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[ CAS No. 39070-14-9 ] {[proInfo.proName]}

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Chemical Structure| 39070-14-9
Chemical Structure| 39070-14-9
Structure of 39070-14-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 39070-14-9 ]

CAS No. :39070-14-9 MDL No. :MFCD06738747
Formula : C5H7N3O3 Boiling Point : -
Linear Structure Formula :- InChI Key :WXSSUDRHAJTESR-UHFFFAOYSA-N
M.W : 157.13 Pubchem ID :70292
Synonyms :

Calculated chemistry of [ 39070-14-9 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.4
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 38.44
TPSA : 83.87 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) : -7.51 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.43
Log Po/w (XLOGP3) : -0.35
Log Po/w (WLOGP) : -0.33
Log Po/w (MLOGP) : -1.16
Log Po/w (SILICOS-IT) : -1.89
Consensus Log Po/w : -0.66

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.8
Solubility : 25.0 mg/ml ; 0.159 mol/l
Class : Very soluble
Log S (Ali) : -0.95
Solubility : 17.7 mg/ml ; 0.112 mol/l
Class : Very soluble
Log S (SILICOS-IT) : 0.01
Solubility : 159.0 mg/ml ; 1.01 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.19

Safety of [ 39070-14-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 39070-14-9 ]

* 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 [ 39070-14-9 ]

[ 39070-14-9 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 39070-14-9 ]
  • C13H22Cl4N5O4P [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a suspension of bis(2-chloroethyl)ammonium chloride (1.43 g, 8.01 mmol) in dichloromethane (DCM) phosphorus trichloride (0.32 ml, 3.64 mmol) was added at rt followed by addition of TEA (3.05 ml, 21.84 mmol). The reaction mixture was stirred at rt for 30 minutes and then N-methyl 2-nitroimidazolyl methanol (0.474 g, 3.31 mmol) in DME was added. After stirring for 0.5 hour, the reaction mixture was cooled to -2O0C and tert- butyl hydroperoxide (0.7 ml, 3.82 mmol, 5.5 M in Decane) was added. The reaction mixture was warmed to rt over a period of one hour, and poured into 10% aqueous HCl. The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic solution was dried with MgSO4 and concentrated to yield a residue which was purified by flash chromatography with 6-12% methanol in DCM yielding 6.
  • 2
  • [ 31645-39-3 ]
  • [ 39070-14-9 ]
  • (2-chloroethyl)([(2-chloroethyl)amino][(2-nitro-3-methylimidazol-4-yl)methoxy]phosphoryl})amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 2h; To a solution of N-methyl-2-mtxoimidazole-5-methanol (180 mg, 1.14 mmol), triphenylphosphine (300 mg, 1.14 mmol), and isophosphoramide mustard (Ic, 127 mg, 0.57 mmol) in THF (10 ml) diisopropyl azodicarboxylate (DIAD, 0.22ml, 1.14 mmol) was added dropwise at rt. After two hours reaction mixture was concentrated and the residue separated by flash chromatography with 30-100% acetone in toluene yielding compound_36.
  • 3
  • [ 918633-72-4 ]
  • [ 39070-14-9 ]
  • C9H8(2)H8Br2N5O4P [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 2h; 48% HBr (60 mL) was added dropwise to J4-ethanolamine at O0C. The reaction mixture was stirred for lhr at rt and then gently refluxed and slowly distilled, 16 mL liquid being collected in 2 hrs until 1550C (oil bath). This was replaced twice with 60 mL of 48% HBr and the distillation continued for an additional 5 hr. 90 mL liquid was collected. The resultant solution was heated at 1650C for 2hr and evaporated under vacuum. The residue was recrystalled from an absolute ethol (10 mL)-ethyl acetate (30 mL) to 11.3g of <i4-2- bromoethamine hydrobromide (compound 64i). Compound 64i (19.5 mmol, 1.0 eq.) was added dropwise to a suspension of <3?4-2-bromoethamine hydrobromide (40.0 mmol, 2.05 eq.) in dry DCM (100 mL) under argon,at -2O0C, followed by the dropwise addition of TEA (81.9 mmol, 4.2 eq.) at -2O0C. The reaction mixture was stirred at -200C for 0.5 h, and at rt for 2 h, poured into water, and extracted twice with DCM (30 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure to yield a residue which was separated by column chromatography on silica gel employing as eluent Hexane/EA (100:70(v/v)) to yield 7.0 g of compound 64ii. PtO2 (0.7 g) was added to a solution of compound 64ii (7.0 g) in MeOH (160 mL), the reaction mixture degassed and exchanged with H2 thrice, stirred under H2 for 3 h at rt, and diluted with MeOH until the EPO <DP n="139"/>white solid in the reaction mixture dissolved. The diluteed reaction mixture was filtered, the filtrate concentrated under reduced pressure to yield a residue ehich was washed with anhydrous ether twice to yield 2.9 g of compound 64iii. To a suspension of compounds 64iii (1.92 g 1.0 eq.), l-N-methyl-2-nitroimidazolemethanol (1.01 g, 1.1 eq.), and PPh3 (2.39 g, 1.5 eq.) in THF (20 mL) was added DIAD (1.76 ml, 1.5 eq.), under argon, at O0C. The reaction mixture was stirred for 2 hours while being warmed up from O0C to rt, following which volatiles were removed under vacuum to yield a residue. The residue was separated by flash chromatography on silica gel employing as eluent Acetone/Toluene (100:70(v/v)) to yield 1.35 g of compound 64.
  • 4
  • [ 39070-14-9 ]
  • (1-methyl-2-nitro-1H-imidazol-5-yl)methyl 1-(chloromethyl)-3-[(5,6,7-trimethoxy-1H-indol-1-yl)carbonyl]-2,3-dihydro-1H-benzo[e]indol-5-ylcarbamate [ No CAS ]
  • 5
  • [ 39070-14-9 ]
  • {4-[bis-(2-chloro-ethyl)-amino]-phenyl}-carbamic acid 3-methyl-2-nitro-3<i>H</i>-imidazol-4-ylmethyl ester [ No CAS ]
  • 6
  • [ 39070-14-9 ]
  • [ 304015-64-3 ]
  • 7
  • [ 39070-14-9 ]
  • methanesulfonic acid 2-{(2-methanesulfonyloxy-ethyl)-[4-(3-methyl-2-nitro-3<i>H</i>-imidazol-4-ylmethoxycarbonylamino)-phenyl]-amino}-ethyl ester [ No CAS ]
  • 8
  • [ 39070-14-9 ]
  • [ 304015-63-2 ]
  • 9
  • [ 39070-14-9 ]
  • (1-methyl-2-nitro-1H-imidazol-5-yl)methyl bis(2-chloroethyl)carbamate [ No CAS ]
  • 10
  • 2-amino-5-carbethoxy-1-methylimidazole hydrochloride [ No CAS ]
  • [ 39070-14-9 ]
  • 11
  • [ 39070-14-9 ]
  • 2-(2-amino-3-methyl-3<i>H</i>-imidazol-4-ylmethyl)-5-bromo-2<i>H</i>-isoquinolin-1-one [ No CAS ]
  • 13
  • [ 39070-14-9 ]
  • 5-bromo-2-(2-hydroxyamino-3-methyl-3<i>H</i>-imidazol-4-ylmethyl)-2<i>H</i>-isoquinolin-1-one [ No CAS ]
  • 14
  • [ 75-44-5 ]
  • [ 250698-52-3 ]
  • [ 39070-14-9 ]
  • N4-(2-nitro-1-methylimidazol-5-yl)methoxycarbonyl-3',5'-di-O-t-butoxycarbonyl-2',2'-difluoro-2'-deoxycytidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% With pyridine; In dichloromethane; toluene; at 0℃; for 48h; N4-(2-nitro-l-methylimidazol-5-yl)methoxycarbonyl-3',5'-di-O-t-butoxycarbonyl-2',2'-difluoro-2'-deoxycytidine (80 mg, 0.124 mmol) was dissolved in DCM (4 niL) then cooled to 0C. TFA (1.5 niL) was added drop wise to the cooled reaction mixture and stirring continued for 4 h. Silica gel (1.0 g) was then added together with DCM (5 mL) and then the reaction mixture was evaporated. Flash chromatography, eluting with 100% ethyl acetate then 10% methanol / ethyl acetate, furnished an oil. The oil was triturated with ether to give a white solid (50 mg, 100%). NMR (500Mhz, DMSO-d6, delta)11.09 (IH, s, NH), 8.36 (IH, s, NCH), 7.07 (IH, m, HarH), 6.34 (IH, s, NCHCF2), 6.18 (IH, m, OH), 5.32 (3H, m, OCH2 & OH), 4.20 (IH, bs, CHOH), 3.95 (3H, s, NCH3)3.89 (IH, m, OCHCH2OH), 3.80 (IH, m, CH2OH), 3.65 (IH, m, CH2OH) ppmN4-(2-nitro-l-methylimidazol-5-yl)methoxycarbonyl-3',5'-di-O-t-butoxycarbonyl- 2',2'-difluoro-2'-deoxycytidine was synthesized as follows: 5-Hydroxymethyl-l- methyl-2-nitroimidazole (157 mg, 1.00 mmol), 3',5'-di- O-t-butoxycarbonyl -2',2'- difluoro-2'-deoxycytidine (200 mg, 0.43 mmol), pyridine (0.20 mL, 2.54 mmol) and DCM (3 mL) were stirred at O0C. A solution of phosgene (0.25 mL, 0.50 mmol, 2 M in toluene) was added dropwise to the reaction mixture and stirring continued for 48 EPO <DP n="35"/>h. The reaction mixture was partitioned (ethyl acetate and water), the aqueous phase was extracted (ethyl acetate), the organic phases were combined, washed (water then brine) then dried (Na2SO4) and evaporated. Flash chromatography, eluting with 33% ethyl acetate / hexane then 100% ethyl acetate, furnished a yellow oil (80 mg, 29%).
  • 15
  • [ 98-59-9 ]
  • [ 39070-14-9 ]
  • [ 4111-54-0 ]
  • [ 87544-76-1 ]
YieldReaction ConditionsOperation in experiment
12 g (50%) With n-butyllithium; diisopropylamine; In tetrahydrofuran; N-methyl-acetamide; hexane; dichloromethane; EXAMPLE 7 A lithium diisopropylamine solution (prepared from 65 ml of a 2.2 molar solution of butyl lithium in hexane and 14.5 g of diisopropylamine in 150 ml of tetrahydrofuran) was added dropwise at a temperature of -60 C. within 15 minutes to a solution of 22 g of 1-methyl-2-nitroimidazole-5-methanol in 300 ml of tetrahydrofuran and 150 ml of dimethylformamide. The mixture was stirred at -60 C. for 30 minutes and treated with 28 g of p-toluenesulphonyl chloride in 150 ml of tetrahydrofuran. After removing the cooling, warming to room temperature and adding 300 ml of ice/water, the mixture was extracted three times with 300 ml of ethyl acetate each time. The combined extracts were washed with 150 ml of saturated sodium chloride solution and evaporated under reduced pressure. The residue was purified on 800 g of silica gel with ethyl acetate/dichloromethane (1:3, v/v). After a forerun of 1.5 l, the next 1.5 l were collected and evaporated. Recrystallization from 70 ml of toluene yielded 12 g (50%) of 5-(chloromethyl)-1-methyl-2-nitroimidazole, m.p. 100-101 C.
  • 16
  • [ 123-30-8 ]
  • [ 39070-14-9 ]
  • α-(1-methyl-2-nitroimidazol-5-yl)-p-anisidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
24.4 g (52%) With diisopropyl (E)-azodicarboxylate; triphenylphosphine; In tetrahydrofuran; dichloromethane; ethyl acetate; EXAMPLE 6 A suspension of 30 g of 1-methyl-2-nitroimidazole-5-methanol, 22 g of 4-aminophenol and 55 g of triphenylphosphane in 600 ml of anhydrous tetrahydrofuran was treated dropwise with vigorous stirring within 20 minutes with a solution of 42.5 g of diisopropyl azodicarboxylate in 300 ml of anhydrous tetrahydrofuran. The mixture was maintained at a temperature of 20-24 C. by external cooling. After 2 hours, the clear solution obtained was evaporated under reduced pressure and the residue was boiled briefly with a mixture of 125 ml of methylene chloride and 125 ml of ethyl acetate to yield 24.4 g (52%) of crystalline alpha-(1-methyl-2-nitroimidazol-5-yl)-p-anisidine, m.p. 168-170 C.
  • 17
  • [ 2153-11-9 ]
  • [ 39070-14-9 ]
  • 2-chloro-α-(1-methyl-2-nitroimidazol-5-yl)-p-acetanisidide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90.9 g (56.6%) With diisopropyl (E)-azodicarboxylate; triphenylphosphine; In tetrahydrofuran; EXAMPLE 1 78.5 g of 1-methyl-2-nitroimidazole-5-methanol were suspended in 1.5 l of anhydrous tetrahydrofuran. After the addition of 102 g of p-chloroacetylaminophenol and 144 g of triphenylphosphane, the mixture was cooled to 10 C. and a solution of 111 g of diisopropyl azodicarboxylate in 750 ml of anhydrous tetrahydrofuran was added thereto with vigorous stirring within 20 minutes, the temperature being held at 10-12 C. by means of an ice-bath. The mixture was stored in a refrigerator overnight and the crystalline precipitate was filtered off under suction. Recrystallization from 2 l of acetonitrile, yielded 90.9 g (56.6%) of pure 2-chloro-alpha-(1-methyl-2-nitroimidazol-5-yl)-p-acetanisidide, m.p. 192-194 C. (decomposition).
  • 18
  • [ 39928-74-0 ]
  • [ 39070-14-9 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium tetrahydroborate; In ethanol; EXAMPLE 57: 1-Methyl-2-nitro-5-hydroxymethylimidazole To a solution of 1.55 g. of 1-methyl-2-nitro-5-imidazolecarboxaldehyde in 200 ml. of ethanol, a solution of 1.9 g. of NaBH4 in 150 ml. of ethanol is added at about -4 C. After stirring for 15 minutes at 0 C., the excess of NaBH4 is decomposed with 10% hydrochloric acid and the reaction mixture is filtered. the residue, which is obtained by evaporation of the filtrate, is crystallized from acetone and yield 1 g. of the title product which melts at 142-144 C.
  • 19
  • [ 39070-14-9 ]
  • [ 39928-74-0 ]
YieldReaction ConditionsOperation in experiment
98% With Dess-Martin periodane; In dichloromethane; at 20℃; for 1h;Inert atmosphere; Normethyl nitroimidazole trigger 28 (359 mg, 2.28 mmol) was dissolved in CH2Cl2 (10 mL). Dess-Martin periodinane (1.16 g, 2.74 mmol) was added and the reaction mixture was stirred for 1 h at room temperature. Saturated solutions of NaHCO3 (20 mL) and sodium thiosulfate (20 mL) were added to the reaction mixture, which was extracted with EtOAc (3 x 25 mL). The combined organic layers were dried over Na2SO4 and filtered, and the solvent was removed under reduced pressure. Purification by flash chromatography using a prepacked 25 g silica column [solvent A: EtOAc; solvent B: hexanes; gradient: 12%A / 88%B (1 CV), 12%A / 88%B ? 100%A / 0%B (10 CV), 100%A / 0%B (2 CV); flow rate: 75 mL/min; monitored at 254 and 280 nm] afforded imidazole analogue (346 mg, 2.23 mmol, 98%) as a yellow solid.1H NMR (600 MHz, CDCl3) delta 9.94 (1H, s), 7.82 (1H, s), 4.36 (3H, s).13C NMR (151 MHz, CDCl3) delta 180.39, 148.35, 139.38, 132.38, 35.57.
76% With manganese(IV) oxide; In chloroform; for 18h;Reflux; To alcohol18(1.0 g, 6.36 mmol) in chloroform (70 mL) was added MnO2(2.76 g, 31.8 mmol) and the mixture was heated to reflux overnight. After cooling, the resulting slurry was filtered through diatomaceous earth and solvent removed in vacuo to yield19(1.5 g, 76%) as a pale yellow solid, mp 112-114 C (lit. [62] mp 114-115 C). deltaH(CDCl3) 9.93 (1H, s, CHO), 7.81 (1H, s, H-4), 4.36 (3H, s, CH3). deltaC(CDCl3) 180.4 (C = O), 148.3 (C-NO2), 139.4 (CH), 132.4 (CH), 35.6 (CH3). LRMS 188.1 (100%, M + CH3OH). These data are in good agreement with literature values [35].
With manganese dioxide; In benzene; EXAMPLE 61: 1-Methyl-2-nitro-5-imidazolaldehyde To a solution of 0.15 g. of <strong>[39070-14-9]1-methyl-2-nitro-5-hydroxymethylimidazole</strong> in 20 ml. of benzene, 0.33 g. of MnO2 is added and the reaction mixture is heated on the steambath for 2 hours. After filtration and evaporation to dryness under vacuum, the crude product is crystallized from ethyl acetate and 0.060 g. (40.5%) of 1-methyl-2-nitro-5-imidazolaldehyde is obtained.
  • 20
  • [ 1014975-27-9 ]
  • [ 39070-14-9 ]
  • C11H20Cl2N5O4P [ No CAS ]
  • 21
  • [ 141025-16-3 ]
  • [ 39070-14-9 ]
  • N,N’-bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 25℃; for 2h; [0103j Imidazole alcohol (IA) (1:1.0 w/w), Bromo-IPM (1:2.26 w/w) and triphenylphosphine (1:2.0 w/w) were added to THF (1:13.5 w/v) at 25±5C. The reaction mass was cooled to 0±5C and DIAD (1.5 w/v) was added. The reaction mixture warmed to 25±5C and stirred for 2 hours. Progress of the reaction was monitored by HPLC. Solvent was removed below 50C under vacuum. Solvent exchange with acetonitrile (1:10.0 w/v) below 50C was performed. The syrupy liquid was re-dissolved in acetonitrile (1:10.0 w/v)and the mixture was stirred at -20±5C for 1 hour. The resulting solid was filtered and the filtrate bed was washed with chilled acetonitrile (1:1.0 w/v). The acetonitrile filtrate was concentrated below 50C under vacuum. The concentrated mass was re-dissolved in ethyl acetate (1:10.0 w/v) and concentrated below 50C under vacuum. The ethyl acetate strip off was repeated two more times. Ethyl acetate (1:10.0 w/v) and silica gel (230-400 mesh, 1:5.3w/w) were added to the concentrated reaction mass. The mixture was concentrated below40C under vacuum. n-Heptane (1:5.0 w/v) was charged to the above mass and the mixture was evaporated below 40C under vacuum. n-Heptane (1:5.0 w/v) was again added to the above mass and the solid was filtered and the bed was washed with n-heptane (1:1.0 w/v). The solid was suspended in a mixture of toluene (1:7.1 w/v) and n-heptane (1:21.3 w/v),stirred at 35±5C for 15-20 minutes, filtered off and the bed was washed with n-heptane (1:1.0 w/v). The solid was re-suspended in a mixture of toluene (1:10.6 w/v) and n-heptane (1:10.6 w/v), stirred at 35±5C for 15-20 minutes, filtered off and the bed was washed with nheptane (1:1.0 w/v). The solid was suspended in acetone (1:19.0 w/v), stirred at 35±5C for 15-20 minutes, filtered off and the bed was washed with acetone (1:1.0 w/v). The acetonewashes were repeated 3 more times. Filtrates from the above acetone washings were combined and concentrated below 40C under vacuum. The residue dissolved in ethyl acetate (1:10.0 w/v) and concentrated below 40C under vacuum. The ethyl acetate strip off was repeated one more time. The residue was re-dissolved in ethyl acetate (1:5.5 w/v), cooled to 0±3C and stirred at 0±3C for 2 h and then at -20±5C for 2 h. The solid wasfiltered and the solid was washed with ethyl acetate (1:0.10 w/v). The solid was dissolved in ethyl acetate (1:10.0 w/v) at 50±5C and the resulting solution was filtered through a cartridge filter. The filtrate was concentrated to 4.0 w/w and stirred at 0±3C for 4 hours. The solid was filtered and washed with ethyl acetate (1:0.10 w/v). The crystallization from ethyl acetate was repeated and TH-302 was dried at 25±5C. Table 2 shows how theprocess reduces solvent use.
  • 22
  • N,N,N',N'-tetrakis(chloroethyl)chlorophosphorous diamide [ No CAS ]
  • [ 39070-14-9 ]
  • C13H22Cl4N5O3P [ No CAS ]
  • 23
  • [ 39070-14-9 ]
  • [ 1092554-28-3 ]
YieldReaction ConditionsOperation in experiment
82% With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 60℃; for 2.5h;Inert atmosphere; To astirred solution of the imidazole 5 (6.01 g, 38.2 mmol) in anhydrousDMF (45 mL) was added N-bromosuccinimide (7.56 g, 42.5 mmol). Thereaction mixture was stirred at 60 C for 2 h 30. The resulting mixturewas cooled to rt and the reaction was stopped by addition of water(250 mL). The yellow/green solid was filtrated and washed with diethylether (3 × 30 mL). The solid was dried at 30 C under vacuum to yieldthe brominated compound 16 analytically pure (5.84 g, 24.7 mmol).The organic layer of the filtrate was separated and the aqueous layerwas saturated using sodium chloride and extracted with ethyl acetate(2 × 200 mL). The organic layers were combined, washed with brine(500 mL) and water (500 mL) dried over magnesium sulfate, filtratedand evaporated under reduced pressure. The resulting yellow/greensolid was dried at 30 C under vacuum to yield a second fraction ofproduct 16 (1.54 g, 6.52 mmol) analytically pure by 1H and 13C NMRanalysis. Yield 82%; mp 163-164 C; Rf 0.82 (SiO2, AcOEt/cyclohexane,80/20, v/v); IR (ATR) nu cm-1 3321, 1488, 1364, 1015; 1HNMR (500 MHz, DMSO-d6) delta 4.51 (s, 2H, OCH2); 3.98 (s, 3H, NArCH3);13C NMR (126 MHz, DMSO-d6) delta 144.31 (CArNO2); 135.77 (CArCH2);113.92 (CArBr); 52.02 (OCH2); 35.06 (NArCH3).
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 60℃; for 3h; Example 1 : Synthesis of HAP Compounds of the Present Invention A. Synthesis of Compound 14[0090] Example IA describes the synthesis of Compound 14, a HAP compound of the present invention, according to the novel synthetic method of the present invention described above, starting from l-methyl-4-bromo-2-nitroimidazole methanol.[0091] To a solution of Compound i (1 g) in DMF (15 mL) was added N-bromosuccinimide (NBS, 1.25 g) and the reaction mixture stirred at 6O0C for 3 h. Then, the reaction mixture was diluted with brine, extracted with EtOAc, the EtOAc portion dried, and concentrated to yield a residue that was separated by column chromatography using 0 - 80% EtOAc/Hexanes to yield Compound ii (1.3 g). <n="35"/>Compound 14[0092] A solution of l-methyl-4-bromo-2-nitroimidazolemethanol (compound (ii), 3 g) in dimethylformamide (DMF, 100 mL) was degassed by evacuation and purged three times with argon. Tetrakis triphenylphosphine (1.47 g) was added to the reaction mixture and the ensuing solution purged with argon followed by the addition of vinyl tributyltin (11.1 mL). The solution was again purged with argon and the reaction mixture was heated to 110 0C and stirred under argon for 16 h. The solution was cooled and diluted with water (100 mL), filtered through celite, and the celite pad washed twice with hexanes. The aqueous portion of the filtrate was diluted with saturated aqueous NaCl (100 mL) and extracted with EtOAc (250 mL) four times. The combined organic portions was washed twice with brine, dried over MgSO, and separated by column chromatography on silica gel using EtOAc/Hexane (0-100%) as eluent to yield compound (ii) (479 mg) as yellow crystals that was used in the next step.[0093] Bu2Sn(OAc)2 (50 muL) was added to a solution of compound (iii) (470 mg) in dichloromethane (DCM, 12.5 mL) at 0 0C followed by the addition of MeNCO (197 muL). The initial suspension became a solution that was allowed to warm to rt (2 h) then evaporated until dry and the residue was separated by column chromatography on silica gel using EtOAc/Hexanes (0 -100%) as eluent to yield compound (567 mg) as a yellow powder that was used in the next step. [0094] A solution Of OsO4 (427 mL) and deionized water (10 mL) was added to a solution of compound (iv) (322 mg) in dioxane (10 mL) followed by the addition OfNaIO4 (860 mg) in <n="36"/>portions and stirred at room temperature (rt) for 3 h. The reaction mixture was evaporated under vacuo to yield a residue to which was added water (20 mL) and extracted with DCM (30 mL) four times. The DCM solution was dried over NaSO4 and evaporated to dryness. The residue was co-evaporated with absolute EtOH (10 mL), taken up in absolute EtOH (10 mL), and cooled to 0 0C. NaBH4 (56 mg) was added and the solution was stirred for 1 h. Acetone (1 mL) and silica (2 g) were added and the reaction mixture and the adsorbed reaction mixture separated by column chromatography on silica gel using MeOH/DCM (5%) as eluent to yield compound (v) (282 mg) as a colorless solid that was used in the next step.[0095] SOCl2 was added to a solution of compound (v) (49 mg) suspended in DCM (1 mL) at 0 0C. The solution was allowed to warm to rt (40 min), poured into ice water (50 mL), and extracted with EtOAc (50 mL). The organic portion was washed with brine and evaporated to dryness and the residue was separated by chromatography on silica gel using EtOAc/Hexanes (0:100%) as eluent to yield Compound 14 (27.3 mg) as a colorless solid. 1H-NMR (CDCl3): delta 5.20 (s, 2H), 4.72 (s, IH), 4.71 (s, 2H), 4.06 (s, 3H), 2.93 (d, J= 4.8, 3H).
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 60℃; for 3h; To a solution of Compound i (1 g) in DMF (15 mL) was added N- bromosuccinimide (NBS, 1.25 g) and the reaction mixture stirred at 600C for 3h. Then the reaction mixture was diluted with brine, extracted with EtOAc, dried and concentrated to yield a residue that was separated by column chromatography using 0 - 80% EtOAc/Hexanes to yield Compound ii (1.3 g).
  • 24
  • [ 39070-14-9 ]
  • [ 1092554-33-0 ]
  • 25
  • [ 39070-14-9 ]
  • [ 1092554-37-4 ]
  • 26
  • [ 39070-14-9 ]
  • [ 1130010-91-1 ]
  • 27
  • [ 39070-14-9 ]
  • [ 1130011-24-3 ]
  • 28
  • [ 39070-14-9 ]
  • [ 1130010-97-7 ]
  • 29
  • [ 39070-14-9 ]
  • [ 1130010-85-3 ]
  • 30
  • [ 39070-14-9 ]
  • [ 1130010-96-6 ]
  • 31
  • [ 39070-14-9 ]
  • [ 1130011-25-4 ]
  • 32
  • [ 39070-14-9 ]
  • [ 1130011-26-5 ]
  • 33
  • [ 39070-14-9 ]
  • [ 1130011-27-6 ]
  • 34
  • [ 39070-14-9 ]
  • [ 304015-66-5 ]
  • 35
  • [ 39070-14-9 ]
  • [ 304016-33-9 ]
  • 36
  • [ 39070-14-9 ]
  • (1-methyl-2-nitro-1H-imidazol-5-yl)methyl (Z)-3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-5-fluoro-2-oxoindoline-1-carboxylate [ No CAS ]
  • 37
  • [ 39070-14-9 ]
  • 4-((((1-methyl-2-nitro-1H-imidazol-5-yl)methoxy)carbonyl)amino)benzyl (Z)-3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-5-fluoro-2-oxoindoline-1-carboxylate [ No CAS ]
  • 38
  • [ 39070-14-9 ]
  • (1-methyl-2-nitro-1H-imidazol-5-yl)methyl (4-(((6,7-bis(2-methoxyethoxy)quinazolin-4-yl) (3-ethynylphenyl)amino)methyl)phenyl)carbamate [ No CAS ]
  • 39
  • [ 40361-77-1 ]
  • [ 39070-14-9 ]
  • 40
  • [ 40361-79-3 ]
  • [ 39070-14-9 ]
YieldReaction ConditionsOperation in experiment
73% With boron; lithium hydride; In tetrahydrofuran; methanol; at 0℃; for 1h; Dissolve 1-methyl-2-nitro-1H-imidazole-5-carboxylic acid methyl ester 1c (50g, 0.27mol) in 500mL tetrahydrofuran, dropwise add methanol (13g, 0.4mol, 1.5eq), boron at 0 C A solution of lithium hydride in tetrahydrofuran (2M, 202 mL, 1.5 eq) was added, and the reaction was incubated at 0 C for 1 hour.The reaction solution was quenched by adding 500 mL of water, and extracted with ethyl acetate (500 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was added with dichloromethane (200 mL) and filtered to obtain 1-methyl-2-nitro-1H-imidazole-5-methanol 1d (31 g, 0.2 mol, yellow solid), yield: 73%.
  • 41
  • C22H25F2N3O8 [ No CAS ]
  • [ 100-46-9 ]
  • [ 39070-14-9 ]
  • C34H38F2N7O12P [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 2: To a solution of compound G2 (3.41mmol) in THF cooled to -12C was added dropwise phosphorus oxychloride (5.12 mmol). The reaction mixture was stirred at -12C for 40minutes and then, proton sponge (13.64mmol) was added. The reaction mixture was stirred at -12C overnight. To this stirred reaction mixture was added a solution of benzylamine (3.75mmol) and triethylamine (17.05mmol) in acetonitrile (7mL).The reaction mixture was then allowed to warm to -5C. The reaction mixture was stirred for 5 hours. The reaction was monitored by LC/MS. To the reaction mixture was then added a solution of (3-methyl-2-nitro-3H-imidazol-4-yl)-methanol (10.23mmol) and 4-(dimethylamino)pyridine (10.23 mmol) in acetonitrile (10 mL). The reaction mixture was stirred at room temperature overnight, and then concentrated under reduced pressure. The crude residue was partitioned between a 5% solution of citric acid and ethyl acetate. The organic layer was washed with water and brine, dried over over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (DCM/methanol: 0 to 3%) to afford the expected compound G3.
  • 43
  • [ 39070-14-9 ]
  • 1-(1-methyl-2-nitro-1H-imidazol-5-yl)ethan-1-ol [ No CAS ]
  • 44
  • [ 39070-14-9 ]
  • (4-methoxy-3-(1-(1-methyl-2-nitro-1H-imidazol-5-yl)ethoxy)phenyl)(3,4,5-trimethoxyphenyl)methanone [ No CAS ]
  • 45
  • [ 203448-32-2 ]
  • [ 39070-14-9 ]
  • (4-methoxy-3-((1-methyl-2-nitro-1H-imidazol-5-yl)methoxy)phenyl)(3,4,5-trimethoxyphenyl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With triphenylphosphine; In dichloromethane; at 20℃; for 24h;Inert atmosphere; Phenstatin (0.500 g, 1.57 mmol), <strong>[39070-14-9](1-methyl-2-nitro-1H-imidazol-5-yl)methanol</strong> (0.296 g, 1.89 mmol), and DIAD (0.40 mL, 2.04 mmol) were dissolved in CH2Cl2. Triphenylphosphine (0.825 g, 3.14 mmol) was added to the mixture, and the reaction mixture was stirred for 24 h. The reaction mixture was then evaporated under reduced pressure. Flash chromatography of the crude product using a prepacked 100 g silica column [eluents: solvent A: EtOAc; solvent B: hexanes; gradient, 17%A/83%B over 1.19 min (1 CV), 17%A/83%B 100%A/0%B over 8.33 min (7 CV), 100%A / 0%B over 5.95 min (5 CV); flow rate 100 mL/min; monitored at 254 and 280 nm] yielded (4-methoxy-3-((1-methyl-2-nitro-1H-imidazol-5-yl)methoxy)phenyl)(3,4,5-trimethoxyphenyl)methanone (31) as a pale yellow-white solid (0.346 g, 0.757 mmol, 48%) [0.284 g, 0.621 mmol, 39%, corrected for EtOAc].1H NMR (600 MHz, CDCl3) delta 7.62 (1H, d, J = 1.7 Hz), 7.52 (1H, dd, J = 8.3, 1.7 Hz), 7.24 (1H, s), 7.04 (2H, s), 6.97 (1H, d, J = 8.4 Hz), 5.18 (2H, s), 4.16 (3H, s), 3.97 (3H, s), 3.96 (3H, s), 3.91 (6H, s).13C NMR (151 MHz, CDCl3) delta 194.16, 153.97, 152.91, 146.74, 141.88, 132.92, 132.30, 130.43, 129.31, 127.00, 116.43, 110.61, 107.52, 99.98, 61.24, 61.01, 56.39, 56.05, 34.54.HRMS [M+Na]+: 480.1376 (calcd for [C22H23N3NaO8]+,480.1377).HPLC retention time (Method B): 4.66 min [100% at 254 nm].
  • 46
  • ((6S,7aR)-6-allyl-7a-((S)-1-(2-fluoro-5-hydroxy-4-methoxyphenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one) [ No CAS ]
  • [ 39070-14-9 ]
  • (6S,7aR)-6-allyl-7a-((S)-1-(2-fluoro-4-methoxy-5-((l-methyl-2-nitro-1H-imidazol-5-yl)methoxy)phenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 2.5h; A mixture of 5 (200 mg, 0.552 mmol), <strong>[39070-14-9](1-methyl-2-nitro-1H-imidazol-5-yl)methanol</strong> prepared by the procedure described in the patent (Matteucci, M.; Duan, J.-X.; Jiao, H.; Kaizerman, J.; Ammons, S. Phosphoramidate alkylator prodrugs and their preparation, pharmacokinetics and use in the treatment of cancer and hyperproliferative diseases. WO2007002931A2, 2007) (170 mg, 1.10 mmol), and triphenylphosphine (290 mg, 1.10 mmol) in anhydrous THF (15 mL) was cooled to 0 C. in an ice-H2O bath. Diisopropyl azodicarboxylate (220 mg, 1.10 mmol) was then added in a dropwise manner, the ice-bath removed, and the reaction mixture allowed to stir at room temperature for 2.5 h. After this time, the reaction was concentrated under reduced pressure and the crude residue purified by silica gel chromatography (0-15% ethyl acetate/dichloromethane) to afford 108 (250 mg, 89%) as a yellow solid. Compound 108 ((6S,7aR)-6-allyl-7a-((S)-1-(2-fluoro-4-methoxy-5-((l-methyl-2-nitro-1H-imidazol-5-yl)methoxy)phenyl)propan-2-yl)-7,7a-dihydrobenzo[d][1,3]dioxol-5(6H)-one). 1H NMR (500 MHz, CD3OD): delta 7.10 (s, 1H), 6.87 (d, J=7.5 Hz, 1H), 6.81 (d, J=11.5 Hz, 1H), 5.92-5.84 (m, 1H), 5.64 (s, 1H), 5.60 (s, 1H), 5.50 (s, 1H), 5.17-5.09 (m, 4H), 4.11 (s, 3H), 3.81 (s, 3H), 3.03 (dd, J=14.0, 4.0 Hz, 1H), 2.85-2.81 (m, 1H), 2.62 (d, J=14.0 Hz, 1H), 2.58 (dd, J=10.0, 3.5 Hz, 1H), 2.54-2.49 (m, 1H), 2.25-2.18 (m, 1H), 2.11 (dd, J=14.0, 4.0 Hz, 1H), 2.04-2.00 (m, 1H), 0.80 (d, J=7.0 Hz, 3H). ESI MS (Positive Mode) m/z 502 [C25H28FO7+H]+
  • 47
  • [ 39070-14-9 ]
  • C30H25N7O7 [ No CAS ]
  • 48
  • [ 39070-14-9 ]
  • C12H11N3O4 [ No CAS ]
  • 49
  • [ 39070-14-9 ]
  • C25H17N5O4 [ No CAS ]
  • 50
  • [ 39070-14-9 ]
  • C10H17N5O4*C2HF3O2 [ No CAS ]
  • 51
  • [ 229496-07-5 ]
  • [ 5070-13-3 ]
  • [ 39070-14-9 ]
  • (1-methyl-2-nitro-1H-imidazol-5-yl)methyl methyl(2-(methyl(trityl)amino)ethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% To a stirred solution of compound 8 (30mg, 0.19mmol) and DIPEA (49mg, 0.38mmol) in DCM (5mL) was added bis(4-nitrophenyl)carbonate (64mg, 0.21mmol). The reaction was stirred for 4hat room temperature, then was added N,N'-dimethyl-N-tritylethane-1,2-diamine (94mg, 0.29mmol). The mixture was stirred for another 1h. Then the solution was washed with Na2CO3 and extracted with DCM. The combined organic layers were dried over Na2SO4. Concentration was purified by column chromatography on silica gel (heptane: EtOAc=2: 1) to afford compound 17 (88mg, 91%) as yellow solid. mp 100-102C. 1H NMR (400MHz, CDCl3) delta 7.50-7.37 (m, 6H), 7.26-7.19 (m, 6H), 7.18-7.11 (m, 3H), 7.08 (s, 1H), 5.19-5.01 (m, 2H), 4.05-3.62 (m, 3H), 3.56-3.37 (m, 2H), 3.13-2.89 (m, 3H), 2.38-2.18 (m, 2H), 2.18-2.05 (m, 3H). MS (ESI) m/z=514.37 [M+H]+.
  • 52
  • [ 127056-47-7 ]
  • [ 39070-14-9 ]
  • 53
  • [ 141025-16-3 ]
  • [ 39070-14-9 ]
  • (1-methyl-2-nitro-1H-imidazol-5-yl)-N,N-bis(2-bromoethyl)phosphordiamidate [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; To a suspension of N,N'-bis(2-bromoethyl)phosphorodiamidic acid (50mg, 0.16mmol), 1-methyl-2-nitroimidazole-5-methanol (50mg, 0.32mmol), and PPh3 (84mg, 0.32mmol) in THF (15mL) was added DIAD (0.13mL, 0.32mmol) at 0C. After the addition of DIAD, the reaction mixture was warmed to room temperature and stirred overnight. The solvent was removed, and the residue was purified by column chromatography on silica gel (DCM: MeOH=50:1) to afford compound 14 (37mg, 51%) as yellow gum. 1H NMR (400MHz, DMSO) delta 7.25 (s, 1H), 5.05-4.99 (m, 2H), 4.98 (d, J=7.6Hz, 2H), 3.94 (s, 3H), 3.42 (t, J=6.9Hz, 4H), 3.17-3.05 (m, 4H). 13C NMR (101MHz, DMSO) delta 146.1, 134.1(d, J=8.0Hz), 128.2, 55.7 (d, J=4.3Hz), 42.7, 34.3, 34.1 (d, J=5.0Hz). HRMS (ESI): m/z Calcd for C9H17Br2N5O4P, [M+H]+: 469.9204, found: 469.9186.
  • 54
  • 2-azido-5-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1H-imidazole [ No CAS ]
  • [ 39070-14-9 ]
  • 55
  • (2-azido-1-methyl-1H-imidazol-5-yl)methanol [ No CAS ]
  • [ 39070-14-9 ]
  • 56
  • (2-amino-1-methyl-1H-imidazol-5-yl)methanol [ No CAS ]
  • [ 39070-14-9 ]
YieldReaction ConditionsOperation in experiment
61% Compound 12 (4.0g, 31.5mmol) was dissolved in fluoboric acid (40% w/v, 20mL). The solution was cooled to-15C, and a solution of sodium nitrite (3.3g, 47.3mmol) in water (10mL) was added dropwise. The solution was stirred at-15C for 30min, then added dropwise into a solution of Cu powder (2.0g, 119mmol) and sodium nitrite (21.7g, 157.5mmol) in water (50mL). The reaction mixture was stirred at room temperature for 1h. The solution was extracted with EtOAc. The organic extract was evaporated in vacuum, and the residue was eluted by DCM to afford compound 8 (3.0g, 61%) as yellow solid. mp 142-144C. 1H NMR (400MHz, DMSO) delta 7.11 (s, 1H), 5.47 (t, J=5.4Hz, 1H), 4.54 (d, J=5.4Hz, 2H), 3.92 (s, 3H). 13C NMR (101MHz, DMSO) delta 145.7, 138.7, 126.6, 53.0, 34.1. HRMS (ESI): m/z Calcd for C5H8N3O3, [M+H]+: 158.0487, found: 158.0560.
  • 57
  • [ 39070-14-9 ]
  • C33H35N7O10 [ No CAS ]
  • 58
  • [ 39070-14-9 ]
  • C27H25N5O7 [ No CAS ]
  • 59
  • [ 39070-14-9 ]
  • C10H17N5O4*C2HF3O [ No CAS ]
  • 60
  • [ 75-44-5 ]
  • [ 55490-98-7 ]
  • [ 39070-14-9 ]
  • (2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)carbamic acid (3-methyl-2-nitro-3Himidazol-4-yl)methyl ester [ No CAS ]
  • 61
  • [ 75-44-5 ]
  • [ 130001-49-9 ]
  • [ 39070-14-9 ]
  • (2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)carbamic acid (3-methyl-2-nitro-3H-imidazol-4-ylmethyl) ester [ No CAS ]
  • 62
  • [ 39070-14-9 ]
  • [ 184475-71-6 ]
  • N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[(1-methyl-2-nitro-1H-imidazol-5-yl)methoxy]quinazolin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With N-ethyl-N,N-diisopropylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 20℃; for 5h;Cooling with ice; A mixture of 4- (3-chloro-4-fluoroanilino) -6-hydroxy-7-methoxyquinazoline (1) (64 mg, 0.2 mmol)<strong>[39070-14-9]1-methyl-2-nitro-5-hydroxymethylimidazole</strong> (7) (32 mg, 0.2 mmol) andTriphenylphosphine (105 mg, 0.4 mmol)Was dissolved in DMF (3 mL)N, N-diisopropylethylamine (DIEA, 52 mg, 0.4 mmol) was added under ice-To be completed, room temperature reaction 5h.Treatment: DMF was removed under reduced pressure and the residue was extracted with water and dichloromethane (1: 1 by volume)The organic phase was collected and separated by column chromatography to give a white solid59%
  • 63
  • [ 32315-10-9 ]
  • C29H37N3O4Si [ No CAS ]
  • [ 39070-14-9 ]
  • C35H42N6O8Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% To a solution of triphosgene (83 mg, 0.27 mmol) in DCM (10 mL) at 25 C was added a solution of Et3N (181 mg, 1.8 mmol) and compound A10 (prepared as described in: WO 2017/059289; 287 mg, 0.41 mmol) in DCM (10 mL). After stirring for 30 min at 25 C, a solution of <strong>[39070-14-9](1-methyl-2-nitro-1H-imidazol-5-yl)methanol</strong> (102 mg, 0.65 mmol) and Et3N (181 mg, 1.8 mmol) in DMF (5 mL) was added. After stirring 1 h at 25 C, the reaction mixture was partitioned between water (150 mL) and EtOAc (2 x 150 mL). The combined organic layers were dried over MgSO4, filtered, and were concentrated under reduced pressure. Purification of the residue by flash column chromatography (0 to 6% CH3OH in DCM) provided A11 (287 mg, 69%) as a yellow/orange foam. LCMS (condition B): RT = 1.55 min, m/z = 703.5 [M+H]+.
  • 64
  • [ 32315-10-9 ]
  • tert-butyl (5-((5-(5-amino-4-((S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-4-methylenepyrrolidine-1-carbonyl)-2-methoxyphenoxy)pentyl)oxy)-2-((S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-4-methylenepyrrolidine-1-carbonyl)-4-methoxyphenyl)carbamate [ No CAS ]
  • [ 39070-14-9 ]
  • C56H85N7O14Si2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% A solution of triphosgene (62 mg, 0.21 mmol) in DCM (4.0 mL) was added to a stirred solution of A13 (prepared as described in: WO 2013/055987; 500 mg, 0.52 mmol) and Et3N (120 mg, 1.18 mmol) in DCM (20 mL) at 22 C. The mixture was stirred at that temperature for 2 h. A solution of <strong>[39070-14-9](1-methyl-2-nitro-1H-imidazol-5-yl)methanol</strong> (112 mg, 0.71 mmol) in DCM (1 mL) was then added, followed by nBu2Sn(OAc)2 (3 drops). The resulting solution was stirred at 22 C for 16 h under N2 then was concentrated under reduced pressure. The residue was purified by prep-TLC (DCM/MeOH = 30/1) to give A14 as a yellow solid (180 mg, 31%). LCMS (condition A): RT = 1.11 min, m/z = 1136.9 [M+H]+.
  • 65
  • [ 39070-14-9 ]
  • C29H28N6O8 [ No CAS ]
  • 66
  • [ 39070-14-9 ]
  • C29H26N6O8 [ No CAS ]
  • 67
  • [ 39070-14-9 ]
  • C44H57N7O14 [ No CAS ]
  • 68
  • [ 39070-14-9 ]
  • C44H53N7O14 [ No CAS ]
  • 69
  • [ 39070-14-9 ]
  • C39H43N7O11 [ No CAS ]
  • 70
  • C22H32N2O5Si [ No CAS ]
  • [ 39070-14-9 ]
  • C27H39N5O8Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With triethylamine; In dichloromethane; N,N-dimethyl-formamide; at 25℃; for 2h; To a solution of A5 (63.8 mg, 0.15 mmol) in DCM (5.0 mL) was added a solution of <strong>[39070-14-9](1-methyl-2-nitro-1H-imidazol-5-yl)methanol</strong> (46.4 mg, 0.30 mmol) and Et3N (44.8 mg, 0.44 mmol) in DMF (10 mL) at 25 C. The mixture was stirred at 25 C for 2 h. The mixture was concentrated and purified by prep-TLC (5% MeOH in DCM, Rf = 0.5) to give A6 (70 mg, 69%) as a yellow solid. LCMS (condition A): RT = 1.02 min, m/z = 590.2 [M+H]+.
  • 71
  • C4H10Br2ClN2OP [ No CAS ]
  • [ 39070-14-9 ]
  • N,N’-bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester [ No CAS ]
  • 72
  • C10H15Br2Cl2N2P [ No CAS ]
  • [ 39070-14-9 ]
  • (1-methyl-2-nitro-1H-imidazol-5-yl)methyl N,N-bis((2-bromoethyl)prop-2-yn)phosphordiamidate [ No CAS ]
  • 73
  • C23H16N6O4 [ No CAS ]
  • [ 39070-14-9 ]
  • C28H23N9O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.75 g In dichloromethane; at 25℃; for 5h;Cooling with ice; The resulting solid N9-(2-(N-phthalimido)ethyl)-O6-benzyl guanine (2.4 g, 5.8 mmol) dissolved in 10 mL anhydrous dichloromethane,After adding 5 mL of anhydrous pyridine, stir well and weigh up to three bottles of phosgene (0.95 g, 3.2 mmol).Add 18 mL of dichloromethane to dissolve in an ice bath,N9-(2-(N-phthalimido)ethyl) under nitrogen protection conditions-O6-benzyl guanine solution was added dropwise to triphosgene solution.Ice bath 5h,Add 10 mL of dichloromethane solution containing 3-methyl-2-nitroimidazole-4-methanol (1.66 g, 10.6 mmol).The mixture was slowly warmed to 25C for 5 hours. The solvent was distilled off under reduced pressure at 30C, and the residue was purified by silica gel column chromatography.The eluents were petroleum ether and ethyl acetate, gradient elution,The volume ratio of petroleum ether/ethyl acetate gradually increased from 1:1 to 1:4.Vacuum dried at 30C to give a white solidN2-(((3-methyl-2-nitroimidazol)oxy)carbonyl)-N9-(2-(N-phthalimido)ethyl)-O6-benzyl guanine (2.75 g, 4.6 mmol), yield 79%.
  • 74
  • [ 51-28-5 ]
  • [ 39070-14-9 ]
  • 5-(2,4-dinitrophenoxymethyl)-1-methyl-2-nitro-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; at 20℃;Cooling with ice; 2,4-Dinitrophenol (wetted with ca. 20% water, from TCI America, Cat. No. DO 109) (269 mg wet weight, 215 mg dry weight, 1.17 mmol) is dissolved in methylene chloride (2 mL) and stirred with anhydrous sodium sulfate at room temperature for 3 hours. The methylene chloride solution is decanted into a reaction flask and the sodium sulfate is washed with additional methylene chloride (2 mL). To the solution is added (l-methyl-2-nitro-lH-imidazol- 5-yl) methanol (115 mg, 0.732 mmol, prepared by the procedure described in US 8,003,625 B2) and triphenylphosphine (211 mg, 0.805 mmol). The mixture is stirred at room temperature until a solution is achieved. The solution is then cooled in an ice bath and treated with diisopropyl azodicarboxylate, DIAD (158 xL, 0.805 mmol). After 1 hour the ice bath is removed and the mixture is stirred overnight at room temperature. Crude product is purified on a silica gel column to isolate the product mixed with triphenylphosphine oxide. The solids are triturated with t-butyl methyl ether to remove the triphenylphosphine oxide to afford 5-[(2,4- dinitrophenoxy)methyl]-l-methyl-2-nitro-lH-imidazole (70 mg, 0.236 mmol, 30% yield). 1H NMR (DMSO-d6) delta 8.80 (d, J= 2.4 Hz, 1 H), 8.58 (dd, J= 9.6, 2.4 Hz, 1 H); delta 7.82 (D, J= 9.6 Hz, 1 H), 7.40 (s, 1 H), 5.66 (s, 2 H), 3.95 (s, 3 H). MS (ESI+) for C11H9N5O7 m/z 324.1 (M+H)+.
  • 75
  • [ 100-02-7 ]
  • [ 39070-14-9 ]
  • 1-methyl-2-nitro-5-(4-nitrophenoxymethyl)-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; at 20℃;Cooling with ice; 4-Nitrophenol (162 mg, 1.17 mmol) is dissolved in methylene chloride (2 mL). To the solution is added (3-methyl-2-nitro-3H-imidazol-4-yl)-methanol (115 mg, 0.732 mmol) and triphenylphosphine (211 mg, 0.805 mmol). The mixture is stirred at room temperature until a solution is achieved. The solution is then cooled in an ice bath and treated with diisopropyl azodicarboxylate, DIAD (158 uL, 0.805 mmol). After 1 hour the ice bath is removed and the mixture is stirred overnight at room temperature. Crude product is purified on a silica gel column to isolate the product mixed with triphenylphosphine oxide. The solids are triturated with t-butyl methyl ether to remove the triphenylphosphine oxide to afford l-methyl-2-mtro-5- (4-nitro-phenoxymethyl)-lH-imidazole. MS (ESI+) for C11H10N4O5 m/z 279.1 (M+H)+.
  • 76
  • [ 618-80-4 ]
  • [ 39070-14-9 ]
  • 5-(2,6-dichloro-4-nitrophenoxymethyl)-1-methyl-2-nitro-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; at 20℃;Cooling with ice; 2,6-Dichloro-4-nitro-phenol (243 mg, 1.17 mmol) is dissolved in methylene chloride (2 mL). To the solution is added (3-methyl-2-nitro-3H-imidazol-4-yl)-niethanol (115 mg, 0.732 mmol) and triphenylphosphine (211 mg, 0.805 mmol). The mixture is stirred at roomtemperature until a solution is achieved. The solution is then cooled in an ice bath and treated with diisopropyl azodicarboxylate, DIAD (158 mu,, 0.805 mmol). After 1 hour the ice bath is removed and the mixture is stirred overnight at room temperature. Crude product is purified on a silica gel column to isolate the product mixed with triphenylphosphine oxide. The solids are triturated with t-butyl methyl ether to remove the triphenylphosphine oxide to afford 5-(2,6- dichloro-4-nitro-phenoxymethyl)- 1 -methyl-2-nitro- IH-imidazole. MS (ESI+) for C11H8Cl2N4O5 m/z 347.0 (M+H)+.
  • 77
  • [ 586-11-8 ]
  • [ 39070-14-9 ]
  • 5-(3,5-dinitrophenoxymethyl)-1-methyl-2-nitro-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; at 20℃;Cooling with ice; 3,5-Dinitro-phenol (215 mg, 1.17 mmol) is dissolved in methylene chloride (2 mL). To the solution is added (3-methyl-2-nitro-3H-imidazol-4-yl)-methanol (115 mg, 0.732 mmol) and triphenylphosphine (211 mg, 0.805 mmol). The mixture is stirred at room temperature until a solution is achieved. The solution is then cooled in an ice bath and treated with diisopropyl azodicarboxylate, DIAD (158 mu-,, 0.805 mmol). After 1 hour the ice bath is removed and the mixture is stirred overnight at room temperature. Crude product is purified on a silica gel column to isolate the product mixed with triphenylphosphine oxide. The solids are triturated with t-butyl methyl ether to remove the triphenylphosphine oxide to afford 5-(3,5-dinitro- phenoxymethyl)-l-methyl-2-nitro-lH-imidazole. MS (ESI+) for C11H9N5O7 m/z 324.1 (M+H)+.
  • 78
  • [ 120-83-2 ]
  • [ 39070-14-9 ]
  • 5-(2,4-dichlorophenoxymethyl)-1-methyl-2-nitro-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In dichloromethane; at 20℃;Cooling with ice; 2,4-Dichloro-phenol (190 mg, 1.17 mmol) is dissolved in methylene chloride (2 mL). To the solution is added (3-methyl-2-nitro-3H-imidazol-4-yl)-methanol (115 mg, 0.732 mmol) and triphenylphosphine (211 mg, 0.805 mmol). The mixture is stirred at room temperature until a solution is achieved. The solution is then cooled in an ice bath and treated with diisopropyl azodicarboxylate, DIAD (158 xL, 0.805 mmol). After 1 hour the ice bath is removed and the mixture is stirred overnight at room temperature. Crude product is purified on a silica gel column to isolate the product mixed with triphenylphosphine oxide. The solids are triturated with t-butyl methyl ether to remove the triphenylphosphine oxide to afford 5-(2,4-dichloro- phenoxymethyl)-l-methyl-2-nitro-lH-imidazole. MS (ESI+) for C11H9Cl2N3O3m/z 301.1 (M+H)+.
  • 79
  • [ 350-46-9 ]
  • [ 39070-14-9 ]
  • [ 60768-31-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Heating; A mixture of 2-(l-methyl-5-nitro-lH-imidazol-2-yl)-ethanol (1.24 mmol) and 1-fluoro- 4-nitrobenzene (1.45 mmol) and K2C03(465 mg, 3.36 mmol) in DMF (5 mL) was stirred 2 hours at ambient temperature followed by heating. The reaction was worked-up by extraction. The residue was purified by prep-HPLC with the following condition: column: XBridge preparative C18 OBD column 19x150 mm, 5 um; mobile phase A: water (10 mmol/L NH4HC03), mobile phase B: ACN; flow rate: 20 mL/min; gradient elution. The product-containing fractions were collected and then lyophilized to give l-memyl-5-nitro-2-(4-nitro-phenoxymethyl)-lH- imidazole. LC-MS: (ES, m/z) 279.07 (M+H)+; analysis: C, 47.35; H, 3.71; N, 20.24; O, 28.82.
  • 80
  • [ 402-67-5 ]
  • [ 39070-14-9 ]
  • [ 60768-34-5 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Heating; A mixture of 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-ethanol (1.32 mmol) and 1-fluoro- 3 -nitrobenzene (1.67 mmol) and K2C03(465 mg, 3.36 mmol) in DMF (5 mL) was stirred 2 hours at ambient temperature followed by heating. The reaction was worked-up by extraction. The residue was purified by prep-HPLC with the following condition: column: XBridge preparative CI 8 OBD column 19x 150 mm, 5 um; mobile phase A: water (10 mmol/L NH4HCO3), mobile phase B: ACN; flow rate: 20 mL/min; gradient elution. The product-containing fractions were collected and then lyophilized to give l-methyl-5-nitro-2-(3-nitro-phenoxymethyl)-lH- imidazole. LC-MS: (ES, m/z) 279.07 (M+H)+; analysis: C, 47.53; H, 3.69; N, 20.24; O, 28.85.
  • 81
  • [ 1435-48-9 ]
  • [ 39070-14-9 ]
  • 2-(2,4-dichlorophenoxymethyl)-1-methyl-5-nitro-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Heating; A mixture of 2-(l-methyl-5-nitro-lH-imidazol-2-yl)-ethanol (1.25 mmol) and 2,4-di- chloro-l-fluorobenzene (1.45 mmol) and K2C03(465 mg, 3.36 mmol) in DMF (5 mL) was stirred 2 hours at ambient temperature followed by heating. The reaction was worked-up by extraction. The residue was purified by prep-HPLC with the following condition: column:XBridge preparative C18 OBD column 19x150 mm, 5 urn; mobile phase A: water (10 mmol/L NH4HC03), mobile phase B: ACN; flow rate: 20 mL/min; gradient elution. The product- containing fractions were collected and then lyophilized to give 2-(2,4-dichloro-phenoxymethyl)- l-methyl-5-nitro-lH-imidazole. LC-MS: (ES, m/z) 302.00 (M+H)+; analysis: C, 43.78; H, 3.08; CI, 23.52; N, 13.81; O, 15.99.
  • 82
  • [ 3107-19-5 ]
  • [ 39070-14-9 ]
  • 2-(2,6-dichloro-4-nitrophenoxymethyl)-1-methyl-5-nitro-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Heating; A mixture of 2-( 1 -methyl-5-nitro- 1 H-imidazol-2-yl)-ethanol (1.15 mmol) and 1 ,3- dichloro-2-fluoro-5-nitro-benzene (1.24 mmol) and K2C03(465 mg, 3.36 mmol) in DMF (5 mL) was stirred 2 hours at ambient temperature followed by heating. The reaction was worked-up by extraction. The residue was purified by prep-HPLC with the following condition: column:XBridge preparative C18 OBD column 19x150 mm, 5 um; mobile phase A: water (10 mmol/L NH4HC03), mobile phase B: ACN; flow rate: 20 mL/min; gradient elution. The product- containing fractions were collected and then lyophilized to give 2-(2,6-dichloro-4-nitro- phenoxymethyl)-l-methyl-5-nitro-lH-imidazole. LC-MS: (ES, m/z) 346. (M+H)+; analysis: C, 38.01; H, 2.22; CI, 20.13; N, 16.19; O, 23.15.
  • 83
  • [ 369-18-6 ]
  • [ 39070-14-9 ]
  • 2-(3,5-dinitrophenoxymethyl)-1-methyl-5-nitro-1H-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Heating; A mixture of 2-(l-methyl-5-nitro-lH-imidazol-2-yl)-ethanol (1.22 mmol) and 3,5-di- nitro-l-fluorobenzene (1.54 mmol) and K2C03(465 mg, 3.36 mmol) in DMF (5 mL) was stirred 2 hours at ambient temperature followed by heating. The reaction was worked-up by extraction. The residue was purified by prep-HPLC with the following condition: column: XBridge preparative C18 OBD column 19x 150 mm, 5 um; mobile phase A: water (10 mmol/LNH4HCO3), mobile phase B: ACN; flow rate: 20 mL/min; gradient elution. The product- containing fractions were collected and then lyophilized to give 2-(3,5-dinitro-phenoxymethyl)- l-methyl-5-nitro-lH-imidazole. LC-MS: (ES, m/z) 324.05 (M+H)+; analysis: C, 40.90; H, 2.89; N, 21.72; O, 34.60.
  • 84
  • [ 39070-14-9 ]
  • 5-([bis(2-chloroethyl)amino][(1-methyl-2-nitro-1H-imidazol-5-yl)methoxy]phosphoryl}amino)-N-ethyl-N,N-dimethylpentane-1-aminium iodide [ No CAS ]
  • 85
  • [ 39070-14-9 ]
  • 4-([bis(2-chloroethyl)amino][(1-methyl-2-nitro-1H-imidazol-5-yl)methoxy]phosphoryl}amino)-N-ethyl-N,N-dimethylbutane-1-aminium iodide [ No CAS ]
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