Diisopropylethylamine → (R)-3-(2-{(S)-1-[9-(Tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}benzoimidazol-1-yl)piperidine-1-carboxylic acid tertbutyl ester

HRID 242822Notes

Reaction equation

HRID 242822 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[C@@H:23]([NH2:25])[CH3:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:27]1[N:35]=[CH:34][N:33]=[C:32]2[C:28]=1[N:29]=[CH:30][N:31]2[CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][O:37]1.CCN(C(C)C)C(C)C>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[C@@H:23]([NH:25][C:27]2[N:35]=[CH:34][N:33]=[C:32]3[C:28]=2[N:29]=[CH:30][N:31]3[CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][O:37]2)[CH3:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157746(R)-3-[2-((S)-1-Aminoethyl)benzoimidazol-1-yl]piperidine-1-carboxylic acid tertbutyl ester

Product 1

HCID 68157943(R)-3-(2-{(S)-1-[9-(Tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}benzoimidazol-1-yl)piperidine-1-carboxylic acid tertbutyl esterYield 87%

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-3-[2-((S)-1-aminoethyl)benzoimidazol-1-yl]piperidine-1-carboxylic acid tertbutyl ester (1.65 g, 4.79 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (1.14 g, 4.79 mmol), and DIPEA (2.5 mL, 14.4 mmol) in IMS (10 mL) was stirred in a sealed vial for 48 h at 90° C. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc). The product containing fractions were concentrated in vacuo affording (R)-3-(2-{(S)-1-[9-(Tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}benzoimidazol-1-yl)piperidine-1-carboxylic acid tertbutyl ester as a white foam (2.27 g, 87%). LCMS: RT 2.88 min [M+H]+ 547.1.

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)
  4. additionThe product containing fractions
  5. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-522529f47c1244bcbf5eca62cf3ecf0e
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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