Acetonitrile → 4-Amino-3-chloro-5-fluoro-6-(4-chloro-2-fluoro-3-methoxy-phenyl)picolinonitrile

HRID 882009

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HRID 882009 반응식
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]#[N:11])[C:3]=1[Cl:12].[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B2OCCCO2)=[C:16]([F:26])[C:15]=1[O:27][CH3:28].[F-].[K+].C(#N)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:17]2[CH:18]=[CH:19][C:14]([Cl:13])=[C:15]([O:27][CH3:28])[C:16]=2[F:26])[N:5]=[C:4]([C:10]#[N:11])[C:3]=1[Cl:12]

참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 522689Potassium FluorideHCID 577824192-(4-Chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinaneHCID 71551457HCID 71551457, 화합물

생성물 1

HCID 704956694-Amino-3-chloro-5-fluoro-6-(4-chloro-2-fluoro-3-methoxy-phenyl)picolinonitrile수율 57.2%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매

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온도
75 °C

실험 절차

A mixture of 4-amino-3,6-dichloro-5-fluoropicolinonitrile (0.37 g, 1.80 mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinane (0.549 g, 2.24 mmol) and KF (0.209 g, 3.59 mmol) was taken into acetonitrile (6.75 mL) and water (2.25 mL). The mixture was stirred and sparged with a nitrogen atmosphere. Pd(PPh3)2Cl2 (63 mg, 0.1 mmol) was added, and the mixture was again sparged with nitrogen. The solution was then heated to 75° C. under nitrogen for 2 h. Upon cooling down, a precipitate formed and was collected by filtration, washed with water and dried under vacuum to give the product (0.34 g) as an off-white solid. The aqueous phase was extracted with EtOAc (3×), and the combined organic extracts were washed with brine, dried, and concentrated. Purification by silica gel chromatography gave additional product (0.12 g) as a white solid. Total yield 78%. 1H NMR (400 MHz, DMSO-d6) δ 7.50 (dd, J=8.5, 1.4 Hz, 1H), 7.45 (s, 2H), 7.33 (dd, J=8.5, 7.2 Hz, 1H), 3.94 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 152.97 (d, J=253.2 Hz), 145.73 (d, J=260.8 Hz), 143.82 (d, J=13.7 Hz), 141.83 (d, J=14.7 Hz), 138.45 (d, J=14.8 Hz), 133.93-132.79 (m), 128.93 (d, J=3.3 Hz), 127.74 (s), 126.37-125.10 (m), 122.08 (dd, J=13.6, 3.9 Hz), 119.34 (d, J=4.5 Hz), 114.99 (s), 61.61 (s); 19F NMR (376 MHz, DMSO-d6) δ −129.00 (dd, J=28.2, 7.0 Hz, 1F), −133.76 (d, J=28.2 Hz, 1F); ESIMS m/z 330.1 ([M+H]+).

후처리

  1. customsparged with a nitrogen atmosphere
  2. customthe mixture was again sparged with nitrogen
  3. temperatureUpon cooling down
  4. customa precipitate formed
  5. filtrationwas collected by filtration
  6. washwashed with water
  7. customdried under vacuum

출처 및 근거

ORD 기록
ord-2ed4b79da5d24ca3b22339e2c3492735
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993772B2

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