Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 267243-28-7 | MDL No. : | MFCD09837878 |
Formula : | C24H25ClFN5O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 485.94 | Pubchem ID : | - |
Synonyms : |
CI-1033;PD-183805
|
Num. heavy atoms : | 34 |
Num. arom. heavy atoms : | 16 |
Fraction Csp3 : | 0.29 |
Num. rotatable bonds : | 10 |
Num. H-bond acceptors : | 7.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 133.81 |
TPSA : | 88.61 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -6.5 cm/s |
Log Po/w (iLOGP) : | 4.17 |
Log Po/w (XLOGP3) : | 3.9 |
Log Po/w (WLOGP) : | 4.24 |
Log Po/w (MLOGP) : | 2.7 |
Log Po/w (SILICOS-IT) : | 4.33 |
Consensus Log Po/w : | 3.87 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -5.0 |
Solubility : | 0.00488 mg/ml ; 0.00001 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -5.46 |
Solubility : | 0.00169 mg/ml ; 0.00000348 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -8.22 |
Solubility : | 0.00000295 mg/ml ; 0.0000000061 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 3.0 |
Synthetic accessibility : | 3.48 |
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: |
* 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 |
---|---|---|
38% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl acetamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: Na / tetrahydrofuran / 2 h / 20 °C 1.2: 58 percent / tetrahydrofuran 2.1: 78 percent / Fe; aq. HOAc / ethanol / 0.5 h / Heating 3.1: 38 percent / EDCI*HCl; Et3N / N,N-dimethyl-acetamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 72 percent / CH2Cl2; propan-2-ol / 0.5 h / 20 °C 2.1: Na / tetrahydrofuran / 2 h / 20 °C 2.2: 58 percent / tetrahydrofuran 3.1: 78 percent / Fe; aq. HOAc / ethanol / 0.5 h / Heating 4.1: 38 percent / EDCI*HCl; Et3N / N,N-dimethyl-acetamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 72 percent / CH2Cl2; propan-2-ol / 0.5 h / 20 °C 2.1: Na / tetrahydrofuran / 2 h / 20 °C 2.2: 58 percent / tetrahydrofuran 3.1: 78 percent / Fe; aq. HOAc / ethanol / 0.5 h / Heating 4.1: 38 percent / EDCI*HCl; Et3N / N,N-dimethyl-acetamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: Na / tetrahydrofuran / 2 h / 20 °C 1.2: 58 percent / tetrahydrofuran 2.1: 78 percent / Fe; aq. HOAc / ethanol / 0.5 h / Heating 3.1: 38 percent / EDCI*HCl; Et3N / N,N-dimethyl-acetamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 78 percent / Fe; aq. HOAc / ethanol / 0.5 h / Heating 2: 38 percent / EDCI*HCl; Et3N / N,N-dimethyl-acetamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.9% | With trifluoroacetic acid for 6h; Heating / reflux; | 7.A Example 7; Preparation of N-[4-(3-chloro-4-fluoro-phenyl-amino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide [0141] Procedure A. N-[4-[(3-chloro-4-fluoro-phenyl)-(3,4-dimethoxy-benzyl)-amino]-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide (0.044 g, 0.069 mmol) was dissolved in trifluoroacetic acid (4 mL) then heated to reflux for 6 h. After cooling, the TFA was evaporated under reduced pressure and ethyl acetate was added. The resulting mixture was washed with dilute aqueous sodium bicarbonate. The organic layer was then washed with brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give the crude product as a yellow foam. Chromatography on a BIOTAGE 12S cartridge eluted with 10% isopropanol in methylene chloride gave N-[4-(3-chloro-4-fluoro-phenyl-amino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide (0.031 g, 92.9%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.87 (s, 1H, CONH), 9.67 (s, 1H, NH), 8.93 (s, 1H, H-5), 8.60 (s, 1H, H-2), 8.20 (dd, J=7.05, 2.5 Hz, 1H, H-2'), 7.89-7.85 (m, 1H, H-6'), 7.49 (t, J=9.0 Hz, 1H, H-5'), 7.36 (s, 1H, H-8), 6.78 (dd, J=10.2, 17.1 Hz, 1H, CHCH2), 6.38 (dd, J=1.9, 17.1 Hz, 1H, CHCH2), 5.88 (dd, J=1.9, 10.2 Hz, 1H, CHCH2), 4.34 (t, J=6.3 Hz, 2H, CH2O), 3.66 (bs, 4H, -CH2NCH2-), 2.51 (bs, 4H, -CH2OCH2-), 2.08 (bt, J=6.6 Hz, 2H, CH2CH2CH2); MS (APCI+) m/z 486.2, 488.2 (M+1). |
73.9% | With methanesulfonic acid In tetrahydrofuran at 0 - 20℃; for 4 - 5h; | 7.B [0142] Procedure B. A THF solution (50 mL approx. 0.72 M, 36.2 mmol) of N-[4-[(3-chloro-4-fluoro-phenyl)-(3,4-dimethoxy-benzyl)-amino]-7-(3-morpholin-4-yl-propoxy)-quinazolin-6 yl]-acrylamide was reduced in volume (to approx. 30 mL) under vacuum and cooled to 0-5° C. Methanesulfonic acid (46 mL, 710 mmol) was added, neat, while maintaining the temperature of the reaction mixture at <15° C. The reaction mixture was reduced in volume under vacuum at ambient temperature to approx. 60 mL and stirred at ambient temperature until all starting material was consumed (about 4-5 h). The crude product was obtained by quenching the mixture into NaOH/NaCl aq (300 mL, 3.0 M in NaOH) and filtering the resulting precipitate. The crude product was washed with water (4×25 mL) and dried overnight under a stream of N2. The crude product was recrystallized from acetone to yield N-[4-[(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6 yl]-acrylamide (13.00 g, 26.88 mmol, 73.9% from (3-chloro-4-fluoro-phenyl)-(3,4-dimethoxy-benzyl)-[7-(3-morpholin-4-yl-propoxy)-6-nitro-quinazolin-4-yl]-amine) as a slightly yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | D Step D Step D N-[4-(3-Chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide Isobutyl chloroformate (27.2 g, 0.20 mol) was added dropwise over 10 minutes to a solution of acrylic acid (14.40 g, 0.20 mol) and triethylamine (40.48 g, 0.40 mol) in THF (800 mL) stirred under nitrogen at 0° C. After a further 10 minutes, the white slurry was transferred to a-25° C. cooling bath and stirred under nitrogen for 20 minutes. 6-Amino-[(3-chloro4-fluorophenyl)amino]-7-[3-(4-morpholino)propoxy]quinazoline (43.19 g, 0.100 mol) in THF (500 mL) was added dropwise over 1.33 hours. The cooling bath was adjusted to-20° C., and after a further 2.33 hours, the reaction mixture was quenched by addition of water (100 mL) in one portion. After 20 minutes the reaction mixture was poured onto cracked ice (2 Kg), swirled, and gradually diluted with water (5 L). The mixture stood for 16 hours and was then Buchner filtered. The precipitate was rinsed with water (2*1 L), air dried for 18 hours, and then dried in a vacuum oven over P2O5 at 60° C. for 16 hours to give crude N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholino)propoxy]quinazolin-6-yl]acrylamide (35.76 g, 73% uncorrected) as a greenish-yellow solid. The mother liquors precipitated further solid which was Buchner filtered, rinsed with water (1 L), and air dried for 14 hours to give further crude product (4.73 g, 10% uncorrected) as a greenish-yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.7 mg | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0℃; for 0.5h; |
[ 179552-75-1 ]
N4-(3-Chloro-4-fluorophenyl)-7-methoxyquinazoline-4,6-diamine
Similarity: 0.87
[ 314771-76-1 ]
(S)-N4-(3-Chloro-4-fluorophenyl)-7-((tetrahydrofuran-3-yl)oxy)quinazoline-4,6-diamine
Similarity: 0.86
[ 912556-91-3 ]
N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
Similarity: 0.84
[ 869199-61-1 ]
N-(3-Chloro-4-fluorophenyl)-N-(7-methoxy-6-nitroquinazolin-4-yl)acetamide
Similarity: 0.83
[ 179552-75-1 ]
N4-(3-Chloro-4-fluorophenyl)-7-methoxyquinazoline-4,6-diamine
Similarity: 0.87
[ 314771-76-1 ]
(S)-N4-(3-Chloro-4-fluorophenyl)-7-((tetrahydrofuran-3-yl)oxy)quinazoline-4,6-diamine
Similarity: 0.86
[ 912556-91-3 ]
N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
Similarity: 0.84
[ 869199-61-1 ]
N-(3-Chloro-4-fluorophenyl)-N-(7-methoxy-6-nitroquinazolin-4-yl)acetamide
Similarity: 0.83
[ 194423-15-9 ]
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)acrylamide
Similarity: 0.58
[ 179552-75-1 ]
N4-(3-Chloro-4-fluorophenyl)-7-methoxyquinazoline-4,6-diamine
Similarity: 0.87
[ 314771-76-1 ]
(S)-N4-(3-Chloro-4-fluorophenyl)-7-((tetrahydrofuran-3-yl)oxy)quinazoline-4,6-diamine
Similarity: 0.86
[ 912556-91-3 ]
N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
Similarity: 0.84
[ 869199-61-1 ]
N-(3-Chloro-4-fluorophenyl)-N-(7-methoxy-6-nitroquinazolin-4-yl)acetamide
Similarity: 0.83
[ 179552-75-1 ]
N4-(3-Chloro-4-fluorophenyl)-7-methoxyquinazoline-4,6-diamine
Similarity: 0.87
[ 314771-76-1 ]
(S)-N4-(3-Chloro-4-fluorophenyl)-7-((tetrahydrofuran-3-yl)oxy)quinazoline-4,6-diamine
Similarity: 0.86
[ 912556-91-3 ]
N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
Similarity: 0.84
[ 869199-61-1 ]
N-(3-Chloro-4-fluorophenyl)-N-(7-methoxy-6-nitroquinazolin-4-yl)acetamide
Similarity: 0.83
[ 869199-61-1 ]
N-(3-Chloro-4-fluorophenyl)-N-(7-methoxy-6-nitroquinazolin-4-yl)acetamide
Similarity: 0.83
[ 179552-75-1 ]
N4-(3-Chloro-4-fluorophenyl)-7-methoxyquinazoline-4,6-diamine
Similarity: 0.87
[ 314771-76-1 ]
(S)-N4-(3-Chloro-4-fluorophenyl)-7-((tetrahydrofuran-3-yl)oxy)quinazoline-4,6-diamine
Similarity: 0.86
[ 912556-91-3 ]
N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
Similarity: 0.84
[ 869199-61-1 ]
N-(3-Chloro-4-fluorophenyl)-N-(7-methoxy-6-nitroquinazolin-4-yl)acetamide
Similarity: 0.83
[ 1260612-13-2 ]
(S)-2-(2-(2-Methylindolin-1-yl)-2-oxoethyl)-6-morpholinopyrimidin-4(3H)-one
Similarity: 0.53
[ 179552-75-1 ]
N4-(3-Chloro-4-fluorophenyl)-7-methoxyquinazoline-4,6-diamine
Similarity: 0.87
[ 314771-76-1 ]
(S)-N4-(3-Chloro-4-fluorophenyl)-7-((tetrahydrofuran-3-yl)oxy)quinazoline-4,6-diamine
Similarity: 0.86
[ 912556-91-3 ]
N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
Similarity: 0.84
[ 869199-61-1 ]
N-(3-Chloro-4-fluorophenyl)-N-(7-methoxy-6-nitroquinazolin-4-yl)acetamide
Similarity: 0.83