1-Hydroxybenzotriazole → N-(2-hydroxy-2-methylpropyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-9-carboxamide

HRID 1498182Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1498182
[CH:1]([N:4]1[C:8]([C:9]2[CH:10]=[C:11]3[N:17]([N:18]=2)[C:16]2[CH:19]=[C:20]([C:23](O)=[O:24])[CH:21]=[CH:22][C:15]=2[O:14][CH2:13][CH2:12]3)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[NH2:69][CH2:70][C:71]([CH3:74])([OH:73])[CH3:72]>CN(C=O)C>[OH:73][C:71]([CH3:74])([CH3:72])[CH2:70][NH:69][C:23]([C:20]1[CH:21]=[CH:22][C:15]2[O:14][CH2:13][CH2:12][C:11]3[N:17]([N:18]=[C:9]([C:8]4[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=[CH:6][N:7]=4)[CH:10]=3)[C:16]=2[CH:19]=1)=[O:24]

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 951022-Propanol, 1-amino-2-methyl-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582047582-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene-9-carboxylic acid

Produkt 1

HCID 68355376N-(2-hydroxy-2-methylpropyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-9-carboxamideAusbeute 67,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene-9-carboxylic acid (0.2 g, 0.59 mmol) was suspended in DMF (5 mL) and DIPEA (0.21 mL, 1.2 mmol) added. The resultant solution was treated with HATU (0.23 g, 0.6 mmol) and HOBT (81 mg, 0.6 mmol) before the addition of 1-amino-2-methyl-propan-2-ol (52.5 mg, 0.59 mmol) then stirred for 18 h at RT. The reaction mixture was concentrated in vacuo and the resultant residue partitioned between DCM and water. The aqueous layer was extracted three times with DCM and the combined organic extracts washed with water, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% MeOH in ethyl acetate) and recrystallistion from ethyl acetate to give 116 (163 mg, 67%). 1H NMR (CDCl3, 400 MHz): δ 8.46 (d, J=2.2 Hz, 1 H); 7.94 (s, 1 H); 7.72 (dd, J=8.4, 2.2 Hz, 1 H); 7.22 (d, J=8.4 Hz, 1 H); 6.86 (s, 1 H); 6.66 (s, 1 H); 5.74-5.61 (m, 1 H); 4.57 (t, J=5.7 Hz, 2 H); 3.50 (d, J=5.9 Hz, 2 H); 3.22 (t, J=5.7 Hz, 2 H); 2.18 (s, 1 H); 1.59 (d, J=6.6 Hz, 6 H); 1.31 (s, 6 H). LCMS: RT=9.53 min, M+H+=411

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe resultant residue partitioned between DCM and water
  3. extractionThe aqueous layer was extracted three times with DCM
  4. washthe combined organic extracts washed with water
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-4c627451bcb444dcba0b0f05f9983b81
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09198918B2

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