ChemicalBook CAS DataBase List TAK-733

TAK-733 synthesis

13synthesis methods

Product Name:TAK-733
CAS Number:1035555-63-5
Molecular formula:C17H15F2IN4O4
Molecular Weight:504.23

1035555-51-1 Synthesis

(R)-3-(2,3-DIHYDROXYPROPYL)-5-(2-FLUORO-4-IODOPHENYLAMINO)-8-METHYLPYRIDO[2,3-D]PYRIMIDINE-4,7(3H,8H)-DIONE

1035555-51-1
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1035555-63-5
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Yield: 33%

Reaction Conditions:

with Selectfluor in N,N-dimethyl-formamide;acetonitrile at 20; for 0.166667 h;

Steps:

18
Example 18: (i?)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8- methylpyrido[2,3-d]pyrimidine-4,7(3/f,8H)-dione; To a solution of (i?)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)- 8-methylpyrido[2,3-d]pyrimidine-4,7(3/f,8H)-dione (example 6) (1 g, 2.06 mmol, 1 eq) in DMF (19 mL) was added dropwise a mixture of Selectfluor (801 mg, 2.26 mmol, 1.1 eq) in acetonitrile (9 niL) and DMF (5 niL) at ambient temperature while stirring under nitrogen. The reaction mixture was stirred for 10 minutes at ambient temperature and filtered. The filtrate was purified by preparatory LC/MS (30-55% CH₃CN in H₂O) to give (i?)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8- methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 18) as an off-white solid. The recovered starting material was subjected to the same reaction conditions to produce a second crop of product. The total yield of product was 347 mg (33% yield). ¹H NMR (400 MHz, DMSO-J₆) δ ppm 3.36 - 3.40 (m, 1 H) 3.43 - 3.50 (m, 1 H) 3.58 (s, 3 H) 3.61 - 3.72 (m, 1 H) 3.72 - 3.82 (m, 1 H) 4.27 - 4.37 (m, 1 H) 4.78 - 4.87 (m, 1 H) 5.14 (d, J=5.81 Hz, 1 H) 6.93 - 7.03 (m, 1 H) 7.53 (d, J=8.84 Hz, 1 H) 7.65 - 7.74 (m, 1 H) 8.52 (s, 1 H) 10.25 (d, J=LOl Hz, 1 H). [M+H] calc'd for Ci₇Hi₅F₂IN₄O₄, 505; found, 505.

References:

TAKEDA PHARMACEUTICAL COMPANY LIMITED WO2008/79814, 2008, A2 Location in patent:Page/Page column 122-123