(2S,4R)-4-methoxy-pyrrolidine-2-carboxylic acid amide → (2S,4R)-1-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)-4-methoxypyrrolidine-2-carboxamide

HRID 1629445Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1629445
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21](O)[N:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6](C)=[N:5]1)([CH3:3])[CH3:2].[CH3:25][O:26][C@H:27]1[CH2:31][NH:30][C@H:29]([C:32]([NH2:34])=[O:33])[CH2:28]1>O>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[N:20][C:21]([N:30]5[CH2:31][C@H:27]([O:26][CH3:25])[CH2:28][C@H:29]5[C:32]([NH2:34])=[O:33])=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Komponenten

4

Edukt 2

HCID 67050845(2S,4R)-4-methoxy-pyrrolidine-2-carboxylic acid amideHCID 178432612HCID 178432612, Verbindung

Produkt 1

HCID 58204938(2S,4R)-1-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepin-9-yl)-4-methoxypyrrolidine-2-carboxamideAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

Following the procedure for Examples 339 and 408, 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol and (2S,4R)-4-methoxy-pyrrolidine-2-carboxylic acid amide were reacted. The reaction mixture was diluted with water passed down an SCX-2 cartridge, washed with DCM, ethyl acetate and methanol and products eluted with 2M ammonia in methanol. Appropriate fractions were concentrated in vacuo and the resultant residue was triturated in diethyl ether and methanol, filtered and dried to give 407 as beige solid (45 mg, 32%). LCMS: RT=2.60 min, [M+H]+=439. 1H NMR 400 MHz (CDCl3) δ: 9.27 (1 H, s), 7.83 (1 H, s), 7.57 (1 H, s), 6.79 (1 H, br, s), 6.00 (1 H, s), 5.98 (1 H, m), 5.29 (1 H, br, s), 4.65 (1 H, dd, J=8.28, 4.87 Hz), 4.49-4.47 (2 H, m), 4.39-4.34 (2 H, m), 4.23 (1 H, t, J=5.53 Hz), 3.74 (1 H, dd, J=10.34, 5.70 Hz), 3.51-3.46 (1 H, m), 3.36 (3 H, s), 2.52-2.51 (1 H, m), 2.24-2.23 (1 H, m), 1.55-1.54 (6 H, m)

Aufarbeitung

  1. customwere reacted
  2. washwashed with DCM, ethyl acetate and methanol and products
  3. washeluted with 2M ammonia in methanol
  4. concentrationAppropriate fractions were concentrated in vacuo
  5. customthe resultant residue was triturated in diethyl ether
  6. filtrationmethanol, filtered
  7. customdried

Quellen und Nachweise

ORD-Eintrag
ord-5a20383b420049de9cedee6fb8493b04
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785626B2

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