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Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 4-Fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(pyrimidin-4-yl)-cyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide

HRID 1672076
ノート
印刷プレビュー

反応式

HRID 1672076 の反応式
[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[CH3:31])[C:25]([OH:27])=O.Cl.[N:33]1[CH:38]=[CH:37][C:36]([C:39]2([NH2:42])[CH2:41][CH2:40]2)=[N:35][CH:34]=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[C:7]2[C:8]([C:18]([NH:19][CH3:20])=[O:21])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[CH:23]=[C:24]([C:25](=[O:27])[NH:42][C:39]2([C:36]3[CH:37]=[CH:38][N:33]=[CH:34][N:35]=3)[CH2:41][CH2:40]2)[CH:28]=[CH:29][C:30]=1[CH3:31]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 592756803-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 672924411-(Pyrimidin-4-yl)cyclopropan-1-amine hydrochloride

生成物 1

HCID 534682484-Fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(pyrimidin-4-yl)-cyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 3-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.050 g, 0.114 mmol, 1.0 eq), 1-(pyrimidin-4-yl)cyclopropanamine HCl (0.015 g, 0.113 mmol, 1.0 eq) in DMF at 0° C. was added TEA (0.060 g, 0.594 mmol, 5.0 eq) and BOP reagent (0.076 g, 0.172 mmol, 1.5 eq). The reaction mixture was stirred at RT overnight. The reaction mixture was diluted with water and extracted with EtOAc. the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative HPLC. Yield: 0.035 g (57.37%). 1H NMR (400 MHz, CD3OD): δ 9.00 (d, J=1.2 Hz, 1H), 8.60 (d, J=5.6 Hz, 1H), 7.98-7.90 (m and dd, 3H), 7.85 (d, J=2.0 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.51-7.49 (two overlapping d, 2H), 7.35-7.28 (m, 3H), 2.96 (s, 3H), 2.30 (s, 3H), 1.84-1.81 (m, 2H), 1.52-1.49 (m, 2H). 19F NMR (376.57 MHz, CD3OD): δ−76.94 (TFA), −112.22, −122.76 LCMS: (ES+) m/z=539.2 (M+H)+

後処理

  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 preparative HPLC

出典と根拠

ORDレコード
ord-19096e332a894ab8a3cf5896c6dc406e
出典データセット
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07994171B2

反応ノート

読み込み中…

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