Aluminium lithium hydride → HCID 178461453, compound

HRID 449067Notes

Reaction equation

HRID 449067 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@@H:24]3[CH2:27][C@H:26]([CH2:28]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:25]3)=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1.[NH4+].[Cl-]>[CH3:28][C@@H:26]1[CH2:27][C@H:24]([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:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[N:9]=2)[CH2:25]1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 178427762HCID 178427762, compound

Product 1

HCID 178461453HCID 178461453, compound

Reagents, catalysts & solvents 2

HCID 25517Ammonium ChlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of cis-toluene-4-sulfonic acid 3-[8-amino-1-(4-phenoxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutylmethyl ester (20.0 mg, 0.0370 mmol) in THF (1 mL) at −78° C. was added 1.0 M of LiAlH4 in THF (0.15 mL), and the mixture was allowed to warm to rt. Once the reaction was complete, a few drops of sat. NH4Cl was added to quench. The material was transferred to a separatory funnel, and extracted using DCM and sat. NaHCO3. The aqueous layer was washed twice with DCM, and the organic fractions were combined and concentrated in vacuo. The material was dissolved in minimal MeOH/DCM, and loaded onto a prep TLC plate, eluting with 2% (7N NH3 in MeOH)/DCM. The band containing the product was collected, and the material was filtered off by washing with 1:1 MeOH I DCM. The filtrate was concentrated in vacuo to afford the title compound. 1H NMR (400 MHz, CDCl3): δ=1.14 (d, J=6.3 Hz, 3H), 2.13-2.23 (m, 2H), 2.46-2.57 (m, 1H), 2.58-2.67 (m, 2H), 3.52-3.62 (m, 1H), 5.07 (br. s., 2H), 7.02-7.10 (m, 3H), 7.10-7.18 (m, 4H), 7.35-7.41 (m, 2H), 7.61-7.66 (m, 2H). MS (ES+): m/z 371.06 (100) [MH+]. HPLC: tR=2.67 min (polar—5 min).

Workup

  1. customto quench
  2. customThe material was transferred to a separatory funnel
  3. extractionextracted
  4. washThe aqueous layer was washed twice with DCM
  5. concentrationconcentrated in vacuo
  6. dissolutionThe material was dissolved in minimal MeOH/DCM
  7. washeluting with 2% (7N NH3 in MeOH)/DCM
  8. additionThe band containing the product
  9. customwas collected
  10. filtrationthe material was filtered off
  11. washby washing with 1:1 MeOH I DCM
  12. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-da633d1eee484293889cc378be4be4a4
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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