Aluminium lithium hydride → HCID 178508462, compound

HRID 1163115Notes

Reaction equation

HRID 1163115 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 −780C 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 II, 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-4b168add20ac491b84811b9371c0824b
Source dataset
uspto-grants-2010_10
Patent number
US07820662B2

Reaction notes

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