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

반응식

HRID 15333 반응식
[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

참가 물질

7

반응물 4

HCID 166371768-Bromo-2,3-dihydro-1,4-benzodioxine-6-carbaldehydeHCID 22047174Furo[2,3-c]pyridin-5-ylmethanolHCID 57486873HCID 57486873, 화합물HCID 68566554Carbamic acid, [(3R,4S)-3-fluoro-4-piperidinyl]-, phenylmethyl ester, rel-(-)-

생성물 1

HCID 68685415Racemic methyl 2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-[(cis)-3-fluoro-4-({[(phenylmethyl)oxy]carbonyl}amino)-1-piperidinyl]propanoate수율 100%

시약·촉매·용매 2

HCID 664601,1,3,3-Tetramethylguanidine촉매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-721d8cceaacc48fea2c0ccf5e6db4a4c
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732461B2

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