Binap, (A+-)- → 6-Bromo-N-[4-(1-fluoroethyl)-2-pyridinyl]-4-methyl-2-pyridinamine

HRID 595276노트

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HRID 595276 반응식
[F:1][CH:2]([C:4]1[CH:9]=[CH:8][N:7]=[C:6](I)[CH:5]=1)[CH3:3].[Br:11][C:12]1[N:17]=[C:16]([NH2:18])[CH:15]=[C:14]([CH3:19])[CH:13]=1.CC([O-])(C)C.[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Br:11][C:12]1[N:17]=[C:16]([NH:18][C:6]2[CH:5]=[C:4]([CH:2]([F:1])[CH3:3])[CH:9]=[CH:8][N:7]=2)[CH:15]=[C:14]([CH3:19])[CH:13]=1

참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-HCID 221765076-Bromo-4-methylpyridin-2-amineHCID 23665647Potassium tert-butoxideHCID 1182089034-(1-Fluoroethyl)-2-iodopyridine

생성물 1

HCID 901351346-Bromo-N-[4-(1-fluoroethyl)-2-pyridinyl]-4-methyl-2-pyridinamine

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
90 °C

실험 절차

4-(1-Fluoroethyl)-2-iodopyridine (90 g, 359 mmol, 1.05 equiv), 6-bromo-4-methylpyridin-2-amine (63.7 g, 341 mmol, 1.00 equiv), toluene (900 mL), t-BuOK (57.6 g, 1.50 equiv), BINAP (10.8 g, 17.3 mmol, 0.05 equiv) and Pd2(dba)3 (15.7 g, 17.1 mmol, 0.05 equiv) were combined into a 2000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen. The reaction mixture was stirred overnight at 90° C. in an oil bath and then cooled to r.t, diluted with DCM (500 mL). The solid was filtered out, washed with DCM and the filtrate was concentrated under vacuum. The residue was purified by column chromatography on silica gel column (1:15 ethyl acetate/petroleum ether) to afford 6-bromo-N-[4-(1-fluoroethyl)pyridin-2-yl]-4-methylpyridin-2-amine as a light yellow solid. ESI calc'd for C13H14BrFN3 [M+H]+ 309. found 309. 1H NMR (CD3OD, 400 MHz, ppm): δ 8.23-8.22 (m, 1H), 7.66 (s, 1H), 7.45 (s, 1H), 6.934-6.91 (m, 2H), 5.72-5.51 (m, 1H), 2.32 (s, 3H), 1.68-1.61 (m, 3H).

후처리

  1. custompurged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperaturecooled
  4. additiondiluted with DCM (500 mL)
  5. filtrationThe solid was filtered out
  6. washwashed with DCM
  7. concentrationthe filtrate was concentrated under vacuum
  8. customThe residue was purified by column chromatography on silica gel column (1:15 ethyl acetate/petroleum ether)

출처 및 근거

ORD 기록
ord-55bcbfd5b6cd4363a6896e79c3cf970f
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242984B2

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