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Dimethylphosphinic acid → [6-({3-(Aminocarbonyl)-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridin-2-yl]methyl dimethylphosphinate

HRID 386035
ノート
印刷プレビュー

反応式

HRID 386035 の反応式
[F:1][C:2]1[CH:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[C:12]1[S:16][C:15]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][OH:25])[N:19]=2)=[C:14]([C:26]([NH2:28])=[O:27])[CH:13]=1.[CH3:29][P:30]([CH3:33])(=O)[OH:31].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH3:29][P:30]([CH3:33])(=[O:31])[O:25][CH2:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([NH:17][C:15]2[S:16][C:12]([C:3]3[CH:4]=[CH:5][C:6]([C:8]([OH:11])([CH3:9])[CH3:10])=[CH:7][C:2]=3[F:1])=[CH:13][C:14]=2[C:26]([NH2:28])=[O:27])[N:19]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 76777Dimethylphosphinic acid2 回HCID 81531Diisopropylethylamine2 回HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate2 回HCID 516892Sodium BicarbonateHCID 251234855-(2-Fluoro-4-(1-hydroxy-1-methylethyl)phenyl)-2-((6-(hydroxymethyl)-2-pyridinyl)amino)-3-thiophenecarboxamide

生成物 1

HCID 59526131
[6-({3-(Aminocarbonyl)-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridin-2-yl]methyl dimethylphosphinate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

5-[2-Fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[6-(hydroxymethyl)pyridin-2-yl]amino}thiophene-3-carboxamide (Example 43) (125 mg, 0.31 mmol), dimethylphosphinic acid (32.2 mg, 0.34 mmol), BOP (207 mg, 0.47 mmol) and DIPEA (48.3 mg, 0.37 mmol) were stirred in DMF (1 mL) at room temperature for 6 hours. Additional dimethylphosphinic acid (11.71 mg, 0.13 mmol), BOP (68.9 mg, 0.16 mmol) and DIPEA (0.033 mL, 0.19 mmol) were added and the reaction mixture was maintained at room temperature overnight. Saturated sodium bicarbonate was added and the mixture was extracted with EtOAc (×5). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by silica gel column chromatography (0-10% MeOH-EtOAc) gave the title compound as a pale yellow solid.

後処理

  1. extractionthe mixture was extracted with EtOAc (×5)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by silica gel column chromatography (0-10% MeOH-EtOAc)

出典と根拠

ORDレコード
ord-e16c62da5f6a4451b55e85ad9b0be557
出典データセット
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08367706B2

反応ノート

読み込み中…

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