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

HRID 2373883Notes

Reaction equation

HRID 2373883 reaction equation
[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

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-09b85c3fab824d288f5053ba72bf5ae8
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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