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CAS No. : | 58421-79-7 | MDL No. : | MFCD03665203 |
Formula : | C9H7ClN2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | XNILKVADCMYCQT-UHFFFAOYSA-N |
M.W : | 178.62 | Pubchem ID : | 940217 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.11 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 49.51 |
TPSA : | 25.78 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.35 cm/s |
Log Po/w (iLOGP) : | 2.2 |
Log Po/w (XLOGP3) : | 2.87 |
Log Po/w (WLOGP) : | 2.59 |
Log Po/w (MLOGP) : | 2.16 |
Log Po/w (SILICOS-IT) : | 3.04 |
Consensus Log Po/w : | 2.57 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.37 |
Solubility : | 0.0758 mg/ml ; 0.000424 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.07 |
Solubility : | 0.152 mg/ml ; 0.00085 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.33 |
Solubility : | 0.00837 mg/ml ; 0.0000469 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.28 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With oxalyl dichloride In chloroform; N,N-dimethyl-formamide at 100℃; for 3 h; | Intermediate 10-b (2.1 g, 13.11 mmol) was dissolved in CHC13 (30 ml). Oxalyl chloride(1.97 g, 23.26 mmol) and DMF (0.1 ml) were added. The mixture was heated to 100°C for3 hours. The solvent was evaporated to get intermediate 10 (1.5 g, 58 percent).m/z = 179 (M+H). |
58% | With oxalyl dichloride In chloroform; N,N-dimethyl-formamide at 100℃; for 3 h; | Intermediate 12-b (2.1 g, 13.11 mmol) was dissolved in CHC13 (30 ml). Oxalyl chloride(1.97 g, 23.26 mmol) and DMF (0.1 ml) were added. The mixture was heated to 100°Cfor 3 hours. The solvent was evaporated to get intermediate 12 (1.5 g, 58 percent).m/z = 179 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; trichlorophosphate; In toluene; at 120℃; for 2h; | Example 75; Preparation of Compound 75 A (C-methyl):; [0072] To a mixture of <strong>[19181-53-4]6-methylquinazolin-4(3H)-one</strong> (395 mg, 2.47 mmol), prepared according to literature,1 in 5 mL of dry toluene, was added /-PrEt2N (0.8 mL), followed by POCl3 (3.4 mL). The mixture was heated to 120C for 2 hr. After cooling to room temperature, the volatiles were removed under reduced pressure and the residue was dissolved in CH2Cl2, washed with cold, half-saturated NaHCO3 aq. solution and 5% citric acid and dried over anhydrous MgSO4. Concentration in vacuo gave 415 mg of Compound 75A as a solid. 1H-NMR (400 MHz, CDCl3): 9.00 (s, IH), 8.04 (d, J = 1.86 Hz, IH), 7.98 (d, J = 8.61 Hz, IH), 7.80 (dd, J = 1.86 Hz, J = 8.61 Hz5 IH), 2.62 (s, 3H). | |
With thionyl chloride; N,N-dimethyl-formamide; for 8h;Reflux; | General procedure: A mixture of 4-quinazolone analogues 2a-2j (8.0 mmol) in SOCI2 (27.4 mL) containing DMF (2 drops) was refluxed for 8 h. SOCI2 was removed under reduced pressure and the residue was dissolved in DCM. The solution was washed with saturated NaHCO3 solution and brine, respectively, dried over anhydrous Na2S04 and then concentrated under reduced pressure to yield the compounds 3a-3j (65.1-88.9percent yield) as white or off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | In ethanol; for 1.5h;Heating / reflux; | [[00126]] 270 mg, 1. 5 mM, 4-chloro 6-methyl quinazoline (AG 1474) and 230 mg, 1.6 mM, l-amino naphtalene in 15 ml ethanol were refluxed 1.5 hours. Workup (KOH) and trituration with dichloromethane-hexane gave 267 mg, 62% yield. NMR CDC13 [8] 8.64 [(LH,] s), 7.9-7. 3 [(10H,] m), 2.60 (3H, s, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | In ethanol; for 1.5h;Heating / reflux; | [[00125]] 270 mg, [1] mM, 4-chloro 6-methyl quinazoline (AG 1474) and 270 mg, 1.6 mM, 2-amino biphenyl in 15 ml ethanol were refluxed 1.5 hours. Workup (KOH) and trituration with dichloromethane-hexane gave 210 mg, 45% yield, pink solid. NMR [CDC13] 6 8.70 [(LH,] m), 7. [8-6.] 8 [(12H.] m), 2.40 (3H. s, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | In ethanol; for 1.0h;Heating / reflux; | [[00107]] 307 mg, 1.71 mM, 4-chloro 6=methyl quinazoline (AG 1474) and 216 mg, 1.83 mM, anthranilo nitrile in 10 ml ethanol were refluxed for 1 hour. On cooling no precipitate is formed. The reaction was made basic with aqueous KOH and extracted with [CH2C12.] Evaporation and trituration with [CC14] gave 130 mg, 29% yield, yellow solid, mp-272, as the free base. NMR CDC13 d 8.70 (1H, S, H2), 7.90-7. 60 (6H, m), 7.35 [(LH,] m), 2.50 (3H, S). MS-260 (M+, 18+), 250 (100), 248 (65), m/e. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | In ethanol; for 1.0h;Heating / reflux; | [00100] 230 mg, [1.] 3mM, 4-chloro 6-methyl quinazoline (AG 1474) and 145 mg, [1.] [33] mM, 2-aminophenol in 10 ml ethanol were refluxed for 1 hour. Workup [(H20,] Na2C03, [CH2C12)] and trituration with hexane gave [63] mg, 19% yield, light green solid as the free base, mp-270d. NMR DMSO d6 [8] 8.41 [(1H,] S, H2), 8.27 (1H, S, [H5),] 7.67 (2H, S), 7.54 [(LH,] m), 7.1-6. 8 (3H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; | A. 6-Bromomethyl-4-chloro-quinazoline. A flask containing 4-Chloro-6-methylquinazoline (0.91 g, 5.09 mmol), NBS (0.95 g, 5.35 mmol), benzoyl peroxide 70% (0.09 g, 0.2545 mmol) and carbon tetrachloride (25 mL) is refluxed at 80 C. for 20 h. The solution is cooled to RT, filtered and concentrated. Purification by flash chromatography (7.5% EtOAc/hexanes) yields the title compound as a white solid (0.62 g, 2.42 mmol). 1H NMR (CDCl3, 300 MHz) 9.06 (s, 1H), 8.25 (s, 1H), 8.07 (d, 1H), 8.00 (d, 1H), 4.67 (s, 2H). | |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; | A. 6-Bromomethyl-4-chloro-quinazoline A flask containing 4-Chloro-6-methylquinazoline (0.91 g, 5.09 mmol), NBS (0.95 g, 5.35 mmol), benzoyl peroxide 70% (0.09 g, 0.2545 mmol) and carbon tetrachloride (25 mL) is refluxed at 80 C. for 20 h. The solution is cooled to RT, filtered and concentrated. Purification by flash chromatography (7.5% EtOAc/hexanes) yields the title compound as a white solid (0.62 g, 2.42 mmol). 1H NMR (CDCl3, 300 MHz) 9.06(s, 1H), 8.25(s, 1H), 8.07(d, 1H), 8.00(d, 1H), 4.67(s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | In isopropyl alcohol; | EXAMPLE 3 A mixture of <strong>[58421-79-7]4-chloro-6-methylquinazoline</strong> (0.5 g), 3-methylaniline (0.33 g) and isopropanol (10 ml) was stirred and heated to reflux for 1 hour. The mixture was cooled to ambient temperature. The precipitate was filtered off and washed with cold isopropanol and with diethyl ether. There was thus obtained 6-methyl-4-(3'-methylanilino)quinazoline (0.61 g, 76%), m.p. 243-245 C. NMR Spectrum: (CD3 SOCD3) 2.38 (s, 3H), 2.57 (s, 3H), 7.1-8.0 (m, 6H), 8.77 (s, 1H), 8.88 (s, 1H); Elemental Analysis: Found C, 67.0; H, 5.5; N, 14.5; C16 H15 N3. HCl requires C, 67.2; H, 5.6; N, 14.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | Example 93 4-(6-Chloro-2,3-dihydro-indol-1-yl)-6-methyl-quinazoline Utilizing a procedure analogous to that described in Example 24, this product was prepared in 15% yield from <strong>[52537-00-5]6-chloro-indoline</strong> and 4-chloro-6-methyl-quinazoline. (M.P. 138-41 C.; LC-MS: 296 (MH+)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In chloroform; benzene; | Preparation 2. Compound No. 31 To a solution of 1.8 g (0.01 mol) of <strong>[58421-79-7]4-chloro-6-methylquinazoline</strong> in 50 ml of benzene were added 1.0 g (0.01 mol) of triethylamine and 1.7 g (0.01 mol) of 2-(O-methoxyphenoxy)ethylamine, and the mixture was heated, with stirring, at 60~70 C. for 5 hours. After completion of the reaction, the benzene was evaporated under reduced pressure and the residue was dissolved in chloroform, washed with water and dried over anhydrous sodium sulfate. The chloroform was evaporated under reduced pressure to leave crystals, which were recrystallized from ethanol, giving 0.9 g of 6-methyl-4-[2-(2-methoxyphenoxy)ethyl]-aminoquinazoline in the form of colorless plates. m.p. 167~169 C. Elementary analysis (%): Calcd: C, 69.88; H, 6.19; N, 13.58 Found: C, 69.86; H, 6.15; N, 13.60 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In toluene; | B. 4-Chloro-6-methyl-quinazoline 6-Methyl-3H-quinazolin-4-one (1.1 g, 6.9 mmol) is dissolved in toluene (70 mL). To the solution is added triethyl amine (1.82 g, 18 mmol) and P(O)Cl3 (1.06 g, 6.9 mmol). The solution is heated to reflux. After 3 h, the solution is poured into water (100 mL). The solution is diluted with EtOAc (200 mL). The layers are separated. The organic layer is washed with water, saturated NaHCO3 (aq.) and saturated NaCl (aq.). The organic layer is dried over MgSO4, filtered and concentrated. The title compound is obtained as an oil (0.75 g, 4.2 mmol). 1H NMR (CDCl3, 300 MHz) delta8.98 (s, 1H), 8.04 (s, 1H), 7.98 (d, 1H), 7.82 (d, 1H), 2.62 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.4% | With thionyl chloride; In N,N-dimethyl-formamide; at 85℃; for 6.0h;Inert atmosphere; | A mixture of S1 (9.26g, 57.8mmol), Thionyl chloride (150ml) in DMF (3 ml) wasrefluxed for 6h. Excess SOCl2 was removed under reduced pressure and the residuewas dissolved in the dichloromethane, washed with saturated NaHCO3 aqueoussolution and dried over anhydrous Na2SO4. The solvent was removed under reducedpressure to afford the crude product S2 (10.2g, 98.4%) without further purification. |
58% | With oxalyl dichloride; In chloroform; N,N-dimethyl-formamide; at 100℃; for 3.0h; | Intermediate 10-b (2.1 g, 13.11 mmol) was dissolved in CHC13 (30 ml). Oxalyl chloride(1.97 g, 23.26 mmol) and DMF (0.1 ml) were added. The mixture was heated to 100C for3 hours. The solvent was evaporated to get intermediate 10 (1.5 g, 58 %).m/z = 179 (M+H). |
58% | With oxalyl dichloride; In chloroform; N,N-dimethyl-formamide; at 100℃; for 3.0h; | Intermediate 12-b (2.1 g, 13.11 mmol) was dissolved in CHC13 (30 ml). Oxalyl chloride(1.97 g, 23.26 mmol) and DMF (0.1 ml) were added. The mixture was heated to 100Cfor 3 hours. The solvent was evaporated to get intermediate 12 (1.5 g, 58 %).m/z = 179 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.6% | With potassium carbonate; In acetonitrile; at 30 - 50℃; for 8.0h;Inert atmosphere; | General procedure: A 100mL oven-dried round bottom flask charged with 1.62g (10.0mmol) (E)-4-(2-hydroxy-phenyl)-3-butylene-2-one or 4-(4-hydroxy-phenyl)-3-butylene-2-one, 1.65g (10.0mmol) 4-chloroquinazoline, and 3g potassium carbonate in dry acetonitrile (20mL) was placed at room temperature. The reaction mixture was stirred further for 8h at 30 to 50C. In the reaction mixture, the excess K2CO3 was filtered out, and the solvent was removed by evaporation. The crude product was recrystallized with anhydrous ethanol solvent to yield 75% to 86% of intermediates 4a to 4f. The data for 4a to 4f are shown below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.5% | With potassium carbonate; In acetonitrile; at 30 - 50℃; for 8.0h;Inert atmosphere; | General procedure: A 100mL oven-dried round bottom flask charged with 1.62g (10.0mmol) (E)-4-(2-hydroxy-phenyl)-3-butylene-2-one or 4-(4-hydroxy-phenyl)-3-butylene-2-one, 1.65g (10.0mmol) 4-chloroquinazoline, and 3g potassium carbonate in dry acetonitrile (20mL) was placed at room temperature. The reaction mixture was stirred further for 8h at 30 to 50C. In the reaction mixture, the excess K2CO3 was filtered out, and the solvent was removed by evaporation. The crude product was recrystallized with anhydrous ethanol solvent to yield 75% to 86% of intermediates 4a to 4f. The data for 4a to 4f are shown below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With triethylamine; In isopropyl alcohol; at 65℃;Inert atmosphere; | To a solution of <strong>[58421-79-7]4-chloro-6-methylquinazoline</strong> (75 mg, 0.42 mmol) and 6-fluoro- 1,2,3,4-tetrahydronaphthalen-2-amine (70 mg, 0.42 mmol) in isopropyl alcohol (10 mL) was added triethylamine (127 mg, 1.3 mmol). The resulting solution was heated to 65 C under nitrogen for overnight. LC-MS analysis showed completed consumption of starting material. The reaction mixture was cooled down and excess isopropyl alcohol was removed by rotary evaporation. The residue was purified by Prep-HPLC to give A24-006 as a white solid (60 mg, yield: 46%). LC-MS 420 (M+H), purity 100% (UV 214 nm); ?HNMR (400 MHz, DMSO-d6) oe 8.43 (s, 1 H), 8.15 (s, 1 H), 7.97 (d, J = 7.2 Hz, 1 H), 7.60 (s, 2 H), 7.17-6.94 (m, 3 H), 4.62-4.58 (m, 1 H), 3.18-3.13 (m, 1 H), 2.94-2.85 (m, 3 H), 2.43 (s, 3 H),2.14-2.18 (m, 1 H), 1.88-1.82 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 40℃; for 10.0h; | General procedure: 4-Hydroxychalcone (3 mmol), 4-chloroquinazoline (3 mmol), K2CO3 (6.3 mmol), and acetone (15 mL) were added to an oven-dried one-neck 50 mL round-bottom flask equipped with a magnetic stirring bar. The resulting mixture was stirred at 40 C for 10 h, poured into ice water (40 mL), and then separated. The aqueous phase was acidified with 10% HCl to pH 5-7 and then filtered. The residue was dried and recrystallized from ethanol to obtain compounds 2a-i as white solids [20]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 40℃; for 10.0h; | General procedure: 4-Hydroxychalcone (3 mmol), 4-chloroquinazoline (3 mmol), K2CO3 (6.3 mmol), and acetone (15 mL) were added to an oven-dried one-neck 50 mL round-bottom flask equipped with a magnetic stirring bar. The resulting mixture was stirred at 40 C for 10 h, poured into ice water (40 mL), and then separated. The aqueous phase was acidified with 10% HCl to pH 5-7 and then filtered. The residue was dried and recrystallized from ethanol to obtain compounds 2a-i as white solids [20]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 40℃; for 10.0h; | General procedure: 4-Hydroxychalcone (3 mmol), 4-chloroquinazoline (3 mmol), K2CO3 (6.3 mmol), and acetone (15 mL) were added to an oven-dried one-neck 50 mL round-bottom flask equipped with a magnetic stirring bar. The resulting mixture was stirred at 40 C for 10 h, poured into ice water (40 mL), and then separated. The aqueous phase was acidified with 10% HCl to pH 5-7 and then filtered. The residue was dried and recrystallized from ethanol to obtain compounds 2a-i as white solids [20]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 40℃; for 10.0h; | General procedure: 4-Hydroxychalcone (3 mmol), 4-chloroquinazoline (3 mmol), K2CO3 (6.3 mmol), and acetone (15 mL) were added to an oven-dried one-neck 50 mL round-bottom flask equipped with a magnetic stirring bar. The resulting mixture was stirred at 40 C for 10 h, poured into ice water (40 mL), and then separated. The aqueous phase was acidified with 10% HCl to pH 5-7 and then filtered. The residue was dried and recrystallized from ethanol to obtain compounds 2a-i as white solids [20]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 40℃; for 10.0h; | General procedure: 4-Hydroxychalcone (3 mmol), 4-chloroquinazoline (3 mmol), K2CO3 (6.3 mmol), and acetone (15 mL) were added to an oven-dried one-neck 50 mL round-bottom flask equipped with a magnetic stirring bar. The resulting mixture was stirred at 40 C for 10 h, poured into ice water (40 mL), and then separated. The aqueous phase was acidified with 10% HCl to pH 5-7 and then filtered. The residue was dried and recrystallized from ethanol to obtain compounds 2a-i as white solids [20]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2.0h;Sealed tube; | 4-Chloro-6-methylquinazoline (1020 mg, 5.71 mmol), Cs2CO3 (6512 mg, 19.99 mmol), and tert-butyl (Qrans)-4-aminocyclohexyl)carbamate (1846 mg, 8.61 mmol) were weighed directly into a round bottom flask and dissolved in DMF (28.0 mL). The flask was sealedand its contents were stirred at room temperature for 2 hours. The reaction mixture was filtered through a pad of celiteTM washing through with DMF (10 mL). The reaction mixture was concentrated by reduced pressure. Upon addition of water, a precipitate formed which was collected by vacuum filtration, washed with diethyl ether and dried under reduced pressure to afford the title compound. MS: 357 (M+1). ?H NMR (600 MHz, DMSO-d6) oe8.34 (s, 1H), 8.05 (s, 1H), 7.73 (d, J= 7.9 Hz, 1H), 7.56-7.49 (m, 2H), 6.74 (d, J= 8.0 Hz,1H), 4.12-4.01 (m, 1H), 3.24-3.19 (m, 1H), 2.42 (s, 3H), 1.91 (d, J= 11.7 Hz, 2H), 1.81 (d, J = 11.2 Hz, 2H), 1.46-1.37 (m, 2H), 1.34 (s, 9H), 1.3 1-1 .22 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; N,N-dimethyl-formamide; | 4-Chloro-6-methylquinazoline (60 mg, 0.3 36 mmol) was added to a flask containing sodium hydride (50 mg, 1.250 mmol) and (trans)-4-morpholinocyclohexanol (70 mg, 0.378 mmol). THF (5 ml) and DMF (0.200 ml, 2.58 mmol) were added and the contents of the flask were stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, filtered and was purified by mass triggered reverse phase HPLC (ACN/water with0.1% NH4OH modifier) to afford the title compound as a free base. MS: 328 (M+1). ?H NMR (600 MHz, DMSO-d6) oe 8.67 (s, 1H), 7.85 (s, 1H), 7.77-7.72 (m, 2H), 5.23-5.19 (m, 1H), 3.54 (s, 4H), 2.46-2.41 (m, 7H), 2.26 (br s, 1H), 2.18 (d, J= 11.5 Hz, 2H), 1.88 (d, J=12.1 Hz, 2H), 1.53 (q, J= 11.9 Hz, 2H), 1.48-1.35 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃;Sealed tube; | 4-Chloro-6-methylquinazoline (104 mg, 0.582 mmol), Cs2CO3 (664 mg, 2.038 mmol), and 4-aminocyclohexanone bis-hydrochloride (86 mg, 0.5 75 mmol) were weighed directly into a flask and dissolved in DMF (3000 tl). The flask was sealed and its contents were stirred overnight at room temperature. The reaction mixture was filtered through a pad of celiteTM washing through with approximately 10 mL of DMF. The mixture was concentrated under reduced pressure. The resulting oil was reconstituted in ethyl acetate and washed withsaturated sodium bicarbonate (2x) and brine. The combined aqueous fractions were extracted with ethyl acetate (2x). The combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (0-10% ethyl acetate/methanol) to afford the title compound. MS: 256 (M+1). ?H NMR (600 MHz, DMSO-d6) oe 8.40 (s, 1H), 8.08 (s, 1H),7.83 (d, J= 7.4, 1H), 7.56 (s, 2H), 4.67-4.62 (m, 1H), 2.57-2.50 (m, 2H), 2.43 (s, 3H), 2.27 (d, J= 14.7 Hz, 2H), 2.21-2. 14 (m, 2H), 1.86-1.80 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | With N-ethyl-N,N-diisopropylamine; In 2-methoxy-ethanol; at 80℃; | Intermediate 8 (100 mg, 0.30 mmol) was dissolved in 2-methoxyethanol (3 mL). Then<strong>[58421-79-7]4-chloro-6-methylquinazoline</strong> 10 (78.47 mg, 0.44 mmol, 1.5 eq.) and DIPEA (0.150 mL,0.88 mmol, 3 eq.) were added. The reaction mixture was stirred at 80C during 1 night. The reaction mixture was cooled to room temperature and evaporated under reduce pressure. The crude was purified by reverse phase HPLC to give compound P4 (21 mg, 100 % pure, 15 %yield).LCMS (M+1) = 484.1H NMR (400 MHz, DMSO-d6) oe ppm 1.60 - 1.85 (m, 8 H) 2.00 - 2.14 (m, 1 H) 2.43 (s, 3 H)2.46 (br. s., 1 H) 2.71 (t, J=6.16 Hz, 2 H) 2.80 (t, J=6.60 Hz, 2 H) 3.39 - 3.46 (m, 5 H) 3.66 (t,J=4.18 Hz, 4 H) 4.20 (d, J=12.76 Hz, 1 H) 5.92 (d, J=2.64 Hz, 1 H) 6.31 (s, 1 H) 7.63 (dd, J8.58, 1.54 Hz, 1 H) 7.71 (d, J8.58 Hz, 1 H) 7.87 (s, 1 H) 8.55 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In 2-methoxy-ethanol; at 80 - 90℃; for 17.0h; | Intermediate 66 (250 mg, 0.624 mmol), <strong>[58421-79-7]4-chloro-6-methylquinazoline</strong> 12 (145 mg, 0.811 mmol) and DIPEA (355 tl, 2.058 mmol) were mixed in 2-methoxyethanol(4.2 ml) and heated at 80C for 16 hours and at 90C for 1 hour. After cooling to room temperature, the reaction mixture was added slowly to iced water. The suspension wasstirred at room temperature overnight. The brown precipitate was filtered off, washed with water and then dried in the vacuum oven for 16 hours. The crude of the titleintermediate 67 (250 mg) was used as such in the next step. m/z = 529.4 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | The crude intermediate 19 (150 mg, 0.30 mmol) and <strong>[58421-79-7]4-chloro-6-methylquinazoline</strong> 12 (107 mg, 0.60 mmol) were dissolved in 2-methoxyethanol (3.79 ml) and then diisopropylethyl amine (619 tl, 3.59 mmol) was added. The solution was heated at100C overnight. The heating was stopped and the mixture was cooled to room temperature. To the reaction mixture was added morpholine (1.035 ml, 11.97 mmol) and the mixture was heated at 70C for 3 hours. Then it was evaporated to dryness. The resulting residue was purified by column chromatography eluting with 2.5% (MeOH/NH3) and dichloromethane. The oil obtained was recrystallized in di-isopropylether. The formed off-white crystals were filtered to get intermediate 20 (52 mg, 3 8%). m/z = 444.25 (M+H)MP = 180.64C1H NMR (400 MHz, DMSO-d6) oe ppm 1.57 - 1.80 (m, 4 H) 1.92 - 2.08 (m, 1 H) 2.24(s, 3 H) 2.34-2.46 (m, 4 H) 3.20-3.28 (m, 4 H) 3.45 (br. t, J=11.20, 11.20 Hz, 1 H)3.67 - 3.83 (m, 4 H) 4.21 (br. d, J13.90 Hz, 1 H) 5.85 (br. s., 1 H) 6.20 (s, 1 H) 7.64(br. d, J=8.40 Hz, 1 H) 7.71 (d, J=8.58 Hz, 1 H) 7.83 (br. s, 1 H) 8.56 (s, 1 H) 8.71 (s,1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With N-ethyl-N,N-diisopropylamine; In 2-methoxy-ethanol; at 120℃; | A solution of intermediate 30 (501.5 mg, 2 mmol) and <strong>[58421-79-7]4-chloro-6-methyl-quinazoline</strong>12 (535.9 mg, 3 mmol) in methoxyethanol (5 mL) was stirred at 120C overnight. Themixture was evaporated and the residue was dissolved in dichloromethane, washed twice with water, dried over Mg504, filtered and evaporated. The residue was purified over silica with dichloromethane/methanol-NH3 98/2. The corresponding fractions were evaporated and the residue was crystallized in di-isopropylether with 10%acetonitrile. The greenish precipitate was filtered off and dried in vacuum to yield intermediate 31(645 mg, 82%)mlz = 392.9 (M+H) mp: 154.2C1H NMR (400 MHz, DMSO-d6) oe ppm 1.62 - 1.81 (m, 2 H), 2.45 (s, 3 H), 2.69 (s, 2 H), 4.16 (br. s., 1 H), 5.95 (br. s., 1 H), 6.60 (s, 1 H), 7.00 (s, 1 H), 7.63 (d, J=1.6 Hz, 1 H), 7.66 - 7.79 (m, 1 H), 7.86 (s, 1 H), 8.55 (s, 1 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-ethyl-N,N-diisopropylamine; In 2-methoxy-ethanol; at 100℃; | A solution of intermediate 35 (1060 mg, 3.16 mmol), <strong>[58421-79-7]4-chloro-6-methyl-quinazoline</strong> 12 (845.7 mg, 4.73 mmol), Hunig?s base (1.1 mL, 6.32 mmol) and 2-methoxyethanol(20 mL) was stirred at 100C overnight. The mixture was evaporated and the residue was taken up in water and extracted with dichloromethane 3 times. The combined organic layer was successively dried over Mg504, filtered and evaporated. The residue waspurified over a silicagel chromatography with dichloromethane/methanol 98/2 as eluent. The corresponding fractions were evaporated to yield intermediate 36 (1400 mg,92%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With potassium carbonate; In acetonitrile; at 50℃; for 72.0h; | To a solution of intermediate 7 (0.5 g, 1.55 mmol) and intermediate 12 (0.28 g, 1.55 mmol) in CH3CN (10 ml) was added K2C03 (1.07 g, 7.77 mmol). The resulting mixturewas stirred for 72 hours at 50C. The solvent was evaporated and the residue was dissolved in CH2C12. The resulting mixture was filtered and filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: petroleum ether: ethyl acetate from 0:1 to 1:1) to yield intermediate 11(350 mg, yield: 44%). m/z = 464 (M+H). |
Tags: 58421-79-7 synthesis path| 58421-79-7 SDS| 58421-79-7 COA| 58421-79-7 purity| 58421-79-7 application| 58421-79-7 NMR| 58421-79-7 COA| 58421-79-7 structure
[ 1429782-21-7 ]
4-Chloro-2,6-dimethylquinazoline
Similarity: 0.88
[ 39576-83-5 ]
2,4-Dichloro-8-methylquinazoline
Similarity: 0.88
[ 1429782-21-7 ]
4-Chloro-2,6-dimethylquinazoline
Similarity: 0.88
[ 39576-83-5 ]
2,4-Dichloro-8-methylquinazoline
Similarity: 0.88
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Health hazards | |
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H311 | Toxic in contact with skin |
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H316 | Causes mild skin irritation |
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H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
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H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
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H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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