-7. 48 (4Hs, m), 7.7 (2H, dd, J = 8.4 Hz, 0. 8 Hz), 8. 22-8.28 (1K, bs); 13C NMR (300 MHz, CDCI3) : 112. 10,116. 21,119. 90, 125.03, 128. 73,135. 83,147. 34,153. 42; El-Mass : 230.8 (M+-1).
  • 19
  • [ 645-12-5 ]
  • [ 108-42-9 ]
  • [ 67764-28-7 ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and m-chloro aniline (202, UL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 432 mg product (85% yield). TLC: Rf 0.82 (1: hexane: ethyl acetate) ;'H NMR (300 MHz, CDCI3) : 67. 23 (1 H, ddd, J = 7.8 Hz, 2.0 Hz, 1.0 Hz), 7.35 (1 H, t, J = 7.8 Hz), 7.44 (2H, q, J=9. OHZ, 3. 8 HZ), 7.54 (1 H, ddd, J = 7. 8 Hz, 2. 0 HZ, 1. OHZ), 7.84 (1H, t, J = 2.0 Hz), 8.27-8. 33 (1H, bs); 13C NMR (300 MHz, CECI3) : 112.09, 116.58, 117. 85, 116. 58, 120.02, 125.10, 129.70, 134.45, 136.93, 146.88, 153.45 ; Ei-Mass : 265 (M+-1).
  • 20
  • [ 645-12-5 ]
  • [ 591-27-5 ]
  • [ 779327-08-1 ]
YieldReaction ConditionsOperation in experiment
70% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and 3-amino-phenol (208 mg, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 331 mg of product (70% yield). TLC: Rf 0.50 (1: 1 hexane: ethyl acetate) ; 1H NMR (500 MHz, CD30D) : E55. 09 (1 H, ddd, J = 8.0 Hz, 2.5 Hz, 1.0 Hz), 5.59 (1 H, ddd, J = 8. 0 Hz, 2. 0 Hz, 1.0 Hz), 5.64 (1 H, t, J = 8. 0 Hz), 5. 78 (1 H, t, J = 2.0 Hz), 5.9 (1 H, d, J = 4.0 Hz), 6. 45 (1 H, d, J = 4.0 Hz), 6.45 (1 H, s); EL-MASS : 247. 2 (M+- 1).
  • 21
  • [ 645-12-5 ]
  • [ 591-19-5 ]
  • 5-nitro-furan-2-carboxylic acid (3-bromo-phenyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and m-bromo aniline (306 uL, Attorney Docket No.: 1306/19/2/2 PCT 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 469 mg product (79% YIELD). TLC : Rf 0. 82 (1: 1 hexane: ethyl acetate); H NMR (300 MHz, CDC13) : CES7. 28 (1 H, t, J = 7.7 Hz), 7.36 (1 H, t, J =1.4 Hz), 7.43 (2H, q, T = 9. 6 HZ, 3. 8 HZ), 7.6 (1 H, ddd, J = 7. 7 Hz, 2.1 Hz, 1. 2 HZ), 7. 98 (1 H, t, J 2. 1 Hz), 8. 23-8. 3 (1 H, bs) ; 13C NMR (300 MHz, CDCl3) : 112.05, 116.54, 118. 39,122. 87, 127. 95,129. 95,137. 20,140. 72,146. 94,153. 50,158. 97; El-Mass : 310. 8 (M+- 1).
  • 22
  • [ 645-12-5 ]
  • [ 873-74-5 ]
  • C-176-18 [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro- 2-furan carboxylic acid (300 mg, 1.9 MMOL) and 4-amino benzonitrile (225 mg, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 mmol) followed by DMAP (582 mg, 4. 7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 441 mg of product (90% yield). TLC: Rf. 0.62 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDCl3) : No.7. 52 (1 H, d, J = 3.9 Hz), 7.61 (1 H, d, J = 3.9 Hz), 7.76 (1 H, d, J 8.9 Hz), 7. 98 (1H, d, J = 8.9 Hz); 13C NMR (300 MHz, CDCl3) : 106.23, 113.29, 117.24, 118.74, 120.51, 133.13, 142.09, 147.17, 151.84, 154.89 ; El-Mass : 255.8 (M+-1).
  • 23
  • [ 645-12-5 ]
  • [ 89-97-4 ]
  • N-(2-chlorobenzyl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2- furan carboxylic acid (300 mg, 1.9 MMOL) and 2-CHLORBENZYLAMINE (230, UL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 mmol) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 454 mg product (85% yield). TLC: Rf 0.72 (1: 1 hexane: ethyl acetate) ;'H NMR (300 MHz, CDC13) : No.4. 75 (2Hs, d, J = 6.2 Hz), 7.68-7. 09 (1 H, bs), 7.27-7. 32 (3Hs, m), 7.38 (1 H, d, J = 3.9 Hz), 7.41-7. 49 (2Hs, M) ; 13C NMR (300 MHz, CECI3) : 40.99, 111. 82,115. 64,126. 69,128. 91,129. 21,129. 87, 133.27, 133.90, 147. 28, 155.67 ; El-Mass : 278. 8 (M+-1).
  • 24
  • [ 645-12-5 ]
  • [ 617-89-0 ]
  • 5-nitro-furan-2-carboxylic acid (furan-2-ylmethyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5- Nitro-2-furan carboxylic acid (300 mg, 1.9 MMOL) and 2-aminomethyl furan (92 , uL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3. 8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 383 mg of product (85% yield). TLC: Rf 0. 68 (1: 1 hexane: ethyl acetate); 'H NMR (300 MHz, CDCl3) : No.4 : 67 (2Hs, d, J = 5.1 Hz, 3.0 Hz, 2.0 Hz, 0.4 Hz), 6.33-6. 4 (2H, m), 6. 86-6. 94 (1H, bs), 7.32 (1H, d, J = 3. 9 Hz), 7. 38 (1H, d, J = 3.9 Hz), 7.42 (1 H, dd, J = 2. 06 Hz, 0.4 Hz); 13C NMR (300 MHz, CECI3) : 35. 82, 107. 83, 110. 04, 111. 81, 115. 69,142. 14,147. 23,149. 36, 155.48, 160. 59; EI- Mass: 234.8 (M+-1)
  • 26
  • [ 645-12-5 ]
  • [ 15806-29-8 ]
  • 5-nitro-furan-2-carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 14h; 5-Nitro-2-furan carboxylic acid (300 mg, 1. 9 MMOL) and 2, 4- methoxy phenethylamine (319, uL, 1.9 MMOL) in DMF (5 mL) was treated with EDCI (730 mg, 3.8 MMOL) followed by DMAP (582 mg, 4.7 MMOL). The reaction mix was stirred for 14 hr. at room temperature and worked up as explained in general procedure to afford 550 mg of product (90% yield). TLC: Rf 0.75 (1: 1 hexane: ethyl acetate) ; 1H NMR (300 MHz, CDCI3) : D2. 89 (2Hs, t, J = 7.3 Hz), 3.69 (2Hs, q, J = 14.7 Hz, 7.3 Hz), 3.86 (3Hs, s), 3.88 (3Hs, s), 6.7-6. 87 (4Hs, m), 7.24 (1 H, d, J = 4 Hz), 7.35 (1 H, d, J = 4Hz) ; 13C NMR (300MHZ, CDC13) : 34.58, 40.39, 55.36, 55.41, 111.06, 111.37, 111.83, 115.23, 120.15, 130.10, 147.45, 147.55, 148.71, 155.68 ; Ei-Mass : 318.9 (M+-1).
  • 27
  • [ 645-12-5 ]
  • [ 898254-25-6 ]
  • C39H46N4O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 0.5h; HBTU (0.15 g, 0.40 mmol) and DIEA (0.1 mL, 0.80 mmol) were added to a solution of compound VI (0.2 g, 0.36 mmol) and 5-nitro-furan-2-carboxylic acid (62.8 mg, 0.40 mmol) in DMF (15 mL). After stirring for 30 minutes at 20 C. under Ar, the reaction was quenched by addition of brine (45 mL) and the mixture was extracted with EtOAc (4×30 mL). The organic layers were combined and washed sequentially with 1 M HCl (10 mL), a saturated NaHCO3 aqueous solution (10 mL), and a saturated NaCl aqueous solution (10 mL). The organic phase was then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product thus obtained was purified by flash chromatography to give compound 25 (0.23 g, 90%) as a white solid. LC-MS (M+H+): 699
  • 28
  • [ 934370-66-8 ]
  • [ 645-12-5 ]
  • 1-(9H-carbazol-4-yloxy)-3-{4-(5-nitro-2-furoyl)piperazin-1-yl}propan-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 12h; To a solution of <strong>[645-12-5]5-Nitrofuroic acid</strong> (1.56 g, 9.9 mmol) in DMF (30 niL) was added DIPEA (4.3 mL, 24.8 mmol), EDCI (3.18 g, 16.5 rnmol), HOBt (0.44 g, 3.3 mmol) followed by the l-(9H-carbazol-4-yloxy)-3-piperazin-l-ylpropan-2-ol (2.7 g, 8.3 mmol, prepared following the procedure described above in step II, example 26). The reaction mixture was stirred at room temperature for 12 hours and was diluted with DCM (100 mL), washed with water and brine solution. The organic layer was dried on anhydrous Na2SO4, concentrated and purified by silica gel column chromatography, using hexane/EtOAc (4:6) to afford the title compound as yellow colored solid (2.0 g, 51 % yield) with m.p: 178-181 0C. 1H NMR (400 MHz, DMSO): delta 2.30-2.60 (m, 4H), 2.67-2.69 (m, 2H), 3.63-3.69 (m, 4H), 4.13-4.21 (m, 3H), 5.08 (s, IH), 6.69 (d, IH, J = 8.0 Hz), 7.06 (d, IH, J= 8.0 Hz), 7.14 (t, IH, J= 8.0 Hz), 7.24-7.36 (m, 3H), 7.44 (d, IH, J= 8.0 Hz), 7.66 (d, IH, J= 4.0 Hz), 8.22 (d, IH, 8.0 Hz), and 11.25 (s, IH). MS m/z: 464.8 (M+l).
  • 29
  • [ 645-12-5 ]
  • [ 481-29-8 ]
  • [ 1182757-26-1 ]
YieldReaction ConditionsOperation in experiment
73.2% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 20℃; for 6.5h; The reaction mixture of <strong>[645-12-5]5-nitro-2-furoic acid</strong> (157 mg, 1.0 mmol), epiandrosterone (163 mg, 0.60 mmol), EDCI (200 mg, 1.05 mmol), DMAP (20 mg, 0.2 mmol) and THF (4 ml) was stirred at room temperature for 6.5 h. Evaporation of THF gave a residue which was dissolved in dichloromethane (20 ml). The organic layer of dichloromethane was washed with H2O, 5% Na2CO3, H2O and brine, and then dried over MgSO4. The solvent was removed under vacuum. The resulting solid was recrystallized from C2H5OH to give 180 mg (73.2%) (3beta,5alpha)-3-hydroxyandrostan-17-one 5-nitro-2-furoate 134 mg.The chemical structure analysis was performed by 1HNMR (CDCl3, 600 MHz): delta 7.35 (s, 1H, Ar-H), 7.28(s, 1H, Ar-H), 4.99 (s, 1H, H-3), 2.45 (t, 1H, H-16), 2.20-0.70 (m, 21H, ), 0.90 (s, 3H, CH3-19), 0.87 (s, 3H, CH3).
73.2% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 20℃; for 6.5h; [00156] 2. (3 , 5alpha) -3-Hydroxyandrostan-17-one-5-nitro-2-furoate (991027).; A mixture of <strong>[645-12-5]5-nitro-2-furoic acid</strong> (157 mg, 1.0 mmol), epiandrosterone (163 mg , 0.60 mmol), EDCI (200 mg, 1.05 mmol), DMAP (20 mg 0.2 mmol) and THF (4 mL) was stirred at ambient temperature for 6.5 h. After removing the solvent in vacuo, the resulting residue was dissolved in dichloromethane (20 mL) . The dichloromethane containing organic layer was washed sequentially with water, a 5% Na2C03 solution, and brine (20 mL) . After drying over MgS04, the solvent was removed in vacuo. The resulting solid was recrystallized from ethanol to give (3beta, 5alpha) -3-hydroxyandrostan- 17-one-5-nitro-2-furoate (180 mg; yield = 73.2 %) . 1HNMR (CDC13, 600 MHz): delta 7.35 (s, 1H, Ar-H), 7.28 (s, 1H Ar-H), 4.99 (s, 1H, H-3), 2.45 (t, 1H, H-16), 2.20-0.70 (m, 21H) , 0.90 (s, 3H, CH3-19), 0.87 (s, 3H, CH3) .
  • 30
  • [ 645-12-5 ]
  • [ 64-17-5 ]
  • [ 943-37-3 ]
YieldReaction ConditionsOperation in experiment
98% 5-Nitro-furan-2-carboxylic acid was stirred in dichloromethane (50ML), then oxalyl chloride (2.60g) and DMF (LML) were added. After 45 minutes, the reaction mixture was concentrated, and the resulting residue was stirred in CH2CL2 (50mL) at 0 C. After the solution was sufficiently cooled, EtOH (4mL) and triethylamine (4. 40ML) were added. After 15 minutes, the reaction mixture was warmed to room temperature and was allowed to stir for 1 hour. The reaction mixture was then washed with saturated NAHC03, water, and brine. The organic layer was dried over MGS04, filtered and the filtrate was concentrated at reduced pressure to afford the title compound (2.89g, 98%). 1H NMR (400MHZ, CDC13) : 7.33 (1H, d, J= 3. 9Hz), 7.26 (1H, d, J= 6. 8Hz), 4.44 (2H, t, J= 7. 1HZ), 1.41 (3H, q, J=7. 1HZ).
98% 5-Nitro-furan-2-carboxylic acid was stirred in dichloromethane (SOML), then oxalyl chloride (2.60g) and DMF (LML) were added. After 45 minutes, the reaction mixture was concentrated, and the resulting residue was stirred in CH2C12 (50mL) at 0 C. After the solution was sufficiently cooled, EtOH (4ML) and triethylamine (4. 40ML) were added. After 15 minutes, the reaction mixture was warmed to room temperature and was allowed to stir for 1 hour. The reaction mixture was then washed with saturated NAHC03, water, and brine. The organic layer was dried over MGS04, filtered and the filtrate was concentrated at reduced pressure to afford the title compound (2. 89G, 98%). 1H NMR (400MHZ, CDC13): 7.33 (1H, d, J= 3. 9Hz), 7.26 (1H, d, J= 6. 8HZ), 4.44 (2H, t, J= 7. 1HZ), 1.41 (3H, q, J=7. 1HZ)
89% With graphene oxide; at 100℃; for 24h; General procedure: A mixture of acid (0.2 mmol), alcohol (0.6 mmol) and GO (50 wt%, calculated with the mass of acid) in ethyl alcohol or DCE (1 mL) was placed in a test tube equipped with a magnetic stirring bar. The mixture was stirred at 100 C for 24 h. After the reaction was finished, filtered the GO, solvent was removed, and the residue was separated by column chromatography to give the pure sample.
  • 31
  • [ 645-12-5 ]
  • [ 213596-33-9 ]
  • [ 1262967-29-2 ]
  • 32
  • [ 645-12-5 ]
  • [ 2493-04-1 ]
YieldReaction ConditionsOperation in experiment
93% General procedure: To a solution of carboxylic acid (10 mmol) in THF (10 mL), DIPEA (11 mmol, 1.42 mL) and 50% T3P in EtOAc (20 mmol, 6.36 mL) were added at 0 C and the solution was stirred for about 10 min. Then aqueous solution of NaBH4 (10 mmol, 388 mg in 0.3 mL of H2O) was added to the reaction mixture at the same temperature and the reaction was allowed to stir till the completion of the reaction as indicated by TLC. After the completion of the reaction, the solvent was evaporated and the crude alcohol was extracted into EtOAc and the organic phase was washed with 5% citric acid (10 mL × 2), 5% Na2CO3 (10 mL × 2), water, and brine solution. The product was isolated after the evaporation of solvent under reduced pressure and dried over anhydrous Na2SO4.
  • 33
  • [ 645-12-5 ]
  • [ 1445869-23-7 ]
  • [ 1445868-89-2 ]
YieldReaction ConditionsOperation in experiment
81% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h;Reflux; To a stirred solution of 4-fluoro nitrobenzene (la, 3.1 g, 22 mmol) and methyl 4-piperidine carboxylate (2, 3.15 g, 22 mmol) in DMF solvent and K2CO3 (7.6 g, 55 mmol) as base and heated at 80 C for 10h, after completion of the reaction, reaction is poured into ice water and extracted into ethyl acetate finally purification by column chromatography to afford pure compound methyl 1-(4-nitrophenyl)-4-piperidinecarboxylate (3a, 4.93 g, 85%). To a stirred solution of ester (3a, 4.75 g, 18 mmol) in ethanol, NH2NH2. H2O (2.25 g, 45 mmol) is added and refluxed for 24h. After completion of the reaction ethanol is evaporated under vaccum and water is added and extracted into ethyl acetate finally purification by column chromatography to afford pure compound 1-(4- nitrophenyl)-4-piperidinecarbohydrazide (4a, 3.99 g, 84%). Addition N,N-dimethyl carbamyl chloride (1.29 g, 12 mmol) to hydrazide (4a, 3.17 g, 12 mmol) in pyridine at room temperature (27 C) and fallowed by reflux at temperature 85 C for 2.5h. After completion of the reaction, the reaction mixture is cooled and filtered. The residue is recrystallized from water to get 5-[1 -(4-nitrophenyl)-4-piperidyl]-2,3-dihydro- 1,3,4- oxadiazol-2-one (Sa, 1.39 g, 40%). Nitro compound (5a, 1.16 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4- aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7a, 884 mg, 85%). To a stirred solution of 5-nitro2-furanoic acid (0.16 g, 1 mmol) in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide)) (0.19 g, 1 mmol) and amine compound (7a, 0.26 g, 1 mmol) and stirred for 2h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to affordpure compound N2-4-[4-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8a, 323 mg, 81%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.97 (m, 2H), 2.05-2.13 (m, 2H), 2.67-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 6.92 (d, 2H, J= 9.06 Hz), 7.34 (d, 1H, J=3.77 Hz), 7.38 (d, 1H, J= 3.77 Hz), 7.53 (d, 1H, J=9.06 Hz), 8.23 (bs, 1H); MS (ESI): m/z (400) (M+1)+.
81% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; To a stirred solution of 4-fluoro nitrobenzene (1a, 3.1 g, 22 mmol) and methyl 4-piperidine carboxylate (2, 3.15 g, 22 mmol) in DMF solvent and K2CO3 (7.6 g, 55 mmol) as base and heated at 80 C. for 10 h, after completion of the reaction, reaction is poured into ice water and extracted into ethyl acetate finally purification by column chromatography to afford pure compound methyl 1-(4-nitrophenyl)-4-piperidinecarboxy- late (3a, 4.93 g, 85%). To a stirred solution of ester (3a, 4.75 g, 18 mmol) in ethanol, NH2NH2. H2O (2.25 g, 45 mmol) is added and refluxed for 24 h. After completion of the reaction ethanol is evaporated under vaccum and water is added and extracted into ethyl acetate finally purification by column chromatography to afford pure compound 1-(4-nitrophenyl)-4-piperidinecarbohydrazide (4a, 3.99 g, 84%). Addition N,N-dimethyl carbamyl chloride (1.29 g, 12 mmol) to hydrazide (4a, 3.17 g, 12 mmol) in pyridine at room temperature (27 C.) and fallowed by reflux at temperature 85 C. for 2.5 h. After completion of the reaction, the reaction mixture is cooled and filtered. The residue is recrystallized from water to get 5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a, 1.39 g, 40%). Nitro compound (5a, 1.16 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4 h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7a, 884 mg, 85%). To a stirred solution of 5-nitro2-furanoic acid (0.16 g, 1 mmol) in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide)) (0.19 g, 1 mmol) and amine compound (7a, 0.26 g, 1 mmol) and stirred for 2 h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(5-oxo-4,5-dihydro -1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8a, 323 mg, 81%). NMR (CDCl3, 300 MHz): 1.84-1.97 (m, 2H), 2.05-2.13 (m, 2H), 2.67-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 6.92 (d, 2H, J=9.06 Hz), 7.34 (d, 1H, J=3.77 Hz), 7.38 (d, 1H, J=3.77 Hz), 7.53 (d, 1H, J=9.06 Hz), 8.23 (bs, 1H); MS (ESI): m/z (400) (M+1)+.
  • 34
  • [ 645-12-5 ]
  • [ 1445869-25-9 ]
  • [ 1445868-90-5 ]
YieldReaction ConditionsOperation in experiment
85% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(4-Nitrophenyl)-4-piperidyl]-2,3 -dihydro- 1,3 ,4-oxadiazol-2-one (5a, 1.16 g, 4 mmol) on reacting with CH3I (0.68g. 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at 27 C for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-methyl-5-[1-(4-nitrophenyl)-4-piperidyl]- 2,3-dihydro-1,3,4-oxadiazol-2-one (6a, 1.10 g, 91%). Nitro compound (6a, 1.21 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65C for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified insilica column (60-120) to afforded pure compound 5 -[1 -(4-aminophenyl)-4-piperidyl}-3 -methyl-2,3-dihydro- 1,3 ,4-oxadiazol-2- one (7b, 960 mg, 88%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylamino propyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7b, 0.27g. 1 mmol) and stirred for 2h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as? eluant to afford pure compound N2-4-[4-(4-methyl-5-oxo-4,5-dihydro- 1 ,3,4-oxadiazol-2-yl)piperidinojphenyl- 5-nitro-2-furamide (8b, 351 mg, 85%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.97 (m, 2H), 2.05-2.13 (m, 2H), 2.67-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 3.87 (s, 3H), 6.91 (d, 2H, J= 9.06 Hz), 7.35 (d, 1H, J= 3.77 Hz), 7.38 (d, 1H, J= 3.77 Hz), 7.50 (d, 1H, J= 9.06 Hz), 8.20 (bs, 1H); MS (ESI): m/z (414) (M+1)+.
85% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(4-Nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a, 1.16 g, 4 mmol) on reacting with CH3I (0.68g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at 27 C. for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-methyl-5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6a, 1.10 g, 91%). Nitro compound (6a, 1.21 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-3 -methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7b, 960 mg, 88%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylamino propyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7b, 0.27 g, 1 mmol) and stirred for 2 h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8b, 351 mg, 85%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.97 (m, 2H), 2.05-2.13 (m, 2H), 2.67-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 3.87 (s, 3H), 6.91 (d, 2H, J=9.06 Hz), 7.35 (d, 1H, J=3.77 Hz), 7.38 (d, 1H, J=3.77 Hz), 7.50 (d, 1H, J=9.06 Hz), 8.20 (bs, 1H); MS (ESI): m/z (414) (M+1)+.
  • 35
  • [ 645-12-5 ]
  • [ 1445869-27-1 ]
  • [ 1445868-91-6 ]
YieldReaction ConditionsOperation in experiment
86% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a, 1.16 g, 4 mmol) on reacting with C2H5Br (0.53 g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-ethyl-5-[1-(4-nitro phenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6b, 1.17 g, 92%). Nitro compound (6b, 1.27 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-3-ethyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7c, 1.02 g, 89%). To a stirred solution of 5-nitro2- furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1- Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7c, 0.29g, 1 mmol) and stirred for 2h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-ethyl-5-oxo-4,5-dihydro- 1 ,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8c, 367 mg, 86%). 1H (CDCl3, 300 MHz): delta 1.34 (t, 3H, J 7.55 Hz), 1.85-1.99 (m, 2H), 2.07-2.13 (m, 2H), 2.67-2.77 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 3.70-3.78 (m, 2H), 6.92 (d, 2H, J= 9.06 Hz), 7.33 (d, 1H, J= 3.77 Hz), 7.38 (d, 1H, J= 3.77 Hz), 7.53 (d, 1H, J=9.06 Hz), 8.20 (bs, 1H); MS (ESI): m/z (450) (M+23)+.
86% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(4-Nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a, 1.16 g, 4 mmol) on reacting with C2H5Br (0.53 g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C.) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-ethyl-5-[1-(4-nitro phenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6b, 1.17 g, 92%). Nitro compound (6b, 1.27 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-3-ethyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7c, 1.02 g, 89%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7c, 0.29g, 1 mmol) and stirred for 2h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-ethyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperi dino]phenyl-5-nitro-2-furamide (8c, 367 mg, 86%). 1H NMR (CDCl3, 300 MHz): delta 1.34 (t, 3H, J=7.55 Hz), 1.85-1.99 (m, 2H), 2.07-2.13 (m, 2H), 2.67-2.77 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 3.70-3.78 (m, 2H), 6.92 (d, 2H, J=9.06 Hz), 7.33 (d, 1H, J=3.77 Hz), 7.38 (d, 1H, J=3.77 Hz), 7.53 (d, 1H, J=9.06 Hz), 8.20 (bs, 1H); MS (ESI): m/z (450) (M+23)+.
  • 36
  • [ 645-12-5 ]
  • [ 1445869-29-3 ]
  • [ 1445868-92-7 ]
YieldReaction ConditionsOperation in experiment
83% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a 1.16 g, 4 mmol) on reacting with C6H5CH2Br (0.82 g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-benzyl-5-[1-(4- nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6c, 1.42 g, 94%). Nitro compound (6c, 1.52 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-3-benzyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7d, 1.23 g, 88%). To a stirred solution of 5-nitro2- furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7d, 0.35 g, 1 mmol) and stirred for 2h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-benzyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2- yl)piperidino]phenyl-5-nitro-2-furamide (8d, 405 mg, 83%). 1H NMR (CDCl3, 300 MHz): delta 1.83-1.97 (m, 2H), 2.05-2.11 (m, 2H), 2.65-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.62-3.69 (m, 2H), 6.91 (d, 2H, J = 9.06 Hz), 7.28-7.34 (m, 5H),7.35 (d, 1H, J = 3.77 Hz), 7.38 (d, 1H, J = 3.77 Hz), 7.50 (d, 1H, J 9.06 Hz), 8.19 (bs, 1H); MS (ESI): m/z (490) (M+1)+.
83% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(4-Nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a 1.16 g, 4 mmol) on reacting with C6H5CH2Br (0.82 g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C.) for 10h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-benzyl-5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6c, 1.42 g, 94%). Nitro compound (6c, 1.52 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4 h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-3-benzyl -2,3-dihydro-1,3,4-oxadiazol-2-one (7d, 1.23 g, 88%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7d, 0.35 g, 1 mmol) and stirred for 2 h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-benzyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8d, 405 mg, 83%). 1H NMR (CDCl3, 300 MHz): delta 1.83-1.97 (m, 2H), 2.05-2.11 (m, 2H), 2.65-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.62-3.69 (m, 2H), 6.91 (d, 2H, J=9.06 Hz), 7.28-7.34 (m, 5H), 7.35 (d, 1H, J=3.77 Hz), 7.38 (d, 1H, J=3.77 Hz), 7.50 (d, 1H, J=9.06 Hz), 8.19 (bs, 1H); MS (ESI): m/z (490) (M+1)+.
  • 37
  • [ 645-12-5 ]
  • [ 1445869-32-8 ]
  • [ 1445868-93-8 ]
YieldReaction ConditionsOperation in experiment
80% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h;Reflux; To a stirred solution of 3,4-difluoro nitrobenzene (1b, 3.5 g, 22 mmol) and methyl 4-piperidine carboxylate (2, 3.15 g, 22 mmol) in DMF solvent and K2CO3 (7.6 g, 55 mmol) as base and heated at 80 C for 10 h, after completion of the reaction, reaction is poured into ice water and extracted into ethyl acetate finally purification by column chromatography to afford pure compound methyl 1-(2-fluoro-4-nitrophenyl)-4-piperidine carboxylate (3b, 5.33 g, 86%). To a stirred solution of ester (3b, 5.0 g, 18 mmol) in ethanol, NH2NH2.H2O (2.25 g, 45 mmol) is added and refluxed for 12h. After completion of the reaction ethanol is evaporated under vaccum and water is added and extracted into ethyl acetate finally purification by column chromatography to afford pure compound 1-(2-fluoro-4-nitro phenyl)-4-piperidinecarbohydrazide (4b, 4.62 g, 91%). Addition N,Ndimethyl carbamyl chloride (1.29 g, 12 mmol) to hydrazide (4b, 3.38 g, 12 mmol) in pyridine at room temperature (27 C) and fallowed by reflux at temperature 85 C for 2.5h. After completion of the reaction, the reaction mixture is cooled and filtered. The residue is recrystallized from water to get 5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5b, 1.47 g, 40%). Nitro compound (5b, 1.23 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7e, 920 mg, 83%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, I mmol) and amine compound (7e, 0.28 g, 1 mmol) and stirred for 2h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-3-fluoro-4-[4-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8e, 333 mg, 80%). 1H NMR (CDCl3, 300 MHz): delta 1.85-1.99 (m, 2H), 2.06-2.11 (m, 2H), 2.67-2.77 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69(m, 2H), 6.95 (t, 1H, J= 9.06 Hz), 7.27 (dd, 1H, J=1.55, 7.55 Hz), 7.38 (d, 1H, J= 3.77 Hz), 7.41 (d, 1H, J= 3.77 Hz), 7.56 (dd, 1H, J=2.26, 11.25 Hz), 8.30 (bs, 1H); MS (ESI): m/z (418) (M+1)+.
80% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; To a stirred solution of 3,4-difluoro nitrobenzene (1b, 3.5 g, 22 mmol) and methyl 4-piperidine carboxylate (2, 3.15 g, 22 mmol) in DMF solvent and K2CO3 (7.6 g, 55 mmol) as base and heated at 80 C. for 10h, after completion of the reaction, reaction is poured into ice water and extracted into ethyl acetate finally purification by column chromatography to afford pure compound methyl 1-(2-fluoro-4-nitrophenyl)-4-piperidine carboxylate (3b, 5.33 g, 86%). To a stirred solution of ester (3b, 5.0 g, 18 mmol) in ethanol, NH2NH2.H2O (2.25 g, 45 mmol) is added and refluxed for 12 h. After completion of the reaction ethanol is evaporated under vaccum and water is added and extracted into ethyl acetate finally purification by column chromatography to afford pure compound 1-(2-fluoro-4-nitro phenyl)-4-piperidinecarbohydrazide (4b, 4.62 g, 91%). Addition N,N-dimethyl carbamyl chloride (1.29 g, 12 mmol) to hydrazide (4b, 3.38 g, 12 mmol) in pyridine at room temperature (27 C.) and fallowed by reflux at temperature 85 C. for 2.5 h. After completion of the reaction, the reaction mixture is cooled and filtered. The residue is recrystallized from water to get 5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5b, 1.47 g, 40%). Nitro compound (5b, 1.23 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4 h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-2,3-dihydro-1,3 ,4-oxadiazol-2-one (7e, 920 mg, 83%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7e, 0.28 g, 1 mmol) and stirred for 2 h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-3-fluoro-4-[4-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8e, 333 mg, 80%). NMR (CDCl3, 300 MHz): delta 1.85-1.99 (m, 2H), 2.06-2.11 (m, 2H), 2.67-2.77 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 6.95 (t, 1H, J=9.06 Hz), 7.27 (dd, 1H, J=1.55, 7.55 Hz), 7.38 (d, 1H, J=3.77 Hz), 7.41 (d, 1H, J=3.77 Hz), 7.56 (dd, 1H, J=2.26, 11.25 Hz), 8.30 (bs, 1H); MS (ESI): m/z (418) (M+1)+.
  • 38
  • [ 645-12-5 ]
  • [ 1445869-34-0 ]
  • [ 1445868-94-9 ]
YieldReaction ConditionsOperation in experiment
87% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1 ,3,4-oxadiazol-2-one (5b, 1.23 g, 4 mmol) on reacting with CH3I (0.68 g, 4.8 mmol) in DMF in the presence of base K2C03 (1.38 g, 10 mmol) at 0 C for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 5-[1-(2-fluoro-4-nitrophenyl)-4- piperidyl]-3-methyl-2,3-dihydro-1 ,3,4-oxadiazol-2-one (6d, 1.18 g, 92%). Nitro compound (6d, 1.29 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7f, 920 mg, 83%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7f, 0.29 g, 1 mmol) and stirred for 2h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-3-fluoro-4-[4-(4-methyl-5-oxo-4,5-dihydro- 1 ,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8f, 375 mg, 87%). 1H NMR (CDCl3, 300 MHz): delta 1.84-1.97 (m, 2H), 2.05-2.13 (m, 2H), 2.67-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 3.87 (s, 3H), 6.94 (t, 1H, J=9.06 Hz), 7.27 (dd, 1H, J= 1.51, 7.55 Hz), 7.38 (d, 1H, J= 3.77 Hz), 7.44 (d, 1H, J= 3.77 Hz), 7.58 (dd, 1H, J= 2.25, 13.59 Hz), 8.33 (bs, 1H); MS (ESI): m/z (454) (M+23)+.
87% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadazol-2-one (5b, 1.23 g, 4 mmol) on reacting with CH3I (0.68 g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at 0 C. for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (6d, 1.18 g, 92%). Nitro compound (6d, 1.29 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4 h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5[1-(4-amino-2-fluorophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7f, 920 mg, 83%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7f, 0.29 g, 1 mmol) and stirred for 2 h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-3-fluoro-4-[4-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8f, 375 mg, 87%). 1 H NMR (CDCl3, 300 MHz): delta 1.84-1.97 (m, 2H), 2.05-2.13 (m, 2H), 2.67-2.75 (m, 1H), 2.82-2.91 (m, 2H), 3.64-3.69 (m, 2H), 3.87 (s, 3H), 6.94 (t, 1H, J=9.06 Hz), 7.27 (dd, 1H, J=1.51, 7.55 Hz), 7.38 (d, 1H, J=3.77 Hz), 7.44 (d, 1H, J=3.77 Hz), 7.58 (dd, 1H, J=2.25, 13.59 Hz), 8.33 (bs, 1H); MS (ESI): m/z (454) (M+23)+.
  • 39
  • [ 645-12-5 ]
  • [ 1445869-36-2 ]
  • [ 1445868-95-0 ]
YieldReaction ConditionsOperation in experiment
88% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro- 1 ,3,4-oxadiazol-2-one (5b, 1.23 g, 4 mmol) on reacting with C2H5Br (0.53 g, 4.8 mmol) in DMF in the presehce of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-ethyl-5-[1-(2-fluoro- 4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6e, 1.27 g, 95%). Nitro compound (6e, 1.34 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C for 4 h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution, is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]- 3-ethyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7g, 1.05 g, 86%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzo triazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7g, 0.3 g, 1 mmol) and stirred for 2 h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-ethyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]-3-fluorophenyl-5-nitro-2-furamide (8g, 391 mg, 88%). 1H NMR (CDCl3, 300 MHz): delta 1.34 (t, 3H, J= 7.55 Hz), 1.96-2.05 (m, 2H), 2.06-2.14(m, 2H), 2.68-2.75 (m, 1H), 2.77-2.86 (m, 2H), 3.43-3.50 (m, 2H), 3.72-3.79 (m, 2H),6.96 (t, 1H, J= 9.06 Hz), 7.28 (dd, 1H, J= 1.51, 7.55 Hz), 7.37 (d, 1H, J= 3.77 Hz), 7.42(d, 1H, J= 3.77 Hz), 7.58 (dd, 1H, J= 2.26, 13.59 Hz), 8.32 (bs, 1H); MS (ESI): m/z (446) (M+1)+.
88% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5b, 1.23 g, 4 mmol) on reacting with C2H5Br (0.53 g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C.) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-ethyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6e, 1.27 g, 95%). Nitro compound (6e, 1.34 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution, is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-3-ethyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7 g, 1.05 g, 86%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzo triazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7g, 0.3 g, 1 mmol) and stirred for 2 h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-ethyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]-3-fluorophenyl-5-nitro-2-furamide (8 g, 391 mg, 88%). 1H NMR (CDCl3, 300 MHz): delta 1.34 (t, 3H, J=7.55 Hz), 1.96-2.05 (m, 2H), 2.06-2.14 (m, 2H), 2.68-2.75 (m, 1H), 2.77-2.86 (m, 2H), 3.43-3.50 (m, 2H), 3.72-3.79 (m, 2H), 6.96 (t, 1H, J=9.06 Hz), 7.28 (dd, 1H, J=1.51, 7.55 Hz), 7.37 (d, 1H, J=3.77 Hz), 7.42 (d, 1H, J=3.77 Hz), 7.58 (dd, 1H, J=2.26, 13.59 Hz), 8.32 (bs, 1H); MS (ESI): m/z (446) (M+1)+.
  • 40
  • [ 645-12-5 ]
  • [ 1445869-38-4 ]
  • [ 1445868-96-1 ]
YieldReaction ConditionsOperation in experiment
85% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5b, 1.23 g, 4 mmol) on reacting with C6H5CH2Br (0.82 g, 1 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-benzyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6f, 1.52 g, 96%). Nitro compound (6f, 1.59 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C for 4h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]- 3-benzyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7h, 1.26 g, 86%). To a stirred solution of 5-nitro 2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethyl aminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7h, 0.36 g, 1 mmol) and stirred for 2h at room temperature (27 C), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-benzyl-5-oxo-4,5-dihydro-1,3,4- oxadiazol-2-yl)piperidino]-3-fluorophenyl-5-nitro-2-furamide (8h, 430 mg, 85%). 1H NMR (CDCl3, 300 MHz): delta 1.89-2.00 (m, 2H), 2.02-2.11 (m, 2H), 2.65-2.72 (m, 1H), 2.73-2.82 (m, 2H), 3.42-3.46 (m, 2H), 4.83 (s, 2H), 6.92 (t, 1H, J= 9.06 Hz), 7.25 (d, 2H, J= 7.55 Hz), 7.30-7.39 (m, 5H), 7.39 (d, 1H, J= 3.77 Hz), 7.55 (dd, 1H, J= 2.26, 13.59 Hz); MS (ESI):<BOLD> </BOLD>m/z (508) (M+1)+.
85% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 27℃; for 2h; 5-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3 ,4-oxadiazo 1-2-one (5b, 1.23 g, 4 mmol) on reacting with C6H5CH2Br (0.82 g, 1 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27 C.) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-benzyl-5-[1-(2-fluoro-4-nitrophenyl) -4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6f, 1.52 g, 96%). Nitro compound (6f, 1.59 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65 C. for 4 h, after completion of reaction methanol is evaporated under vaccum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-amino-2-fluorophenyl)-4-piperidyl]-3-benzyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7 h, 1.26 g, 86%). To a stirred solution of 5-nitro2-furanoic acid in DMF add. HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethyl aminopropyl) carbodi imide)) (0.19 g, 1 mmol) and amine compound (7 h, 0.36 g, 1 mmol) and stirred for 2 h at room temperature (27 C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(4-benzyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperi dino]-3-fluorophenyl-5-nitro-2-furamide (8 h, 430 mg, 85%). 1 H NMR (CDCl3, 300 MHz): delta 1.89-2.00 (m, 2H), 2.02-2.11 (m, 2H), 2.65-2.72 (m, 1H), 2.73-2.82 (m, 2H), 3.42-3.46 (m, 2H), 4.83 (s, 2H), 6.92 (t, 1H, J=9.06 Hz), 7.25 (d, 2H, J=7.55 Hz), 7.30-7.39 (m, 5H), 7.39 (d, 1H, J=3.77 Hz), 7.55 (dd, 1H, J=2.26, 13.59 Hz); MS (ESI): m/z (508) (M+1)+.
  • 41
  • [ 645-12-5 ]
  • 1-benzyl-5-((triphenylphosphoranylidene)methyl)-1H-tetrazole [ No CAS ]
  • 2-(1-benzyl-1H-tetrazol-5-yl)-1-(5-nitrofuran-2-yl)-2-(triphenylphosphoranylidene)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; at 20℃; for 12h;Cooling with ice; Compound 6c was prepared by an analogous method to that described in the literature [34]. A solution of phosphorus ylide 5 (2.1 mmol) and 5-nitrofuran-2-carboxylic acid (2.5 mmol) in dry CHCl3 (40 mL) was cooled in an ice bath. Then EDCI (3.2 mmol) and DMAP (catalytic) was added to it. After the addition, the mixture was stirred at room temperature for 12 h. The reaction mixture was washed with H2O (3 50 mL), dried and evaporated. The crude product was purified by flash chromatography (ethyl acetate). Ylide 6c was obtained as a yellow solid (4.59 g, 80%). m.p. > 210 C (decomp., from ethyl acetate/ hexane); IR (KBr) 515, 525, 688, 1099, 1300, 1541 cm-1; 1H-NMR (CDCl3) delta (ppm) 5.38 (d, J = 14.8 Hz, 1H), 5.49 (d, J = 14.8 Hz, 1H), 6.60 (d, J = 4.0 Hz, 1H), 6.80 (d, J = 4.0 Hz, 1H), 7.09-7.12 (m, 2H, Ar-H), 7.17-7.24 (m, 3H, Ar-H), 7.42-7.43 (m, 6H,Ar-H), 7.48-7.56 (m, 6H, Ar-H), 7.58-7.59 (m, 3H, Ar-H); 13C-NMR (CDCl3) delta (ppm) 50.9, 56.3 (d, 1JCP = 118.2 Hz), 111.6, 114.4, 123.4 (d, 1JCP = 92.4 Hz), 128.5, 128.6, 129.1, 129.2, 133.0, 133.4,133.5, 133.6, 150.9, 151.6, 153.4 (d, 2JCP = 12.3 Hz), 171.2 (d, 2JCP = 6.6 Hz); HRMS (ESI) calcd for C32H25N5O4P 574.1638 [M + H]+, found 574.1631.
  • 42
  • [ 645-12-5 ]
  • [ 83558-37-6 ]
  • N-(4-(3-methoxyphenyl)thiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
63.7% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure: (iv) 10a-10n (2 mmol, 1.0 equiv.) wasdissolved in dry dichloromethane (10 mL), and the reaction was followed to add 5-nitro-2-furoicacid (2.4 mmol, 1.2 equiv.), DMAP (2.4 mmol, 1.2 equiv.), EDCI (4 mmol, 2.0 equiv.),then stirred under room temperature for 1 day. The reaction mixture wasquenched with H2O (10 mL) and extracted with dichloromethane (2*30 mL).The combined organic layers were washed in turn with 2N HCl (20 mL), H2O(20 mL) and brine (20 mL). The organic layer was collected, dried overanhydrous Na2SO4 and concentrated in vacuo. The residue waspurified by column chromatography on silica gel (hexane/EtOAc=8:1 to 4:1) toprovide 12a-12n. 11a and 11b were prepared by thesame way, just starting from 10b and replacing 5-nitro- furic with2-furoic acid and 4-nitrobenzoic acid. The yield was 29~80%.
  • 43
  • [ 645-12-5 ]
  • [ 2104-04-3 ]
  • N-(4-(4-methoxyphenyl)thiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure: (iv) 10a-10n (2 mmol, 1.0 equiv.) wasdissolved in dry dichloromethane (10 mL), and the reaction was followed to add 5-nitro-2-furoicacid (2.4 mmol, 1.2 equiv.), DMAP (2.4 mmol, 1.2 equiv.), EDCI (4 mmol, 2.0 equiv.),then stirred under room temperature for 1 day. The reaction mixture wasquenched with H2O (10 mL) and extracted with dichloromethane (2*30 mL).The combined organic layers were washed in turn with 2N HCl (20 mL), H2O(20 mL) and brine (20 mL). The organic layer was collected, dried overanhydrous Na2SO4 and concentrated in vacuo. The residue waspurified by column chromatography on silica gel (hexane/EtOAc=8:1 to 4:1) toprovide 12a-12n. 11a and 11b were prepared by thesame way, just starting from 10b and replacing 5-nitro- furic with2-furoic acid and 4-nitrobenzoic acid. The yield was 29~80%.
  • 44
  • [ 90533-23-6 ]
  • [ 645-12-5 ]
  • N-(4-(3-chlorophenyl)thiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
47.7% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 24h; General procedure: (iv) 10a-10n (2 mmol, 1.0 equiv.) wasdissolved in dry dichloromethane (10 mL), and the reaction was followed to add 5-nitro-2-furoicacid (2.4 mmol, 1.2 equiv.), DMAP (2.4 mmol, 1.2 equiv.), EDCI (4 mmol, 2.0 equiv.),then stirred under room temperature for 1 day. The reaction mixture wasquenched with H2O (10 mL) and extracted with dichloromethane (2*30 mL).The combined organic layers were washed in turn with 2N HCl (20 mL), H2O(20 mL) and brine (20 mL). The organic layer was collected, dried overanhydrous Na2SO4 and concentrated in vacuo. The residue waspurified by column chromatography on silica gel (hexane/EtOAc=8:1 to 4:1) toprovide 12a-12n. 11a and 11b were prepared by thesame way, just starting from 10b and replacing 5-nitro- furic with2-furoic acid and 4-nitrobenzoic acid. The yield was 29~80%.
  • 45
  • [ 105512-81-0 ]
  • [ 645-12-5 ]
  • N-(4-(3-bromophenyl)thiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure: (iv) 10a-10n (2 mmol, 1.0 equiv.) wasdissolved in dry dichloromethane (10 mL), and the reaction was followed to add 5-nitro-2-furoicacid (2.4 mmol, 1.2 equiv.), DMAP (2.4 mmol, 1.2 equiv.), EDCI (4 mmol, 2.0 equiv.),then stirred under room temperature for 1 day. The reaction mixture wasquenched with H2O (10 mL) and extracted with dichloromethane (2*30 mL).The combined organic layers were washed in turn with 2N HCl (20 mL), H2O(20 mL) and brine (20 mL). The organic layer was collected, dried overanhydrous Na2SO4 and concentrated in vacuo. The residue waspurified by column chromatography on silica gel (hexane/EtOAc=8:1 to 4:1) toprovide 12a-12n. 11a and 11b were prepared by thesame way, just starting from 10b and replacing 5-nitro- furic with2-furoic acid and 4-nitrobenzoic acid. The yield was 29~80%.
  • 46
  • [ 645-12-5 ]
  • [ 172848-41-8 ]
  • 5-nitro-N-(4-(3-(trifluoromethyl)phenyl)thiazol-2-yl)furan-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35.2% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; General procedure: (iv) 10a-10n (2 mmol, 1.0 equiv.) wasdissolved in dry dichloromethane (10 mL), and the reaction was followed to add 5-nitro-2-furoicacid (2.4 mmol, 1.2 equiv.), DMAP (2.4 mmol, 1.2 equiv.), EDCI (4 mmol, 2.0 equiv.),then stirred under room temperature for 1 day. The reaction mixture wasquenched with H2O (10 mL) and extracted with dichloromethane (2*30 mL).The combined organic layers were washed in turn with 2N HCl (20 mL), H2O(20 mL) and brine (20 mL). The organic layer was collected, dried overanhydrous Na2SO4 and concentrated in vacuo. The residue waspurified by column chromatography on silica gel (hexane/EtOAc=8:1 to 4:1) toprovide 12a-12n. 11a and 11b were prepared by thesame way, just starting from 10b and replacing 5-nitro- furic with2-furoic acid and 4-nitrobenzoic acid. The yield was 29~80%.
  • 47
  • [ 645-12-5 ]
  • 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine [ No CAS ]
  • (4-(4-morpholino-6-((3,4,5-trimethoxyphenyl)amino)-1,3,5-triazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)(5-nitrofuran-2-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 8h; General procedure: To a stirred solution of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine (5) (0.3g, 0.7mmol) in DCM, acid (0.7mmol), triethylamine (0.21g, 2.1mmol), HOBt (21mg, 0.14mmol), EDC.HCl (0.26g, 1.4mmol) were added at RT and allowed stirred for 8h. Reaction was monitored by TLC and water was added to reaction mixture once complete and was followed by extraction with ethyl acetate. Combined organic layers were collected and dried over dry sodium sulfate. Concentrated the organic layers and purified by column chromatography with 45% ethyl acetate in petroleum ether.
  • 48
  • [ 645-12-5 ]
  • (2S,4S)-4-hydroxy-4-((3aR,7S,8aS)-7-methyl-3-methylene-2-oxo-3,3a,4,7,8,8a-hexahydro-2H-cyclohepta[b]furan-6-yl)butan-2-yl acetate [ No CAS ]
  • (1S,3S)-3-acetoxy-1-((3aR,7S,8aS)-7-methyl-3-methylene-2-oxo-3,3a,4,7,8,8a-hexahydro-2H-cyclohepta[b]furan-6-yl)butyl 5-nitrofuran-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% General procedure: In a two-necked round bottom flask equipped with a calciumchloride drying tube was charged aryl carboxylic acid(1 equiv.), isoxanthanol (1) (1 equiv.), and DMAP (10 mol%) in dry dichloromethane. The resulting reaction mixturecooled in an ice bath to 0 C and stirred for a while followedby addition of DCC (1.1 equiv.) at 0 C over a period of 5min. The ice bath was removed, and the dark-brown reactionmixture stirred for 3 h at room temperature. Aftercompletion of the reaction, the precipitate of dicyclohexylureawas removed by filtration through a fritted Buchnerfunnel, and the filtrate washed with water and extracted withdichloromethane. The organic layer was dried over anhydroussodium sulfate and concentrated on a rotavapor. The crude product obtained was purified by CC on silica gelcolumn using hexane-ethyl acetate as the eluent.
  • 49
  • [ 268209-15-0 ]
  • [ 645-12-5 ]
  • (S)-tert-butyl-4-(2-fluoro-4-(5-((5-nitrofuran-2-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)piperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 8h;Inert atmosphere; Cooling with ice; To a stirred solution of 8a (394 mg, 1 mmol) in CH2Cl2 (15 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride (EDC) (382 mg, 2 mmol) in ice bath followed by the addition of 5-nitro furoic acid (314 mg, 2 mmol). The resulting mixture was stirred at room temperature until completion of the reaction as indicated by TLC. The reaction mixture was neutralized by sodium bicarbonate solution and extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue, thus, obtained was purified by column chromatography on silica gel using ethyl acetate/hexane (7:3) to afford pure compound (9a). Yield: 88%; 1HNMR (300 MHz, CDCl3): delta 7.99 (1H, t, J = 6.04 Hz), 7.39 (1H, dd, J = 12.27, 2.45 Hz), 7.33 (1H, d, J = 3.77 Hz), 7.26 (1H, d, J = 3.77 Hz), 7.06 (1H, dd, J = 6.98, 1.88 Hz), 6.89 (1H, t, J = 9.25, 8.87 Hz), 4.92 (1H, m), 4.14 (1H, t, J = 9.06, 8.87 Hz), 4.00-3.92 (1H, m), 3.84-3.74 (2H,m), 3.58 (4H, m), 2.97 (4H, m), 1.48 (9H, s); ESI-MS: m/z = 534 (M + 1)+.
  • 50
  • [ 645-12-5 ]
  • [ 383131-87-1 ]
  • N-[5-(tetrahydrofuran-2-yl)-[1,3,4]thiadiazol-2-yl]-(5-nitrofuran-2-yl)carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
55.5% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In dichloromethane at 20℃; for 3h; 3.c c) The solid obtained in the previous step was dissolved in 50 mL of dichloromethane, and 5-nitrofuran-2-carboxylic acid (12.56 g, 0.08 mol) was added.2-(7-Oxobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (45.6 g, 0.12 mol) was stirred at room temperature for 3 hr.After adding 100 mL of water, the mixture was extracted with EtOAc.The organic solvent was distilled off under reduced pressure, and the residue was applied to silica gel column ( petroleum ether: ethyl acetate = 5:1 to 3:1).Concentrated to a pale yellow solid, 17.2 g, a three-step total yield of 55.5%.
  • 51
  • [ 645-12-5 ]
  • 3-amino-6-trifluoromethylquinoxaline-2-carbonitrile-N1,N4-dioxide [ No CAS ]
  • [ 1207614-08-1 ]
YieldReaction ConditionsOperation in experiment
51.8% General procedure: To a solution of the corresponding 3-amino-1,4-di-N-oxide-quinoxaline-2-carbonitrile II (2 mmol)in DMF (5 mL) are added 5-nitrothiophene-2-carboxylic acid or 5-nitrofuran-2-carboxylic acid (3mmol). The reaction mixture is then gently stirred at room temperature under anhydrous conditions. Continuing with the synthesis, N-(3-dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride(EDCI, 6 mmol) are added, and the color changes to dark-red. When the dissolution is completed, 4-dimethyl-aminopyridine (DMAP, 6 or 7 mmol) are added. The reaction mixture is stirred between 17h-72 h. After that, EtOAc (200 mL) is added and the organic phase is extracted, first with 10% HCland then with saturated NaHCO3. The basic phase is treated with HCl 37% until pH 2, usually shownby the color changing to yellow. This phase is extracted with dichloromethane (3 × 75 mL), dried withanhydrous Na2SO4 and filtered. The solvent is removed in vacuo. The resulting residue is precipitatedwith diethyl ether and filtered in order to obtain a yellow-orange solid. Sometimes, when DMAP isadded, the compound precipitates due to its acidity. In those cases, HCl (300 mL) is added and themixture is stirred gently. The 3-amino-1,4-di-N-oxide-quinoxaline-2-carbonitrile derivatives aredissolved, and the precipitated compound is filtered. The compound is first washed with 10% HCl andthen with diethyl ether.
  • 52
  • [ 645-12-5 ]
  • C13H12N2O5S*ClH [ No CAS ]
  • 2-methoxy-4-((5-nitrofuran-2-carboxamido)methyl)phenyl 5-nitrothiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 24h; General procedure: Compound 10 (370 mg, 0.9 mmol), carboxylic acid (0.9 mmol),triethylamine (0.25 mL, 1.8 mmol) and HATU (340 mg, 0.9 mmol)were added into DMF at room temperature. After stirred for 24 h,the mixture is extracted with EA and saturated brine. The organicphase was washed with 1N HCl and 1N NaOH, then dried andevaporated. The residue was purified by column (eluent: PE/EA, v/v 3:1-1:1) to yield the product.
  • 53
  • [ 1849-71-4 ]
  • [ 645-12-5 ]
  • N-(4,5-dichloro-1,3-benzothiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
3 mg Stage #1: 5-nitro-2-furoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.5h; Stage #2: 4,5-dichloro-1,3-benzothiazol-2-amine With triethylamine In dichloromethane at 20℃;
  • 54
  • [ 645-12-5 ]
  • [ 65373-18-4 ]
  • N‐(5‐chloro‐4‐methyl‐1,3‐benzothiazol‐2‐yl)‐5‐nitrofuran‐2‐carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
9 mg Stage #1: 5-nitro-2-furoic acid With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In N,N-dimethyl-formamide for 0.5h; Stage #2: 5-chloro-4‐methyl‐1,3‐benzothiazol-2-amine With triethylamine In N,N-dimethyl-formamide
  • 55
  • [ 645-12-5 ]
  • [ 7659-07-6 ]
  • N-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% General procedure: To a stirring solution of 4 (158.0mg, 1.0mmol) in DCM (5.0mL) were added HATU (456.0mg, 1.2mmol) and TEA (278.0µl, 2.0mmol). After stirring for 0.5h at room temperature, commercially available 7a-m (1.0mmol) was added and stirred for 1.5-2.5h. The reaction mixture was washed with brine and saturated NaHCO3 aq. The organic phase was concentrated and purified over silica gel column (DCM:MeOH=30:1) to yield 2a-m in a yield of 22-31%.
  • 56
  • [ 645-12-5 ]
  • [ 33621-62-4 ]
  • N-(5-(4-bromophenyl)-1,3,4-oxadiazol-2-yl)-5-nitrofuran-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% Stage #1: 5-nitro-2-furoic acid With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 0.5h; Stage #2: 2-amino-5-(4'-bromophenyl)-1,3,4-oxadiazole In dichloromethane at 20℃; 4.2.2 General procedure for the preparation of 2a-m General procedure: To a stirring solution of 4 (158.0mg, 1.0mmol) in DCM (5.0mL) were added HATU (456.0mg, 1.2mmol) and TEA (278.0µl, 2.0mmol). After stirring for 0.5h at room temperature, commercially available 7a-m (1.0mmol) was added and stirred for 1.5-2.5h. The reaction mixture was washed with brine and saturated NaHCO3 aq. The organic phase was concentrated and purified over silica gel column (DCM:MeOH=30:1) to yield 2a-m in a yield of 22-31%.
  • 57
  • [ 645-12-5 ]
  • [ 5711-72-8 ]
  • 5-nitro-N-(5-(pyridin-2-yl)-1,3,4-oxadiazol-2-yl)furan-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
23% General procedure: To a stirring solution of 4 (158.0mg, 1.0mmol) in DCM (5.0mL) were added HATU (456.0mg, 1.2mmol) and TEA (278.0µl, 2.0mmol). After stirring for 0.5h at room temperature, commercially available 7a-m (1.0mmol) was added and stirred for 1.5-2.5h. The reaction mixture was washed with brine and saturated NaHCO3 aq. The organic phase was concentrated and purified over silica gel column (DCM:MeOH=30:1) to yield 2a-m in a yield of 22-31%.
  • 58
  • [ 5711-73-9 ]
  • [ 645-12-5 ]
  • 5-nitro-N-(5-(pyridin-3-yl)-1,3,4-oxadiazol-2-yl)furan-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% Stage #1: 5-nitro-2-furoic acid With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 0.5h; Stage #2: 2-amino-5-(3-pyridinyl)-1,3,4-oxadiazole In dichloromethane at 20℃; 4.2.2 General procedure for the preparation of 2a-m General procedure: To a stirring solution of 4 (158.0mg, 1.0mmol) in DCM (5.0mL) were added HATU (456.0mg, 1.2mmol) and TEA (278.0µl, 2.0mmol). After stirring for 0.5h at room temperature, commercially available 7a-m (1.0mmol) was added and stirred for 1.5-2.5h. The reaction mixture was washed with brine and saturated NaHCO3 aq. The organic phase was concentrated and purified over silica gel column (DCM:MeOH=30:1) to yield 2a-m in a yield of 22-31%.
  • 59
  • [ 645-12-5 ]
  • [ 46182-58-5 ]
  • 5-nitro-N-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)furan-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
117.0 mg Stage #1: 5-nitro-2-furoic acid With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 0.5h; Stage #2: (5-phenyl-1,3,4-oxadiazol-2-yl)methanamine In dichloromethane at 20℃; General procedure: To a stirring solution of 4 (158.0mg, 1.0mmol) in DCM (5.0mL) were added HATU (456.0mg, 1.2mmol) and TEA (278.0µl, 2.0mmol). After stirring for 0.5h at room temperature, commercially available 7a-m (1.0mmol) was added and stirred for 1.5-2.5h. The reaction mixture was washed with brine and saturated NaHCO3 aq. The organic phase was concentrated and purified over silica gel column (DCM:MeOH=30:1) to yield 2a-m in a yield of 22-31%.
  • 60
  • [ 645-12-5 ]
  • [ 517-88-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; General procedure for C1′ -OH esterification of alkannin General procedure: A solution of alkannin (1 equiv.) in anhydrous DCM (20 ml) was cooled to 0 C. After that, the amino acids containing Boc protective groups or oxygen-containing heterocycles acids (1.2 equiv.), DCC (1.2 equiv.) and DMAP (0.1 equiv.) were added. In the process of reaction, the product was monitored by TLC. After stirring at 0 C for 4 h, petroleum ether was added to the reaction solution to promote the sedimentation and placed in - 20 C overnight. The by-product DCU was then filtered twice, and the filtrate was evaporated under vacuum. Purification of the residual oil was carried out by flash chromatography (silica gel, petroleum: Ethyl acetate: Formic acid = 50: 1: 1) to give as red oil.
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; General procedure for C1′ -OH esterification of alkannin General procedure: A solution of alkannin (1 equiv.) in anhydrous DCM (20 ml) was cooled to 0 C. After that, the amino acids containing Boc protective groups or oxygen-containing heterocycles acids (1.2 equiv.), DCC (1.2 equiv.) and DMAP (0.1 equiv.) were added. In the process of reaction, the product was monitored by TLC. After stirring at 0 C for 4 h, petroleum ether was added to the reaction solution to promote the sedimentation and placed in - 20 C overnight. The by-product DCU was then filtered twice, and the filtrate was evaporated under vacuum. Purification of the residual oil was carried out by flash chromatography (silica gel, petroleum: Ethyl acetate: Formic acid = 50: 1: 1) to give as red oil.
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