Diisopropylethylamine → HCID 178493641, compound

HRID 243430Notes

Reaction equation

HRID 243430 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[C:21]=1[O:22][CH3:23].Cl[C:25]1[N:33]=[CH:32][N:31]=[C:30]2[C:26]=1[N:27]=[CH:28][N:29]2C1CCCCO1.CCN(C(C)C)C(C)C>CC(O)C.Cl.CO>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH:14][C:25]3[N:33]=[CH:32][N:31]=[C:30]4[C:26]=3[N:27]=[CH:28][NH:29]4)[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[C:21]=1[O:22][CH3:23]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157332(S)-1-(6-Fluoro-7-methoxy-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 178493641HCID 178493641, compoundYield 63.7%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-1-(6-fluoro-7-methoxy-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (0.16 g, 0.44 mmol) in IPA (3 mL) was added 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (139 mg, 0.58 mmol) and DIPEA (229 μL, 1.34 mmol) and the reaction mixture heated at 90° C. for 72 hours. The reaction mixture was concentrated in vacuo and the resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc) to give a white solid: LCMS (Method C): RT=3.13 min, [M+H]+=488. The solid was dissolved in HCl in methanol (1.25 M, 5 mL) and the reaction mixture stirred at RT for 10 min. The reaction mixture was concentrated in vacuo and the resultant residue subjected to prep. HPLC (C18 phenomonix column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient) to give 338 as a white solid (113 mg, 63%). 1H NMR 400 MHz δ (d6-DMSO): 8.10-8.00 (2H, m), 7.89-7.75 (1H, m), 7.66-7.29 (7H, m), 7.13-7.02 (1H, m), 5.38-5.17 (1H, m), 3.33 (3H, s), 1.48 (3H, d, J=6.8 Hz), LCMS (Method K): RT=3.40 min, [M+H]+=404

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washthe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc)
  3. customto give a white solid
  4. concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-c8d9988e0dc1479b9d8166665c1bc26c
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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