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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
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HRID 386035 반응식
[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
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참가 물질

7

반응물 5

HCID 76777Dimethylphosphinic acid2회HCID 81531Diisopropylethylamine2회HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate2회HCID 516892Sodium BicarbonateHCID 251234855-(2-Fluoro-4-(1-hydroxy-1-methylethyl)phenyl)-2-((6-(hydroxymethyl)-2-pyridinyl)amino)-3-thiophenecarboxamide

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e16c62da5f6a4451b55e85ad9b0be557
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08367706B2

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