Aluminium lithium hydride → HCID 178508462, compound

HRID 386166Notes

Reaction equation

HRID 386166 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([NH2:20])[C:14]3=[C:13]([C:21]3[CH:30]=[C:29]4[C:24]([CH:25]=[CH:26][C:27]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)=[N:28]4)=[CH:23][CH:22]=3)[N:12]=2)[CH2:7][CH2:6]1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[NH2:20][C:19]1[C:14]2[N:15]([C:11]([C@H:8]3[CH2:7][CH2:6][C@H:5]([CH2:3][OH:2])[CH2:10][CH2:9]3)=[N:12][C:13]=2[C:21]2[CH:30]=[C:29]3[C:24]([CH:25]=[CH:26][C:27]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[N:28]3)=[CH:23][CH:22]=2)[CH:16]=[CH:17][N:18]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 178501047HCID 178501047, compound

Product 1

HCID 178508462HCID 178508462, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A THF solution (8 mL) of trans-4-[8-amino-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methyl ester was cooled to −78° C. and charged with 1M LiAlH4 in THF (1.5 mL, 1.5 mmol) dropwise; the reaction vessel was removed from the −78° C. cooling bath and stirred at rt for 4 h. The reaction mixture was charged with EtOAc, Na2SO4.10H2O, and silica gel and concentrated in vacuo to yellow solids. The crude material was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 1%˜7N NH3 in MeOH/CH2Cl2] to afford the desired product as a yellow solid; 1H NMR (CDCl3, 400 MHz) δ 1.17-1.29 (m, 2H), 1.63-1.73 (m, 2H), 1.87-2.07 (m, 4H), 2.12-2.23 (m, 2H), 2.92-3.02 (m, 1H), 3.56 (d, 2H, J=6.0 Hz), 5.25 (s, 2H), 7.13 (d, 1H, J=4.8 Hz), 7.27-7.28 (m, 1H), 7.46-7.50 (m, 1H), 7.52-7.57 (m, 2H), 7.89-7.96 (m, 3H), 8.18-8.21 (m, 2H), 8.27 (d, 1H, J=8.8 Hz), 8.40-8.42 (m, 1H); MS (ES+): m/z 450.0 [MH+]; HPLC: tR=2.4 min (Micromass Platform H, polar—5 min).

Workup

  1. customthe reaction vessel was removed from the −78° C.
  2. temperaturecooling bath
  3. additionThe reaction mixture was charged with EtOAc, Na2SO4.10H2O, and silica gel
  4. concentrationconcentrated in vacuo to yellow solids
  5. customThe crude material was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 1%˜7N NH3 in MeOH/CH2Cl2]

Sources & evidence

ORD record
ord-6dfcf3dc26824a0f84a4bc271c4a9324
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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