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Dimethylamine → 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-N,N-dimethyl-2-oxoacetamide

HRID 245416
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 245416
[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:33]2[CH2:38][C@H:37]([CH3:39])[O:36][C@H:35]([CH3:40])[CH2:34]2)=[C:22]([F:32])[C:23]([F:31])=[C:24]([C:26](=[O:30])[C:27]([OH:29])=O)[CH:25]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:41][N:42](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:43].F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.CNC>C1COCC1.CN(C=O)C.O>[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:33]2[CH2:38][C@H:37]([CH3:39])[O:36][C@H:35]([CH3:40])[CH2:34]2)=[C:22]([F:32])[C:23]([F:31])=[C:24]([C:26](=[O:30])[C:27]([N:42]([CH3:43])[CH3:41])=[O:29])[CH:25]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
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Komponenten

8

Edukt 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866580682-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid2×

Produkt 1

HCID 86658070
2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-N,N-dimethyl-2-oxoacetamide
Ausbeute 74,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid (Intermediate 118, 250 mg, 0.44 mmol), HATU (335 mg, 0.88 mmol), triethylamine (0.184 ml, 1.32 mmol) and 2.0M dimethylamine (0.440 ml, 0.88 mmol) in THF were stirred in DMF (5 ml) in a closed vial for 16 hours. The reaction was diluted with water and extracted 3× with ethyl acetate. The organic layers were washed 3× with brine, dried over MgSO4 and concentrated to give an oil. The oil was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate. Fractions were combined and concentrated to give the title compound (195 mg, 0.328 mmol, 74.5%)

Aufarbeitung

  1. extractionextracted 3× with ethyl acetate
  2. washThe organic layers were washed 3× with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give an oil
  6. customThe oil was purified by silica gel column chromatography
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-78f41e7ef952407fb849ea102715be46
Quelldatensatz
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08658641B2

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