1,2-Dichloroethane → HCID 178485733, compound

HRID 386165Notes

Reaction equation

HRID 386165 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:27]3[CH2:32][CH2:31][C@H:30]([C:33](O)=[O:34])[CH2:29][CH2:28]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.Cl.CN.C[CH2:40][N:41](C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[CH3:40][NH:41][C:33]([C@H:30]1[CH2:31][CH2:32][C@H:27]([C:8]2[N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]3=[C:10]([C:11]3[CH:20]=[C:19]4[C:14]([CH:15]=[CH:16][C:17]([C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=5)=[N:18]4)=[CH:13][CH:12]=3)[N:9]=2)[CH2:28][CH2:29]1)=[O:34]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 6364545Methylamine hydrochlorideHCID 178508463HCID 178508463, compound

Product 1

HCID 178485733HCID 178485733, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A DMF solution (3 mL) of trans-4-[8-amino-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid (260 mg, 0.56 mmol) and methylamine hydrochloride (379 mg, 5.6 mmol) in a sealed tube was charged with DIEA (0.98 mL, 5.6 mmol), 0.6M HOAt in DMF (0.93 mL, 0.56 mmol), and then EDC (161 mg, 0.84 mmol). The reaction mixture stirred at it for 16 h. The reaction mixture was concentrated to solids, taken up in CH2Cl2, charged with silica, and concentrated to brown solids. The crude material was purified by silica gel column chromatography [Jones Flashmaster, 5 g/25 mL cartridge, eluting with 2%˜7N NH3 in MeOH/CH2Cl2]. The purified material was recrystallized from MeOH/CH2Cl2/diethyl ether to the desired product as a light yellow solid; 1H NMR (DMSO-d6, 400 MHz) δ 1.56-1.73 (m, 4H), 1.85-1.91 (m, 2H), 2.01-2.06 (m, 2H), 2.17-2.25 (m, 1H), 2.52 (d, 3H, J=4.4 Hz), 3.12-3.20 (m, 1H), 6.17 (s, 2H), 7.09 (d, 1H, J=4.8 Hz), 7.51-7.59 (m, 4H), 7.73 (d, 1H, J=4.8 Hz), 7.90 (dd, 1H, J=2.0 Hz, 8.4 Hz), 8.09 (d, 1H, J=8.4 Hz), 8.18 (d, 1H, J=8.8 Hz), 8.23 (s, 1H), 8.30 (d, 2H, J=7.6 Hz), 8.51 (d, 1H, J=8.4 Hz); MS (ES+): m/z 477.0[MH+]; HPLC: tR=2.1 min (Micromass Platform II, polar—5 min).

Workup

  1. concentrationThe reaction mixture was concentrated to solids
  2. additioncharged with silica
  3. concentrationconcentrated to brown solids
  4. customThe crude material was purified by silica gel column chromatography [Jones Flashmaster, 5 g/25 mL cartridge, eluting with 2%˜7N NH3 in MeOH/CH2Cl2]
  5. customThe purified material was recrystallized from MeOH/CH2Cl2/diethyl ether to the desired product as a light yellow solid
  6. customHPLC: tR=2.1 min (Micromass Platform II, polar—5 min)

Sources & evidence

ORD record
ord-3f0ba30ac87f4d2e8e66134822d8433b
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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