8-Bromo-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde → Racemic methyl 2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-[(cis)-3-fluoro-4-({[(phenylmethyl)oxy]carbonyl}amino)-1-piperidinyl]propanoate

HRID 15333

Reaction equation

[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[C:12](=[CH2:17])[C:13]([O:15][CH3:16])=[O:14])=[N:9][C:8]([O:18][CH3:19])=[CH:7][CH:6]=2.[C:20]1([CH2:26][O:27][C:28](=[O:37])[NH:29][C@H:30]2[CH2:35][CH2:34][NH:33][CH2:32][C@H:31]2[F:36])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.BrC1C2OCCOC=2C=C(C=O)C=1.O1C2=CN=C(CO)C=C2C=C1>CN(C)C(N(C)C)=N.CN(C=O)C>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([CH2:17][N:33]1[CH2:34][CH2:35][C@H:30]([NH:29][C:28]([O:27][CH2:26][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[O:37])[C@H:31]([F:36])[CH2:32]1)[C:13]([O:15][CH3:16])=[O:14])=[N:9][C:8]([O:18][CH3:19])=[CH:7][CH:6]=2

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of methyl 2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-2-propenoate (953 mg, 3.63 mmol), cis-phenylmethyl[3-fluoro-4-piperidinyl]carbamate Enantiomer 2 (for a synthesis see WO2004058144, prepared by analogy to Examples 142(b), (c) and (d) from the Enantiomer 2 of Example 142(a)) (1.1 g, 4.35 mmol) and 1,1,3,3-tetramethylguanidine (6 drops) in DMF (3.5 ml) was heated at 80° C. under argon for 3 hours, cooled and evaporated. Chromatography, eluting with 1% methanol/dichloromethane, gave the product in 100% yield.

Workup

temperaturecooled
customevaporated
washChromatography, eluting with 1% methanol/dichloromethane
customgave the product in 100% yield

Sources & evidence

ORD record: ord-721d8cceaacc48fea2c0ccf5e6db4a4c
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07732461B2

Linked notes

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