1-(Methylamino)adamantane → 3-(Difluoromethyl)-1-(5-fluoro-pyrimidin-2-yl)-1h-pyrazole-4-carboxylic acid (adamantan-1-ylmethyl)-amide

HRID 2279614Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2279614
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2C=CC=CC=2N=N1.[F:28][CH:29]([F:45])[C:30]1[C:34]([C:35]([OH:37])=O)=[CH:33][N:32]([C:38]2[N:43]=[CH:42][C:41]([F:44])=[CH:40][N:39]=2)[N:31]=1.[C:46]12(NC)[CH2:55][CH:50]3[CH2:51][CH:52]([CH2:54][CH:48]([CH2:49]3)[CH2:47]1)[CH2:53]2.CC(N(C)C)=O>CN(C=O)C>[C:46]12([CH2:12][NH:8][C:35]([C:34]3[C:30]([CH:29]([F:28])[F:45])=[N:31][N:32]([C:38]4[N:43]=[CH:42][C:41]([F:44])=[CH:40][N:39]=4)[CH:33]=3)=[O:37])[CH2:47][CH:48]3[CH2:49][CH:50]([CH2:51][CH:52]([CH2:54]3)[CH2:53]1)[CH2:55]2

Komponenten

6

Edukt 4

HCID 194761-(Methylamino)adamantaneHCID 31374DimethylacetamideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 595798213-(Difluoromethyl)-1-(5-fluoropyrimidin-2-yl)-1H-pyrazole-4-carboxylic acid

Produkt 1

HCID 595798793-(Difluoromethyl)-1-(5-fluoro-pyrimidin-2-yl)-1h-pyrazole-4-carboxylic acid (adamantan-1-ylmethyl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

BOP (98 mg, 0.22 mmol) is added to a solution of 3-(difluoromethyl)-1-(5-fluoropyrimidin-2-yl)-1H-pyrazole-4-carboxylic acid (38 mg, 0.147 mmol), admantan-1-yl-methylamine (24 mg, 0.147 mmol) and DMA (0.052 mL) in DMF (1.0 mL) at rt. The mixture is stirred for 20 h. The mixture is poured into ice water (5 mL), extracted with EtOAc (3×20 mL) and dried over anhydrous MgSO4. The crude product is purified by silica gel column chromatography using 30% EtOAc/hexane to afford the title compound as a white solid. 1H NMR (DMSO-D6): 9.45 (s, 1H), 9.05 (s, 2H), 8.35 (m, 1H), 7.29-7.36 (t, 1H), 2.93 (d, 2H), 1.91 (m, 3H), 1.47-1.65 (m, 12H). MS (M+1)=406.28; RT=1.34 min *IC50.

Aufarbeitung

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. customThe crude product is purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0739416e271d4c98a733b8d9c94f6cfb
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133204B2

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