Diisopropylethylamine → HCID 178463566, compound

HRID 243457Notes

Reaction equation

HRID 243457 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:12]2[C:16]3[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=3[N:14]=[C:13]2[C@@H:22]([NH2:24])[CH3:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:26]1[N:34]=[CH:33][N:32]=[C:31]2[C:27]=1[N:28]=[CH:29][N:30]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:21][C:18]1[CH:19]=[CH:20][C:15]2[N:14]=[C:13]([CH:22]([NH:24][C:26]3[N:34]=[CH:33][N:32]=[C:31]4[C:27]=3[N:28]=[CH:29][NH:30]4)[CH3:23])[N:12]([CH:10]3[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:11]3)[C:16]=2[CH:17]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157768HCID 68157768, compound

Product 1

HCID 178463566HCID 178463566, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-[2-((S)-1-aminoethyl)-6-fluorobenzoimidazol-1-yl]azetidine-1-carboxylic acid tert-butyl ester (354 mg, 1.05 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (278 mg, 1.16 mmol) and DIPEA (0.41 mL, 3.18 mmol) in n-butanol (1.4 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM) to afford 377 as a white solid (214 mg, 71%). LCMS (Method K): RT 3.59 min [M+H]+ 453.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.43 (1H, s), 8.23 (1H, br s), 8.14 (1H, br s), 7.96 (1H, d, J=7.67 Hz), 7.68 (1H, dd, J=8.83, 5.02 Hz), 7.36 (1H, dd, J=9.41, 2.45 Hz), 7.11 (1H, td, J=9.29, 2.36 Hz), 5.79 (1H, br s), 5.70-5.60 (1H, m), 4.48-4.34 (2H, m), 4.31-4.19 (2H, m), 1.65 (3H, d, J=6.67 Hz), 1.44 (9H, s)

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed under reduced pressure
  3. washwashed with MeOH
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-4b7807293e454b07b47763334e648851
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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