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Trimethylamine → 2-(2-fluoro-phenyl)-4-(5-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-pyridin-3-yl)-[1,8]naphthyridine

HRID 1404303
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HRID 1404303 반응식
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[O:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[O:31][CH2:32][CH2:33][N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1.CC1(C)C(C)(C)OB(C2C=NNC=2)O1.ClC1C=CC(F)=C(C2C=C(C3C=NC=C(C4C=NN(CCN5CCCC5)C=4)C=3)C3C(=NC=CC=3)N=2)C=1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C>COCCOC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:10]1[CH:9]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:37]3[CH:36]=[N:35][N:34]([CH2:33][CH2:32][O:31][CH:26]4[CH2:27][CH2:28][CH2:29][CH2:30][O:25]4)[CH:38]=3)[CH:3]=2)[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1
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참가 물질

9

반응물 6

HCID 1146TrimethylamineHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 18407952Tripotassium phosphate trihydrateHCID 53344959HCID 53344959, 화합물HCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 682645484-(5-Bromo-pyridin-3-yl)-2-(2-fluoro-phenyl)-[1,8]naphthyridine

생성물 1

HCID 673805632-(2-fluoro-phenyl)-4-(5-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-pyridin-3-yl)-[1,8]naphthyridine

시약·촉매·용매 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A slurry of 380 mg (1.00 mmol) 4-(5-bromo-pyridin-3-yl)-2-(2-fluoro-phenyl)-[1,8]naphthyridine, 354 mg (1.10 mmol) 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (prepared from 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole and 2-(2-bromo-ethoxy)-tetrahydro-pyran (in analogy to example 10) and 425 mg (2.00 mmol) tri-potassium-phosphate-trihydrate in 3 ml 1,2-dimethoxyethane was heated to 85° C. under nitrogen. Then 35.1 mg (0.05 mmol) bis-(triphenylphosphine)-palladium(II)-chloride and 14 μl trimethylamine were added. The reaction mixture was stirred for 16 hours at 85° C. The reaction mixture was cooled to room temperature and partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding 2-(2-fluoro-phenyl)-4-(5-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-pyridin-3-yl)-[1,8]naphthyridine as yellow solid; HPLC-MS: 2.13 min, [M+H] 496.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between water and dichloromethane
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. customevaporated
  5. customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent

출처 및 근거

ORD 기록
ord-e65db05d7c20441489b4220cbf963087
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08912216B2

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