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Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 2-(4-Fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyrimidin-4-yl)cyclopropyl carbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

HRID 1672072
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HRID 1672072 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[C:22]([CH3:32])=[CH:23][C:24]([O:30][CH3:31])=[C:25]([CH:29]=4)[C:26](O)=[O:27])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.Cl.[N:34]1[CH:39]=[CH:38][C:37]([C:40]2([NH2:43])[CH2:42][CH2:41]2)=[N:36][CH:35]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:29]=[C:25]([C:26](=[O:27])[NH:43][C:40]5([C:37]6[CH:38]=[CH:39][N:34]=[CH:35][N:36]=6)[CH2:42][CH2:41]5)[C:24]([O:30][CH3:31])=[CH:23][C:22]=4[CH3:32])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:4][CH:3]=1
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참가 물질

6

반응물 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 592756045-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acidHCID 672924411-(Pyrimidin-4-yl)cyclopropan-1-amine hydrochloride

생성물 1

HCID 595051442-(4-Fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyrimidin-4-yl)cyclopropyl carbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (0.096 g, 0.221 mmol, 1.0 eq), 1-(pyrimidin-4-yl)cyclopropanamine HCl (0.03 g, 0.221 mmol, 1.0 eq) in DMF at 0° C. was added TEA (0.12 g, 1.188 mmol, 5.0 eq) and BOP reagent (0.146 g, 0.330 mmol, 1.5 eq). The reaction mixture was stirred as RT overnight. The reaction mixture was diluted with water, extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel (60-120) column chromatography using 3% MeOH/CHCl3 as eluent. Yield: 0.070 g (57.33%). 1H NMR (400 MHz, CD3OD): δ 8.99 (d, J=1.0 Hz, 1H), 8.61 (d, J=5.6 Hz, 1H), 7.99-7.93 (m, 2H), 7.79 (s, 1H), 7.69-7.54 (m, 3H), 7.39-7.23 (m, 3H), 7.16 (s, 1H), 4.08 (s, 3H), 2.96 (s, 3H), 2.34 (s, 3H), 1.85-1.82 (m, 2H), 1.61-1.49 (m, 2H).

후처리

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel (60-120) column chromatography

출처 및 근거

ORD 기록
ord-adaa94b7a03e4368b5479b82f7e3e5d9
출처 데이터셋
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07994171B2

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