Cesium carbonate → Ethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047112노트

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HRID 1047112 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:5]2=[O:19].[CH2:20]([NH:22][C:23](=[O:43])[NH:24][C:25]1[N:30]=[CH:29][C:28](B(O)O)=[C:27]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[CH:26]=1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:12]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([C:28]3[CH:29]=[N:30][C:25]([NH:24][C:23](=[O:43])[NH:22][CH2:20][CH3:21])=[CH:26][C:27]=3[C:34]3[S:35][CH:36]=[C:37]([C:39]([F:42])([F:40])[F:41])[N:38]=3)=[CH:11][N:10]=2)[C:5](=[O:19])[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:7]1)[CH3:13]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2회HCID 68748009Ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2회

생성물 1

HCID 68747705Ethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate수율 25%

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
85 °C

실험 절차

In a round bottomed flask, ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 15, 400 mg, 1.3 mmol), 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 700 mg, 1.72 mmol) and cesium carbonate (3.78 g, 2.46 mmol) were combined and suspended in 10 mL of dioxane:water (8:2). The suspension was purged with argon for 15 min. then tetrakis (triphenylphosphine) palladium (140 mg, 0.2 mmol) was added under argon atmosphere and the reaction mixture was heated to 80-90° C. for 5 h. After completion of the reaction, the reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure to a residue, to which acetonitrile was added. The precipitated solid was filtered and dried to afford 150 mg (25%) of ethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate.

후처리

  1. customThe suspension was purged with argon for 15 min.
  2. customAfter completion of the reaction
  3. temperaturethe reaction mixture was cooled to room temperature
  4. filtrationfiltered through celite
  5. concentrationThe filtrate was concentrated under reduced pressure to a residue, to which acetonitrile
  6. additionwas added
  7. filtrationThe precipitated solid was filtered
  8. customdried

출처 및 근거

ORD 기록
ord-b37a76790c104171ba89297c5c90c0b9
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569484B2

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