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

HRID 595276ノート

反応式

HRID 595276 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-55bcbfd5b6cd4363a6896e79c3cf970f
出典データセット
uspto-grants-2016_01
特許番号
US09242984B2

反応ノート

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