1,1'-Carbonyldiimidazole → HCID 178501155, compound
Reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH:8]([C:11]([OH:13])=O)[CH2:7][CH2:6]1)=[O:4].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.Cl.[Cl:28][C:29]1[C:30]([CH2:35][NH2:36])=[N:31][CH:32]=[CH:33][N:34]=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:28][C:29]1[C:30]([CH2:35][NH:36][C:11]([C@H:8]2[CH2:7][CH2:6][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:10][CH2:9]2)=[O:13])=[N:31][CH:32]=[CH:33][N:34]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
A THF (370 mL) solution of 4-(methoxycarbonyl)cyclohexanecarboxylic acid (15.14 g, 81.30 mmol) and CDI (13.18 g, 81.30 mmol) was placed under a nitrogen atmosphere and stirred at 60° C. for 4 h. The reaction mixture was cooled to r.t., then, (3-chloropyrazin-2-yl)methylamine bis-hydrochloride salt (16.00 g, 73.91 mmol) and DIPEA (31.52 g, 244.00 mmol, 42.5 mL) was added. After stirring at 60° C. for 20 h, the reaction was concentrated in vacuo. The crude reaction mixture was purified by a silica gel glass column chromatography (eluted with 3:2 DCM/EtOAc) to obtain the pure desired product as a slightly yellowish creamy white powder; 1H NMR (CDCl3, 400 MHz) δ 1.43-1.65 (m, 4H), 2.01-2.14 (m, 4H), 2.25 (tt, J=12.0, 3.6 Hz, 1H), 2.34 (tt, J=11.6, 3.2 Hz, 1H), 3.68 (s, 3H), 4.70 (d, J=4.4 Hz, 2H), 6.81 (s, br, —NH), 8.32-8.36 (m, 1H), 8.46 (d, J=2.4 Hz, 1H); MS (ES+): m/z 312.17/314.12 (84/32) [MH+]; HPLC: tR=2.44 min (OpenLynx, polar—5 min).
Workup
- temperatureThe reaction mixture was cooled to r.t.
- stirringAfter stirring at 60° C. for 20 h
- concentrationthe reaction was concentrated in vacuo
- customThe crude reaction mixture
- customwas purified by a silica gel glass column chromatography (eluted with 3:2 DCM/EtOAc)
Sources & evidence
- ORD record
- ord-59343175c424493b8ad57bcb217a79fb
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08367826B2
Reaction notes
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