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Diisopropylethylamine → HCID 25099552, 화합물

HRID 2381917
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HRID 2381917 반응식
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1.CN(C(SC1[N+]([O-])=CC=CC=1)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:48][C:49]1[CH:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[N:54]([NH2:58])[CH2:53][C:52]2([CH3:60])[CH3:59]>CN(C=O)C.O.CCOC(C)=O>[F:48][C:49]1[CH:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[N:54]([NH:58][C:8]([C:7]1[C:2]([CH3:1])=[N:3][C:4]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[N:5][CH:6]=1)=[O:10])[CH2:53][C:52]2([CH3:60])[CH3:59]
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참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 10571248(Dimethylamino)-N,N-dimethyl((1-oxo-1lambda~5~-pyridin-2-yl)sulfanyl)methaniminium hexafluorophosphateHCID 457912394-Methyl-2-(pyridin-3-yl)pyrimidine-5-carboxylic acidHCID 68555288HCID 68555288, 화합물

생성물 1

HCID 25099552HCID 25099552, 화합물수율 53%

시약·촉매·용매 3

HCID 962Water용매
HCID 6228Dimethylformamide용매
HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

A solution of 4-methyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid (706 mg, 3.28 mmol), HOTT (1.34 g, 3.6 mmol), and DIPEA (1.65 mL, 9.45 mmol) in DMF (15 mL) is stirred at rt under N2 for 10 min. 5-Fluoro-3,3-dimethyl-2,3-dihydro-indol-1-ylamine (560 mg, 3.11 mmol) is added. The resulting mixture is stirred at 80° C. overnight. The mixture is cooled and portioned between EtOAc and water. The organic phase is separated, washed with saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 35% EtOAc in heptane to afford 4-methyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid (5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-amide (617 mg, 53%) as a solid. MS: 378 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 10.44 (s, 1H), 9.55-9.54 (m, 1H), 9.01 (s, 1H), 8.77-8.75 (m, 1H), 8.72-8.68 (m, 1H), 7.60 (dd, 1H), 7.06 (dd, 1H), 6.96-6.88 (m, 1H), 6.76-6.72 (m, 1H), 3.51 (s, 2H), 2.70 (s, 3H), 1.33 (s, 6H).

후처리

  1. temperatureThe mixture is cooled
  2. customThe organic phase is separated
  3. washwashed with saturated aqueous NaHCO3, water and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with 35% EtOAc in heptane

출처 및 근거

ORD 기록
ord-e87e01937d61452ba1c162fc8f622bb0
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08258130B2

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