ChemicalBook CAS DataBase List Poziotinib (HM781-36B)

Poziotinib (HM781-36B) synthesis

6synthesis methods

Product Name:Poziotinib (HM781-36B)
CAS Number:1092364-38-9
Molecular formula:C23H21Cl2FN4O3
Molecular Weight:491.34

Poziotinib (HM781-36b) is a novel oral cancer cell inhibitor for the treatment of NSCLC, breast cancer and stomach cancer.Poziotinib was synthesized by using 7- methoxy-4-oxo-3,4-dihydroquinazolin-yl acetate as starting material in 6 steps.

1429757-65-2 Synthesis

4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-ol

1429757-65-2
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1-[4-[[(4-Methylphenyl)sulfonyl]oxy]-1-piperidinyl]-2-propen-1-one

1620740-65-9
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1092364-38-9
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Yield:1092364-38-9 77%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl acetamide at 70; for 24 h;

Steps:

1.1-2 Preparation of l-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7- methoxyquinazolin-6-yloxy)piperidin-l-yl)prop-2-en-l-one, the compound of formula (I)

4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-ol (12 g, 34 mmol) prepared in Preparation Example 1, l-acryloylpiperidin-4-yl 4- methylbenzenesulfonate (16 g, 51 mmol) prepared in step (1-1), K₂CO₃ (9.4 g, 68 mmol) and dimethylacetamide (DMAc, 300 mL) were admixed. The reaction temperature was raised to 70°C, and the mixture was stirred for 24 hours. Upon completion of the reaction, the mixture was cooled down to room temperature, extracted with ethyl ester (300 mL), and then washed with water (300 mL). The organic layer was separated, and distilled under a reduced pressure. The residue thus obtained was solidified by adding ethyl ester, filtered, and dried to obtain the target compound (12.8 g, yield: 77%). 1H-NMR (300 MHz, DMSO-d₆) δ 9.65 (bs, 1H), 8.40 (s, 1H), 7.88 (s, 1H), 7.64-7.56 (m, 2H), 7.24 (s, 1H), 6.89-6.80 (m, 1H), 6.15-6.08 (m, 1H), 5.70-5.66 (m, 1H), 4.78 (m, 1H), 3.94 (s, 3H), 3.87 (m, 2H), 3.48 (m, 2H), 2.03 (m, 2H), 1.70 (m, 1H).

References:

WO2014/116070,2014,A1 Location in patent:Page/Page column 10-11

1429757-65-2 Synthesis

1429757-65-2
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