1,2-Dichloroethane → {3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

HRID 2373883Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2373883
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([NH:23]C(C2CC(=C)C2)=O)[C:16]2[C:21](Cl)=[N:20][CH:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:32]([O:39]C1C=C(C(N)C2C(Cl)=NC=CN=2)C=CC=1)[C:33]1[CH:38]=[CH:37][CH:36]=C[CH:34]=1.CC[N:57](C(C)C)C(C)C.C=C1CC(C(O)=O)C1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.C(OCC)(=O)C>[NH2:57][C:21]1[C:16]2[N:17]([C:36]([CH:37]3[CH2:34][CH:33]([CH2:32][OH:39])[CH2:38]3)=[N:23][C:15]=2[C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)[CH:18]=[CH:19][N:20]=1

Komponenten

9

Edukt 6

HCID 111,2-DichloroethaneHCID 274753-Methylenecyclobutanecarboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 598527683-Methylenecyclobutanecarboxylic acid [(3-benzyloxyphenyl)-(3-chloropyrazin-2-yl)methyl]amideHCID 86604615C-(3-benzyloxyphenyl)-C-(3-chloropyrazin-2-yl)methylamine hydrochloride

Produkt 1

HCID 11406927{3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

3-Methylenecyclobutanecarboxylic acid [(3-benzyloxyphenyl)-(3-chloropyrazin-2-yl)methyl]amide: To a suspension of C-(3-benzyloxyphenyl)-C-(3-chloropyrazin-2-yl)methylamine hydrochloride (724 mg, 2.0 mol) in methylene dichloride (10 mL) was added iPr2NEt (1.7 mL, 10.0 mmol), at which time the solid dissolved. The reaction was charged with 3-methylenecyclobutanecarboxylic acid (560 mg, 5.0 mmol), EDC (1.15 g, 6.0 mmol) and HOBt (270 mg, 2.0 mmol) and the resulting mixture was stirred at rt overnight. The mixture was diluted with ethyl acetate (50 mL), washed with sat. aq. NaHCO3 (2×20 mL) and brine (2×20 mL), and dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, and the crude material was purified by silica gel column chromatography (eluting with hexanes:EtOAc=80:20→60:40), yielding the title product as a light-yellow viscous oil; MS (ES, Pos.): m/z 420/422 (3/1) [MH+]; 1H NMR (CDCl3, 400 MHz) δ 2.85-3.09 (m, 5H), 4.78 (m, 2H), 5.03 (s, 2H), 6.55 (d, J=7.9 Hz, 1H), 6.87-6.95 (m, 3H), 7.08 (br d, 1H, NH), 7.21-7.41 (m, 6H), 8.33 (d, J=2.5 Hz, 1H), 8.49 (d, J=2.5 Hz, 1H).

Aufarbeitung

  1. dissolutionat which time the solid dissolved
  2. washwashed with sat. aq. NaHCO3 (2×20 mL) and brine (2×20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe crude material was purified by silica gel column chromatography (eluting with hexanes:EtOAc=80:20→60:40)

Quellen und Nachweise

ORD-Eintrag
ord-09b85c3fab824d288f5053ba72bf5ae8
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07459554B2

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