1,2-Dichloroethane → HCID 178485733, compound

HRID 244088Notes

Reaction equation

HRID 244088 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 rt 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-810e8f25ece841eaa5fc13be280b130b
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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