Hydrochloric Acid → HCID 68157183, compound

HRID 243112Notes

Reaction equation

HRID 243112 reaction equation
C[O:2][C:3]([C:5]1[C:13]2[N:12]([CH:14]3[CH2:16][CH2:15]3)[C:11]([C@@H:17]([NH:19][C:20]3[N:28]=[CH:27][N:26]=[C:25]4[C:21]=3[N:22]=[CH:23][N:24]4[CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][O:30]3)[CH3:18])=[N:10][C:9]=2[CH:8]=[CH:7][C:6]=1[F:35])=[O:4].O[Li].O.Cl>CO.O>[CH:14]1([N:12]2[C:13]3[C:5]([C:3]([OH:4])=[O:2])=[C:6]([F:35])[CH:7]=[CH:8][C:9]=3[N:10]=[C:11]2[C@@H:17]([NH:19][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][N:24]3[CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[CH3:18])[CH2:15][CH2:16]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrate2×HCID 68157700HCID 68157700, compound

Product 1

HCID 68157183HCID 68157183, compoundYield 21.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 3-cyclopropyl-5-fluoro-2-{(S)-1-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid methyl ester (607 mg, 1.27 mmol) and LiOH.H2O (266 mg, 6.33 mmol) in MeOH (20 mL) and water (2 mL) was heated at 80° C. for 22 h. Additional LiOH.H2O (266 mg) was added and the mixture heated at 80° C. for 5 h. After cooling to RT, the pH of the mixture was adjusted to 4 by addition of 1M aqueous HCl. The organic solvent was removed under reduced pressure and the aqueous phase extracted with EtOAc. The organic fraction was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in DCM) to afford the title compound (127 mg, 21% over 2 steps) as a white solid. LCMS (Method C): RT 2.17 min [M+H]+ 466.22.

Workup

  1. temperatureAfter cooling to RT
  2. customThe organic solvent was removed under reduced pressure
  3. extractionthe aqueous phase extracted with EtOAc
  4. washThe organic fraction was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-8163afe8bab24f3fa97e6b13dc6d7801
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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