Cesium carbonate → Methyl 3-[(4-fluorobenzyl)amino]pyridine-4-carboxylate

HRID 1847142노트

반응식

HRID 1847142 반응식
Br[C:2]1[CH:11]=[N:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH2:18])=[CH:15][CH:14]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH:18][C:2]2[CH:11]=[N:10][CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:15][CH:14]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 673264-FluorobenzylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2762700Methyl 3-bromoisonicotinate

생성물 1

HCID 83322074Methyl 3-[(4-fluorobenzyl)amino]pyridine-4-carboxylate수율 88%

시약·촉매·용매 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 312751,4-Dioxane용매

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온도
116 °C

실험 절차

Methyl 3-bromoisonicotinate (220 mg, 1.02 mmol), 4-fluorobenzylamine (132 μL, 1.22 mmol), tris(dibenzylideneacetone)dipalladium(O) (47 mg, 0.051 mmol), Xantphos (89 mg, 0.153 mmol), and cesium carbonate (500 mg, 1.53 mmol) were combined in dioxane (4 mL) under N2 in a sealed microwave tube. The reaction mixture was heated at 116° C. in a microwave for 1 h. The mixture was then filtered, washing with DCM, to remove solids. The solution was concentrated in vacuo and purified by silica gel chromatography (20-50% EtOAc/hexanes) to give 228 mg (88%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.93 (d, 1H, J=5.0 Hz), 7.79 (br s, 1H), 7.63 (d, 1H, J=5.0 Hz), 7.27-7.34 (m, 2H), 7.03 (t, 2H, J=8.6 Hz), 4.47 (d, 2H, J=5.6 Hz), 3.89 (s, 3H). [M+H] calc'd for C14H13FN2O2, 261. Found 261.

후처리

  1. filtrationThe mixture was then filtered
  2. washwashing with DCM
  3. customto remove solids
  4. concentrationThe solution was concentrated in vacuo
  5. custompurified by silica gel chromatography (20-50% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-884cc055a21f45bda0fef01dde0ad0e9
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952151B2

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