Hydrochloric Acid → HCID 68157522, compound

HRID 242979Notes

Reaction equation

HRID 242979 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]([C@@H:20]([NH:22]C(OC(C)(C)C)=O)[CH3:21])=[N:10][C:9]=2[CH:8]=[CH:7][C:6]=1[F:30])=[O:4].Cl.Cl[C:33]1[N:41]=[CH:40][N:39]=[C:38]2[C:34]=1[N:35]=[CH:36][N:37]2[CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][O:43]1.CCN(C(C)C)C(C)C>CO.O1CCOCC1.C(O)CCC>[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:11]([C@@H:20]([NH:22][C:33]3[N:41]=[CH:40][N:39]=[C:38]4[C:34]=3[N:35]=[CH:36][N:37]4[CH:42]3[CH2:47][CH2:46][CH2:45][CH2:44][O:43]3)[CH3:21])=[N:10][C:9]=2[CH:8]=[CH:7][C:6]=1[F:30])=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 681579512-((S)-1-tertbutoxycarbonylaminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazole-4-carboxylic acid methyl ester

Product 1

HCID 68157522HCID 68157522, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 2-((S)-1-tertbutoxycarbonylaminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazole-4-carboxylic acid methyl ester (1.1 g, 2.7 mmol) in MeOH (20 mL) was added 4N HCl in dioxane (5 mL) and the reaction mixture was heated at 45° C. for 3 h. The volatiles were removed under reduced pressure and the resulting residue was treated with 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (825 mg, 3.46 mmol) and DIPEA (1.8 mL, 10.6 mmol) in n-butanol (10 mL). The reaction mixture was heated in a sealed vial for 16 h at 90° C. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc) to afford the title compound (1.2 g, 87%). LCMS (Method C): RT 3.11 min [M+H]+ 516.2.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. temperatureThe reaction mixture was heated in a sealed vial for 16 h at 90° C
  3. temperatureAfter cooling to RT
  4. customthe volatiles were removed under reduced pressure
  5. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-d10d3f3e15db4b89a38d7e9a632624a2
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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