Triethylamine → tert-Butyl (6-(7-(3-fluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate

HRID 1401342

Reaktionsgleichung

Reaktionsgleichung von HRID 1401342
[NH2:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[CH:4][C:3]=1[F:37].C(N(CC)CC)C.Cl[C:46]([C:48]1([C:51]([OH:53])=O)[CH2:50][CH2:49]1)=[O:47].C(N(C(C)C)CC)(C)C.[F:63][C:64]1[CH:70]=[CH:69][C:67]([NH2:68])=[CH:66][CH:65]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[F:37][C:3]1[CH:4]=[C:5]([CH:35]=[CH:36][C:2]=1[NH:1][C:46]([C:48]1([C:51](=[O:53])[NH:68][C:67]2[CH:69]=[CH:70][C:64]([F:63])=[CH:65][CH:66]=2)[CH2:50][CH2:49]1)=[O:47])[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[N:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=3)[S:15][C:8]=12

Komponenten

8

Edukt 6

HCID 8471TriethylamineHCID 97314-FluoroanilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45081290Cyclopropanecarboxylic acid, 1-(chlorocarbonyl)- (9CI)HCID 57919486tert-Butyl (6-(7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate

Produkt 1

HCID 57967259tert-Butyl (6-(7-(3-fluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamateAusbeute 61,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To aniline 20 (40 mg, 0.076 mmol, Scheme 6) and triethylamine (0.20 mL, 1.4 mmol) in THF (10 mL) at r.t. was added a solution of 63 (1.0 mL, 0.26 mmol) in THF and the resulting mixture was stirred for 3 h. The reaction mixture was then quenched with water (1.0 mL) and concentrated. The residue was partitioned between ethyl acetate and water, and the organic phase was washed with water and brine, dried (MgSO4), filtered and concentrated. The residue was dissolved in DMF (10 mL) and diisopropylethylamine (0.2 mL, 0.14 g, 1.1 mmol), 4-fluoroaniline (50 mg, 0.45 mmol), and HATU (75 mg, 0.20 mmol) were sequentially added. The mixture was stirred for 4 h at r.t. and partitioned between ethyl acetate and water. The organic phase was separated, washed with water, sat. NaHCO3, and brine, dried (MgSO4), filtered and concentrated. Silica gel chromatography of the residue (eluent ethyl acetate) provided 64 (34 mg, 61%). MS (m/z)=730.5 (M+H).

Aufarbeitung

  1. customThe reaction mixture was then quenched with water (1.0 mL)
  2. concentrationconcentrated
  3. customThe residue was partitioned between ethyl acetate and water
  4. washthe organic phase was washed with water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in DMF (10 mL)
  9. stirringThe mixture was stirred for 4 h at r.t.
  10. custompartitioned between ethyl acetate and water
  11. customThe organic phase was separated
  12. washwashed with water, sat. NaHCO3, and brine
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-b549f041e6d142c8a0734e1338e2d1cc
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08907091B2

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