Dimethylformamide → tert-butyl N-[(1R)-1-[[2-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxypyrimidin-5-yl]carbamoyl]propyl]carbamate

HRID 527624Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 527624
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([CH2:13][CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].CN(C=O)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:44][C:45]1[C:50]2[O:51][CH2:52][C:53]3([CH2:55][CH2:54]3)[C:49]=2[C:48]([O:56][C:57]2[N:62]=[CH:61][C:60]([NH2:63])=[CH:59][N:58]=2)=[CH:47][CH:46]=1>>[CH3:44][C:45]1[C:50]2[O:51][CH2:52][C:53]3([CH2:55][CH2:54]3)[C:49]=2[C:48]([O:56][C:57]2[N:58]=[CH:59][C:60]([NH:63][C:10]([C@H:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13][CH3:14])=[O:12])=[CH:61][N:62]=2)=[CH:47][CH:46]=1

Komponenten

5

Edukt 4

HCID 6228DimethylformamideHCID 2755936(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 679602052-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxypyrimidin-5-amine2×

Produkt 1

HCID 86698450tert-butyl N-[(1R)-1-[[2-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxypyrimidin-5-yl]carbamoyl]propyl]carbamateAusbeute 53,5 %

Versuchsvorschrift

To a solution of (2R)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)butanoic acid (45 mg, 0.222 mmol) in dry DMF (1 ml) DIPEA (870, 0.5 mmol) and then HATU (80 mg, 0.21 mmol) were added and the reaction mixture was stirred for 15 minutes at r.t. 2-(7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-yl)oxypyrimidin-5-amine (Intermediate 162, 50 mg, 0.185 mmol) was then added and the reaction mixture was stirred for 6 hours at room temperature. The reaction was quenched with water (2 ml) diluted with brine (5 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 90:10 to cyclohexane/ethyl acetate 60:40 as eluents affording the title compound (45 mg) as a white solid.

Aufarbeitung

  1. stirringthe reaction mixture was stirred for 6 hours at room temperature
  2. customThe reaction was quenched with water (2 ml)
  3. additiondiluted with brine (5 ml)
  4. extractionextracted with ethyl acetate (2×10 ml)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 90:10 to cyclohexane/ethyl acetate 60:40 as eluents

Quellen und Nachweise

ORD-Eintrag
ord-cf177913100e4d199afbd40ca668308c
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346790B2

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