1-Methylcyclopropanecarboxylic acid → N-((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-yl)-1-methylcyclopropanecarboxamide

HRID 1098914Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1098914
[CH3:1][C:2]1([C:5]([OH:7])=O)[CH2:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[O:41]1[CH2:46][CH2:45][O:44][C:43]2[CH:47]=[C:48]([C@@H:51]([O:55][C:56]3[CH:57]=[C:58]4[C:62](=[CH:63][CH:64]=3)[N:61]([C:65]3[CH:70]=[CH:69][C:68]([F:71])=[CH:67][CH:66]=3)[N:60]=[CH:59]4)[C@@H:52]([NH2:54])[CH3:53])[CH:49]=[CH:50][C:42]1=2>CN1C(=O)CCC1.O>[O:41]1[CH2:46][CH2:45][O:44][C:43]2[CH:47]=[C:48]([C@@H:51]([O:55][C:56]3[CH:57]=[C:58]4[C:62](=[CH:63][CH:64]=3)[N:61]([C:65]3[CH:66]=[CH:67][C:68]([F:71])=[CH:69][CH:70]=3)[N:60]=[CH:59]4)[C@@H:52]([NH:54][C:5]([C:2]3([CH3:1])[CH2:4][CH2:3]3)=[O:7])[CH3:53])[CH:49]=[CH:50][C:42]1=2

Komponenten

7

Edukt 4

HCID 813261-Methylcyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59339888(1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine

Produkt 1

HCID 59339637N-((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-yl)-1-methylcyclopropanecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel2×

Versuchsvorschrift

1-methylcyclopropanecarboxylic acid (39 mg, 0.39 mmol), HATU (150 mg, 0.39 mmol) and DIPEA (170 μl, 0.97 mmol) in NMP (2 mL) was stirred at r.t. for 5 min until a solution had formed. To this solution was added (1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine (19a) (102 mg, 0.24 mmol) dissolved in NMP (1 mL). The reaction mixture was stirred for 2 h at r.t. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×10 mL), the organic phases was then washed with brine, dried over Na2SO4, filtered and evaporated. The remaining oily residue was purified by HPLC. Fractions containing product was freezedried. Yield 68 mg (55%10).

Aufarbeitung

  1. customhad formed
  2. extractionextracted with EtOAc (2×10 mL)
  3. washthe organic phases was then washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe remaining oily residue was purified by HPLC
  8. additionFractions containing product
  9. customwas freezedried

Quellen und Nachweise

ORD-Eintrag
ord-8040761119874179969bd8907e52cd3c
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143290B2

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